a quantum-chemical dft approach to elucidation of the

Research ArticleA Quantum-Chemical DFT Approach to Elucidation ofthe Chirality Transfer Mechanism of the EnantioselectiveSuzukindashMiyaura Cross-Coupling Reaction

Radomir JasiNski1 Oleg M Demchuk2 and Dmytro Babyuk3

1 Institute of Organic Chemistry and Technology Cracow University of Technology Warszawska 24 31-155 Cracow Poland2Department of Organic Chemistry Maria Curie-Skłodowska University 33 Gliniana Street 20-614 Lublin Poland3Institute of Biology Chemistry and Bioresources Chernivtsi National University 2 Kotsyubynsky Str Chernivtsi 58012 Ukraine

Correspondence should be addressed to Oleg M Demchuk olehdemchukumcslublinpl

Received 15 February 2017 Accepted 27 March 2017 Published 25 May 2017

Academic Editor Maria F Carvalho

Copyright copy 2017 Radomir Jasinski et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

The DFT calculations of the simplified model of the asymmetric SuzukindashMiyaura coupling reaction were performed at theM062xLANL2DZ theory level at first It was found that enantioselective reactions mediated by the palladium complexes of chiralCP-ligands follow a four-stage mechanism similar to that proposed previously as one of the most credible mechanisms It shouldbe underlined that the presence of substituents in the substrates and the chiral ligand at ortho positions determines the energiesof possible diastereoisomeric transition states and intermediates in initial reaction steps This suggests that in practice a sharpselection of theoretically possible paths of chirality transfer from the catalyst to the product should have a place and therefore theabsolute configuration of the formed atropisomeric product is defined and can be predicted

1 Introduction

Palladium mediated cross-coupling reactions constitute oneof themain synthetic tools for creation of new carbon-carbonbonds [1 2] The carbon atoms of all types of hybridisationpossessing a variety of leaving or nonpreactivated groups canbe connected together if properly designed catalysts are usedExcellent chemical yields are usually observed in a majorityof cross-coupling reactions even those run under mild con-ditionsThe notable progress observed during the last decadein medicinal [3ndash6] material [7ndash10] and green chemistry[11 12] makes the issue of efficient asymmetric synthesisof drug precursors functional materials and fine chemicalssignificantly urgent since chiral nonracemic compoundshave already found wide industrial application Among allcross-coupling reactions only the asymmetric Heck coupling(and its several modifications eg the Fujiwara-Moritanireaction and oxidative boron Heck-type reactions) is welldeveloped [13ndash15] At the same time the enantioselective

approach to other coupling reactions still remains challeng-ing [16ndash18] Without clear understanding of the mechanismof chirality transfer from the chiral catalyst to the producta rational design of an efficient catalyst tailored for a givenenantioselective coupling reaction remains not possible andconsequent testing of a large quantity of similar ligands willbe a costly alternative [18 19]

Herein we are going to present the results of our com-putational finding of the origin of asymmetric inductionin cross-coupling reactions Since aryl-aryl bond formingcross-couplings are mechanistically quite similar in ourstudies on enantioselective coupling we concentrated onthe SuzukindashMiyaura reaction which is usually applied as amethod of first choice The mechanics of the nonstereocon-trolled SuzukindashMiyaura (and a few other couplings) reactioncatalysed by complexes of nonchelatingmonophosphines hasbeen studied in detail (Scheme 1) [20ndash29] and can be extrap-olated to reactions catalysed by transition metal complexesof different types and to stereoselective transformations At

HindawiJournal of ChemistryVolume 2017 Article ID 3617527 12 pageshttpsdoiorg10115520173617527

2 Journal of Chemistry

Ar

X

ArAr X

Reductiveelimination

Transmetallation

Oxidativeaddition

n = 1 2

n

n

+H

X = Hal OT

Ar1

Ar1

Ar

[PdIILn ]

[PdIIL ]

Ar1-B(OH)3 Ar

1-B(OH)2⊖

B(OH)3X

[Pd0L ] [Pd0

L4]

L = R3P R3N C=C A

⊖

O⊖

minus(4 minus n)L

f

r

Scheme 1 Generally accepted mechanism of SM reaction

the same time the nature of chirality transfer still remainsunclear and only general intuitivemechanistic considerationshave been published to date [30]

In highly enantioselective SuzukindashMiyaura couplingspalladium complexes of significantly sterically hindered lig-ands are usually used [16 18] Accurate computer calcu-lations of such large complexes need an extremely largecomputational cost Additionally for palladium catalystsbased on regular bidentate ligands (eg BINAP (I) [31])and monodentate ligands (eg oligo-aryl phosphine (II) andoligo-aryl phosphonites (III) [32]) (Figure 1) several differentmodels of solvation and mono- and biscomplexation shouldbe evaluated [23 33ndash36] Obviously a discovery of subtleinteractions influencing the absolute configuration of theproduct formed in the reaction mediated by interconvertingcomplexes of large phosphorus ligands cannot be accuratebecause of many entropic issues that certainly take place butare difficult to handle In the case of less bulky and especiallybisphosphine chelating ligands different types of 14-electronPdL2 complexes have been postulated as active catalysts andcorresponding products of the oxidative addition reactionsto such complexes have been characterised [37ndash40]Thus wedecided to concentrate on highly efficient also in asymmetricSM reactions chiral ligands of the CP-type of complexationrepresented by KenPhos and similar ones (IV) [30 41 42]MeO-MOP (V) [43] and BisNap-Phos (VI) [44] (Figure 1)These ligands form well-defined bidentate mono-P-ligandedPd(0) species [45ndash48] with the structures formally corre-sponding to the 12-electron Pd-P(III) active catalysts of theSM reaction (Scheme 2 AC) The active catalyst is extremelyreactive and readily undergoes oxidative addition reactionwith aromatic halides to form intermediates with a well-defined structure I1 [49 50]

Even such simple complexes are spatially developed andcomplicated enough not to allow accurate computation oftheir fine properties and stereochemical behaviour if theentire structure is considered Nevertheless in the case ofcatalytic systems in which substrates and ligands do notbear bending function groups (whose interaction can con-trol the geometry of preordination intermediates) and thecatalyst is a complex of the CP-ligand the geometry of theintermediates is less sensitive to the substitution pattern andseveral coordinal simplifications can be applied Thus thegeometry of the palladium complexes will remain almost thesame if the cyclohexyl groups situated on the phosphorusatom are replaced with methyl groups Also the biarylcore of the ligand can be simplified to formally chiral 621015840-dimethylbiphenyl and eventually 2-bromotoluene and 2-tolylboronic acid can be selected as the simplest substrates ofthe enantioselective cross-coupling reaction (Scheme 3)Thissignificant simplification allows accurate DFT calculationsof the entire reactions leading to the chiral (but with lowracemisation energy) product [51]

With the objective of gaining insight into the originof stereoselectivity of the selected reacting system run inaqueous media we decided to perform DFT simulationsof possible reaction paths to confirm its actual molecularmechanismandfind conditions influencing the configurationof the chiral product formed

2 Results and Discussion

21 Computational Procedure The quantum-chemical cal-culations reported in this paper were performed on ldquoZeusrdquoand ldquoPrometheusrdquo supercomputers in the ldquoCyfronetrdquo com-putational centre in Cracow The M062x [52] functional

Journal of Chemistry 3

I

Me

Me

Me

Me

Me

OMe

Me

G

II

IIIO

OP

IV V

MeO O

VI

R = Ph Cy

PPh2

PPh2

PPh2

G = PPh2

G =

NMe2

PR2

PCy120784

Figure 1 Selected chiral ligands used in SM reactions

Pd S

S = weakly coordinating solvent

Pd Pd+S

minusS Ar-Hal

Pd Ar

Hal

AC I1

fast

PC

PR2PR2PR2PR2

Scheme 2 Models of CP-complexation precatalyst PC active catalyst AC and intermediate I1

implemented in the GAUSSIAN 09 package [53] was usedThis functional is dedicated for precise energetic considera-tions [52 54] and has been recently applied for simulationof the reaction paths of several different reactions includ-ing arylic systems [55] phosphorus compounds [56] andhalogenide-derivatives [57 58] Critical structures are fullyoptimized using basis sets 6-31G(d) for H C O B Br and Pas well as LANL2DZ with one f function for Pd and withoutpseudopotential Identical basis sets have been recently usedfor quantitative description of similar processes involvingsimilar chemical molecules [21] For elementary reaction in

which anionic species are involved calculations using basisset with one diffusion function were performed in parallelto procedure described above It was found that in this waypractically identical critical structures were obtained Nextwe have reoptimized key representative transition statesusing M06 functional in which HF exchange contribution issignificantly lower than on the case of M062x functional Ithas been found that obtained structures are very similar tothose derived from M062x calculations Thus we concludedthat the applied theory level should be recognized as whollyadequate to solve the presented problem


Me

Br

Pd

Me

Me

Me

Me

Me

OH

OHOH

1

2 3

Me

Me

Pd

2

Me

Me

Pd

120784998400

PMe2 PMe2

PMe2

B⊖

-Brminus

-B(OH)3

Scheme 3 Model coupling reaction

The Berny algorithm was applied for optimization ofthe structure of the reactants and the reaction productsFirst-order saddle points were localized using the QST2procedure Stationary points were characterised by frequencycalculations All reactants and products had positive Hessianmatrices All transition states showed only one negativeeigenvalue in their diagonalized Hessian matrices and theirassociated eigenvectors were confirmed to correspond to themotion along the reaction coordinate under (IRC) calcula-tions performed to connect previously computed transitionstructures (TS) with suitable minima For the calculationsof the solvent effect (presence of water) the polarizablecontinuum model (PCM) [59] in which the cavity is createdvia a series of overlapping spheres was used For optimizedstructures thermochemical data for the temperature 119879 =298K and pressure 119901 = 1 atm were computed using vibra-tional analysis data

22 Catalyst Activation According to the widely acceptedconcept monoliganded coordinatively unsaturated andunstable 12-electron palladium complexes which are formedby dissociation of bulky diphosphine (or similar) complexescan be an active catalysts of the cross-coupling reaction(Scheme 1) In the case of CP-complexes 12-electron activecatalyst is formed by dissociation of the Pd-C coordinationbond (Scheme 2) and the energy of this process mayinfluence the reaction rate Several products of the oxidativeaddition possessing only one ligand at the phosphorus atomhave been obtained and characterised [35 36 50 60ndash62]Thus we decided to shed light on the energetic stabilityof the model chiral catalytic complex 2 (Scheme 3) The

M062x calculations showed that the complex with ldquocyclicrdquoconformation (2) is more than 55 kcalmol stable than thecompetitive structure with ldquoextendedrdquo conformation (21015840)This is a consequence of failure of the Pd-C complexationeffect in 21015840

Subsequently we performed a similar study for a similarfluorinated system illustrated in Figure 2 (structures 2a and2a1015840) in which the aryl system has a relatively more 120587-deficient nature In both cases we reached a qualitativelysimilar conclusion Thus it can be assumed that the C-Pd complexation effect is important for stabilization of thepalladium-ligand complex irrespective of the nature of thesubstitution of aryl moiety

A possible way to evaluate the Pd-C binding energy isldquohomolytic dissociationrdquo (Figure 3) of the optimized complexstructure into frozen fragments (no optimization is donefor them) The uM062xLANL2DZ calculation shows thatthe following fragmentation requires energy (1198641) equal to12997 kcalmol (Figure 3(a)) It includes Pd-Ar and Ar-Ar binding energies To exclude the Ar-Ar energy similarfragmentation is needed (Figure 3(b)) In this case thedissociation energy (1198642) is equal to 12416 kcalmol Thedifference 1198641 minus 1198642 = 581 kcalmol is due to Pd-C bindingwhich is close to the value derived by rotating theAr-Ar groupleading to 21015840 The total stabilization due to the presence ofthe Pd atom calculated similarly by removal of the Pd atomfrom the complex is 3236 kcalmol Similarly the energy ofPd-P binding was calculated to be equal to 1516 kcalmolSince the Pd-C interaction is significantly weaker than thePd-P one we expect dissociation of Pd-P within the catalyticcycle


P

Pd

2a

PMe

Me

Pd

F

F

F

F

F

F

F

FMe Me

MeMe

MeMe

120784a998400

Figure 2 ldquoCyclicrdquo (2a) and ldquoextendedrdquo (2a1015840) conformations of the fluorinated CP-complex

Pd

2

Me

Me Me

Pd

+

MePMe2

PMe2

(a)

MeMe

MeMe+

PMe2

PMe2

(b)

Figure 3 ldquoHomolytic dissociationrdquo of CP-complex 2 (a) and respective phosphine ligand (b)

23 Oxidative Addition Step Next we carried out a detailedstudy of the mechanism of model cross-coupling involvingcatalyst 2The first stage includes formation of an adduct of 2-bromotoluenewith catalyst 2 (Scheme 4) Since the palladiumatom is shielded with the aromatic ring the attack of the2-bromotoluene molecule on the Pd atom may take placeonly from directions that are not shielded by the ligand Inparticular four competitive paths were found during whichthe following processes take place (1) creation of a Pd-Brbond in the direction of the axis of the P-Pd coordinationbond (paths leading to adducts 5a and 5b resp) or (2)creation of a Pd-Br bond in the direction perpendicular tothe axis of the P-Pd bond (paths leading to adducts 5c and5d resp)

Thermodynamical analysis shows that in the case of allthe considered paths the reaction equilibrium is evidentlyshifted towards the valley of the products However 5cand 5d are relatively more stable Free Gibbs enthalpy offormation is below 29 kcalmol for these compounds andequal to ca 19 kcalmol for products 5a and 5b Generally

thermodynamic stability of theoretically possible productsshould be ordered as follows 5c gt 5d≫ 5b gt 5a

Analyses of the kinetic aspects of the directions of sub-strate transformations indicate that the reaction proceedingaccording to path C is evidently kinetically favoured (Δ119866 == 02 kcalmol) Other paths should be considered asunfavourable or outright forbidden from the kinetic point ofview (Figure 4)

The theoretically possible transformations between iso-meric adducts 5andashd have also been analysed It was found thatunder reaction conditions all of these transitions should beconsidered as forbidden from the kinetic point of view sincein all of the considered cases the interconversion energy washigher than 30 kcalmol

Thus it should be assumed that an isomer that is formedaccording to path C can be treated as a generally favouredstructure for a wide group of reactions This product entersthe subsequent addition stages

Two new bonds are formed within the transition state ofthe 1 + 2rarr 5c reactionmdashPd-Br (119903 = 3246 A) and Pd-C(Ar)


Br

Pd 1

2

Me

Me

MeMe

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Pd

Br

Pd Br

Pd

Br

5a

5b

Pd Br

5c

5d

PMe2

PMe2

PMe2

PMe2PMe2

Scheme 4 Theoretically possible product of the oxidative addition step

minus5

minus15

Reaction coordinate

minus10

minus25

minus20

minus35

minus30

5

2

1

5a

5b

5d

5c

Pd

MeMe

MeBr

PMe2

ΔG

(kca

lmol

)

Pd

Pd

Me

Me

MeMe

MeMe

Br

Br

PMe2

PMe2

Pd

PdMe

MeMe

Me

MeMe Br

Br

PMe2

PMe2

ΔGakt = 29 kcalmol

ΔGr = minus193 kcalmol

ΔGakt = 27 kcalmol


ΔGakt = 14 kcalmol


ΔGakt = 02 kcalmol


Figure 4 Energy profiles for competitive channels of oxidative addition reaction

(119903 = 2305 A) This is accompanied by the breakage of theBr-C(Ar) bond (119903 = 1981 A)

In addition to our theoretical studies the relevance ofstructure 5c can be confirmed by comparison of our theoreti-cal considerations with the X-ray structures of similar CP-palladium complexes (VII) [63 64] and additionally withthe same structure optimized using the M062xLANL2DZ

theory level in simulated presence of water (VII1015840) as shownin Figure 5 and Table 1 It was found that the key angles andinteratomic distances were rather similar

24 Transmetallation Step The different possibilities oftransmetallation reaction that may take place in the secondstage of the asymmetric SM reaction were assessed It has


P Pd12 3

CyCy

MeO

MeO

Br

Pri

Pri

Pri

Figure 5 X-ray structure of complex VII [63]

PPd

Bra

b

BO

OHOH

6Me

MeMe

Me

Me

Me

Me

BO

OHOH

6

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

H

7

Scheme 5 Two possible paths of transmetallation

Table 1 Comparison of the key geometrical parameters of com-plexes 5c VII and VII1015840

ParameterP

Pd

123

BrAr

CyCy

5c VII VII1015840

119903Pd-P [A] 2417 2407 2266119903P-C1 [A] 1871 1834 1877AngleC2-C3-Pd [

∘] 10317 10608 10673AngleC3-Pd-P [

∘] 6473 8371 8115AnglePd-P-C1 [

∘] 11388 10635 10519

been shown that the transmetallation step in a typical SMcoupling reaction does not proceed without the nucleophilicadditive which enhances the electron density at the boronatom through its coordination and formation of boron-ateadduct [20 21 24 65 66] In an aqueous solution of inor-ganic bases the role of this nucleophile may be played by

the hydroxyl anion Thus the second stage of the reac-tion includes substitution of the bromine atom with theArB(OH)3

minus anion (6) (Scheme 5) The alternative reactionpathways involving the participation of neutral ArB(OH)2 orPd-OH species were not favourable

Attack of molecule 6 on the Pd atom is possible onlywhen both methyl groups bound to phenyl rings are turnedopposite to the anion approach trajectory attack accordingto the ldquoardquo trajectory (Scheme 5) All attempts at findingtransition stages related to the theoretically possible processof the approach of molecule 6 to the Pd atom along the ldquobrdquotrajectory failed

During the approach to the Pd atom the 6 anion maytheoretically assume various orientations Two paths of suchan approach were found differing in the orientation of themethyl group within the anion However only one of theseshould be considered kinetically permitted The activationbarrier of the transition is 41 kcalmol This process takesplace via the TS2 transition state (Figures 6 and 7) The Pd-Br bond (119903 = 2696 A) of this state becomes gradually moreloose and at the same time a new Pd-O bond (119903 = 2178 A) isformed Conversion of the reacting system along the reactioncoordinate leads directly from TS2 to the product 7

During the transmetallation stage a boric acid moleculeis eliminatedwith simultaneous formation of a bondbetween


Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP

Figure 6 Views of transition states according to DFT calculations

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3

Scheme 6 Formation of the transition stage TS3

the palladium atom and the carbon atom of the phenyl ringintroduced into the reacting system from the ArB(OH)3

minus

moleculeThis transformation takes place through the transition

state TS3 (Scheme 6) and requires the activation barrier Δ119866 == 71 kcalmol to be overcome As a result of a synchronouscircular electron shift within TS3 the bonds between thepalladium atom and the oxygen atom (119903 = 2151 A) andbetween the boron atom and the carbon atom in position1 of the phenyl ring become ruptured (119903 = 1632 A) This

is accompanied by formation of a new 120590-bond between thephenyl ring and the palladium atom (119903 = 2676 A) It leads toformation of compound 8

25 The Reductive Elimination Stage The last reductiveelimination stage takes place via the TS4 transition state andrequires an activation barrier which is equal to 86 kcalmolThermodynamic factors on the other hand favour practicallyan irreversible shift of equilibrium towards the product asfree enthalpy of the system decreases by over 25 kcalmol as


minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)

Figure 7 Free Gibbs energy profile for energetically preferred reaction path according to DFT calculations

a result of this elementary reaction Notably the previouslyproposed possibility of the rotation of aryls around the Pd-Arand Pd-Ar1015840 bonds in 8 [30] whichmay yield products with anopposite absolute configuration has a rotation barrier greaterthan 15 kcalmol Thus this could be considered as almostforbidden and slow hence the product configuration changeat this stage of the reaction cannot be significant

3 Conclusions

The DFT calculations performed with the simplified reac-tion model indicate that the palladium-catalysed process ofasymmetric cross-coupling should take place according toa four-stage mechanism It should also be stated that the

presence of substituents in the ortho positions of the sub-strates (aryl bromide and borate anion) determines a sharpselection of theoretically possible reaction directions Thismeans that in practice the conversion of the reacting systemshould take place according to a single reaction path onlyBecause rupture of existing bonds takes place simultane-ously with formation of new bonds within all transitionstates the entire process should take place stereoselectivelyand lead predominantly to one atropisomeric form Thisassumption makes the task of rationalisation of the stereo-chemical outcome of the reaction much simpler since onlyone that is the first reaction stage should be analysed topredict the absolute configuration of a majority of formedbiaryl products


Conflicts of Interest

The authors declare that they have no conflicts of interest

Acknowledgments

The generous allocation of computing time by the RegionalComputer Centre ldquoCyfronetrdquo in Cracow (Grant no MNiSWZeus_lokalniePK0092013) and support from the PolishNational Science Centre (NCN Grant no 201205BST500362) are gratefully acknowledged

References

[1] A J Burke andC SMarques EdsCatalytic ArylationMethodsFrom the Academic Lab to Industrial Processes Wiley-VCHWeinheim Germany 2015

[2] L-N He E Lokteva C Mota and P Tundo Eds ChemistryBeyond Chlorine Springer Basel Switzerland 2016

[3] G-Q Lin Q-D You and J-F Cheng Eds Chiral DrugsChemistry and Biological Action John Wiley amp Sons HobokenNJ USA 2011

[4] L A Nguyen H He and C Pham-Huy ldquoChiral drugs anoverviewrdquo International Journal of Biomedical Science vol 2 pp85ndash100 2006

[5] J McConathy and M J Owens ldquoStereochemistry in drugactionrdquoThe Primary Care Companion to the Journal of ClinicalPsychiatry vol 5 no 2 pp 70ndash73 2003

[6] N Chhabra M Aseri and D Padmanabhan ldquoA review of drugisomerism and its significancerdquo International Journal of Appliedand Basic Medical Research vol 3 no 1 pp 16ndash18 2013

[7] L Pu Ed 11rsquo-Binaphthyl-Based Chiral Materials Our JourneyWorld Scientific Hackensack NJ USA 2010

[8] B L Feringa andWR Browne EdsMolecular SwitchesWiley-VCH Weinheim Germany 2011

[9] J W Goodby P J Collings T Kato C Tschierske H Gleesonand P Raynes Eds Handbook of Liquid Crystals Wiley-VCHWeinheim Germany 2nd edition 2014

[10] N Katsonis E Lacaze and A Ferrarini ldquoControlling chiralitywith helix inversion in cholesteric liquid crystalsrdquo Journal ofMaterials Chemistry vol 22 no 15 pp 7088ndash7097 2012

[11] A Patti ldquoGreen approaches to asymmetric catalytic synthesisrdquoin Springer Briefs in Molecular Science Green Chemistry for Sus-tainability S K Sharma Ed Springer Dordrecht Netherlands2011

[12] V K Ahluwalia andM KidwaiNewTrends in Green ChemistryKluwer Academic New Delhi India 2004

[13] M Oestreich The Mizoroki-Heck Reaction Wiley ChichesterUK 2009

[14] DMcCartney andP J Guiry ldquoThe asymmetric heck and relatedreactionsrdquo Chemical Society Reviews vol 40 no 10 pp 5122ndash5150 2011

[15] C Wu and J Zhou ldquoAsymmetric intermolecular heck reactionof aryl halidesrdquo Journal of the American Chemical Society vol136 no 2 pp 650ndash652 2014

[16] O M Demchuk K Kapłon A Kącka and K M PietrusiewiczldquoThe utilization of chiral phosphorus ligands in atroposelectivecross-coupling reactionsrdquo Phosphorus Sulfur and Silicon andthe Related Elements vol 191 no 2 pp 180ndash200 2016

[17] H Yang X Yang and W Tang ldquoTransition-metal catalyzedasymmetric carbonndashcarbon cross-coupling with chiral ligandsrdquoTetrahedron vol 72 no 41 pp 6143ndash6174 2016

[18] A ChatterjeeHMallin J Klehr et al ldquoAn enantioselective arti-ficial Suzukiase based on the biotin-streptavidin technologyrdquoChemical Science vol 7 no 1 pp 673ndash677 2016

[19] Y Akai L Konnert T Yamamoto and M Suginome ldquoAsym-metric Suzuki-Miyaura cross-coupling of 1-bromo-2-naph-thoates using the helically chiral polymer ligand PQXphosrdquoChemical Communications vol 51 no 33 pp 7211ndash7214 2015

[20] S A Patil C-M Weng P-C Huang and F-E Hong ldquoCon-venient and efficient Suzuki-Miyaura cross-coupling reactionscatalyzed by palladium complexes containing NNO-tridentateligandsrdquo Tetrahedron vol 65 no 15 pp 2889ndash2897 2009

[21] A A C Braga N H Morgon G Ujaque A Lledos and FMaseras ldquoComputational study of the transmetalation processin the Suzuki-Miyaura cross-coupling of arylsrdquo Journal ofOrganometallic Chemistry vol 691 no 21 pp 4459ndash4466 2006

[22] L-P Chen and H-P Chen ldquoDFT Investigation on the mecha-nism of Pd(0) catalyzed sonogashira coupling reactionrdquo JiegouHuaxue vol 30 no 9 pp 1289ndash1297 2011

[23] W-J Sun W Chu L-J Yu and C-F Jiang ldquoLigand size effecton PdLn oxidative addition with aryl bromide A DFT studyrdquoChinese Journal of Chemical Physics vol 23 no 2 pp 175ndash1792010

[24] C Sicre AA C Braga FMaseras andMMCid ldquoMechanisticinsights into the transmetalation step of a Suzuki-Miyaurareaction of 2(4)-bromopyridines characterization of an inter-mediaterdquo Tetrahedron vol 64 no 30-31 pp 7437ndash7443 2008

[25] Q Liu Y Lan J Liu G Li Y-D Wu and A Lei ldquoRevealinga second transmetalation step in the Negishi coupling and itscompetition with reductive elimination improvement in theinterpretation of the mechanism of biaryl synthesesrdquo Journal ofthe American Chemical Society vol 131 no 29 pp 10201ndash102102009

[26] T Mondal S De B Maity and D Koley ldquoExploring theoxidative-addition pathways of phenyl chloride in the presenceof pd(II) abnormal n-heterocyclic carbene complexes A DFTstudyrdquo Chemistry vol 22 no 44 pp 15778ndash15790 2016

[27] H Xie T Fan Q Lei andW Fang ldquoNew progress in theoreticalstudies on palladium-catalyzed CminusC bond-forming reactionmechanismsrdquo Science China Chemistry vol 59 pp 1432ndash14472016

[28] S Raoufmoghaddam S Mannathan A J Minnaard J GDe Vries and J N H Reek ldquoPalladium(0)NHC-catalyzedreductive heck reaction of enones a detailedmechanistic studyrdquoChemistrymdashA European Journal vol 21 no 51 pp 18811ndash188202015

[29] S Sakaki Y-Y Ohnishi and H Sato ldquoTheoretical and compu-tational studies of organometallic reactions Successful or notrdquoChemical Record vol 10 no 1 pp 29ndash45 2010

[30] A Herrbach A Marinetti O Baudoin D Guenard and FGueritte ldquoAsymmetric synthesis of an axially chiral antimitoticbiaryl via an atropo-enantioselective Suzuki cross-couplingrdquoJournal of Organic Chemistry vol 68 no 12 pp 4897ndash49052003

[31] G Bringmann S Rudenauer T Bruhn L Benson and R BrunldquoTotal synthesis of the antimalarial naphthylisoquinoline alka-loid 5-epi-41015840-O-demethylancistrobertsonine C by asymmetricSuzuki cross-couplingrdquo Tetrahedron vol 64 no 23 pp 5563ndash5568 2008


[32] T Kamei A H Sato and T Iwasawa ldquoAsymmetric Suzuki-Miyaura cross-coupling of aryl chlorides with enhancement ofreaction time and catalyst turnoverrdquoTetrahedron Letters vol 52no 21 pp 2638ndash2641 2011

[33] C Amatore and F Pfluger ldquoMechanism of oxidative additionof palladium(0) with aromatic iodides in toluene monitored atultramicroelectrodesrdquo Organometallics vol 9 no 8 pp 2276ndash2282 1990

[34] J-F Fauvarque F Pfluger andMTroupel ldquoKinetics of oxidativeaddition of zerovalent palladium to aromatic iodidesrdquo Journal ofOrganometallic Chemistry vol 208 no 3 pp 419ndash427 1981

[35] J F Hartwig and F Paul ldquoOxidative addition of aryl bro-mide after dissociation of phosphine from a two-coordinatepalladium(0) complex bis(tri-o-tolylphosphine)palladium(0)rdquoJournal of the American Chemical Society vol 117 no 19 pp5373-5374 1995

[36] E Galardon S Ramdeehul J M Brown A Cowley K KHii and A Jutand ldquoProfound steric control of reactivity inaryl halide addition to bisphosphane palladium(0) complexesrdquoAngewandte ChemiemdashInternational Edition vol 41 no 10 pp1760ndash1763 2002

[37] N Miyaura and S L Buchwald ldquoCross-coupling reactions apractical guiderdquo inTopics in Current Chemistry p 248 SpringerBerlin Germany 2002

[38] LM Alcazar-Roman and J F Hartwig ldquoMechanistic studies onoxidative addition of aryl halides and triflates to Pd(BINAP)2and structural characterization of the product from aryl triflateaddition in the presence of aminerdquo Organometallics vol 21 no3 pp 491ndash502 2002

[39] S Shekhar P Ryberg and J F Hartwig ldquoOxidative addition ofphenyl bromide to Pd(BINAP) vs Pd(BINAP)(amine) Evidencefor addition to Pd(BINAP)rdquo Organic Letters vol 8 no 5 pp851ndash854 2006

[40] M Portnoy and D Milstein ldquoMechanism of aryl chlo-ride oxidative addition to chelated palladium(0) complexesrdquoOrganometallics vol 12 no 5 pp 1665ndash1673 1993

[41] S Vyskocil M Smrcina V Hanus M Polasek and P KocovskyldquoDerivatives of 2-amino-21015840-diphenylphosphino-111015840-binaphthyl(MAP) and their application in asymmetric palladium(0)-catalyzed allylic substitutionrdquo Journal of Organic Chemistry vol63 no 22 pp 7738ndash7748 1998

[42] S Vyskocil M Smrcina and P Kocovsky ldquoSynthesis of2-amino-2rsquo-diphenylphosphino-11rsquo-binaphthyl (MAP) and itsaccelerating effect on the Pd(0)-catalyzed N-arylationrdquo Tetra-hedron Letters vol 39 no 50 pp 9289ndash9292 1998

[43] T Hayashi ldquoChiral monodentate phosphine ligand MOP fortransition-metal-catalyzed asymmetric reactionsrdquo Accounts ofChemical Research vol 33 no 6 pp 354ndash362 2000

[44] O M Demchuk K Kielar and K M Pietrusiewicz ldquoRationaldesign of novel ligands for environmentally benign cross-coupling reactionsrdquo Pure and Applied Chemistry vol 83 no 3pp 633ndash644 2011

[45] U Christmann R Vilar A J P White and D J WilliamsldquoSynthesis of two novel dinuclear palladium(I) complexesand studies of their catalytic activity in amination reactionsrdquoChemical Communications vol 10 no 11 pp 1294-1295 2004

[46] T E Barder S D Walker J R Martinelli and S L BuchwaldldquoCatalysts for Suzuki-Miyaura coupling processes scope andstudies of the effect of ligand structurerdquo Journal of the AmericanChemical Society vol 127 no 13 pp 4685ndash4696 2005

[47] T Iwasawa T Komano A Tajima et al ldquoPhosphines hav-ing a 2345-tetraphenylphenyl moiety effective ligands in

palladium-catalyzed transformations of aryl chloridesrdquo Orga-nometallics vol 25 no 19 pp 4665ndash4669 2006

[48] Q Zhao C Li C H Senanayake and W Tang ldquoAn efficientmethod for sterically demanding Suzuki-Miyaura couplingreactionsrdquo ChemistrymdashA European Journal vol 19 no 7 pp2261ndash2265 2013

[49] P J Milner T J Maimone M Su J Chen P Muller andS L Buchwald ldquoInvestigating the dearomative rearrangementof biaryl phosphine-ligated Pd(II) complexesrdquo Journal of theAmerican Chemical Society vol 134 no 48 pp 19922ndash199342012

[50] M Su and S L Buchwald ldquoA bulky biaryl phosphine ligandallows for palladium-catalyzed amidation of five-memberedheterocycles as electrophilesrdquo Angewandte ChemiemdashInterna-tional Edition vol 51 no 19 pp 4710ndash4713 2012

[51] K Kapłon O M Demchuk and K M Pietrusiewicz ldquoTheDFT study on racemisation of atropisomeric biarylsrdquo CurrentChemistry Letters vol 4 no 4 pp 145ndash152 2015

[52] Y Zhao andDG Truhlar ldquoTheM06 suite of density functionalsfor main group thermochemistry thermochemical kineticsnoncovalent interactions excited states and transition ele-ments two new functionals and systematic testing of fourM06-class functionals and 12 other functionalsrdquo TheoreticalChemistry Accounts vol 120 no 1ndash3 pp 215ndash241 2008

[53] M J Frisch G W Trucks H B Schlegel et al Gaussian 09Revision A1 Gaussian Inc Wallingford Conn USA 2009

[54] Y Zhao and D G Truhlar ldquoDensity functionals with broadapplicability in chemistryrdquo Accounts of Chemical Research vol41 no 2 pp 157ndash167 2008

[55] R Jasinski ldquoSearching for zwitterionic intermediates in HeteroDiels-Alder reactions between methyl 120572p-dinitrocinnamateand vinyl-alkyl ethersrdquo Computational and Theoretical Chem-istry vol 1046 pp 93ndash98 2014

[56] O M Demchuk R Jasinski and K M Pietrusiewicz ldquoNewinsights into the mechanism of reduction of tertiary phosphineoxides by means of phenylsilanerdquo Heteroatom Chemistry vol26 no 6 pp 441ndash448 2015

[57] R Jasinski ldquoMolecular mechanism of thermal decompositionof fluoronitroazoxy compounds DFT computational studyrdquoJournal of Fluorine Chemistry vol 160 pp 29ndash33 2014

[58] R Jasinski E Dresler M Mikulska and D Polewski ldquo[3+2]Cycloadditions of 1-halo-1-nitroethenes with (Z)-C-(345-trimethoxyphenyl)-N-methyl-nitrone as regio- and stereocon-trolled source of novel bioactive compounds preliminary stud-iesrdquo Current Chemistry Letters vol 5 pp 123ndash128 2016

[59] V Barone M Cossi and J Tomasi ldquoGeometry optimization ofmolecular structures in solution by the polarizable continuummodelrdquo Journal of Computational Chemistry vol 19 no 4 pp404ndash417 1998

[60] V V Grushin and H Alper ldquoThe existence and stability ofmononuclear and binuclear organopalladium hydroxo com-plexes [(R3P)2Pd(R1015840)(OH)] and [(R3P)2Pd2(R1015840)2(120583-OH)2]rdquoOrganometallics vol 15 no 24 pp 5242ndash5245 1996

[61] V V Grushin andH Alper ldquoAlkali-induced disproportionationof palladium(II) tertiary phosphine complexes [L2PdCl2] toLO and palladium(0) Key intermediates in the biphasic car-bonylation ofArX catalyzed by [L2PdCl2]rdquoOrganometallics vol12 no 5 pp 1890ndash1901 1993

[62] J P Stambuli C D Incarvito M Buhl and J F HartwigldquoSynthesis structure theoretical studies and ligand exchangereactions of monomeric T-Shaped Arylpalladium(II) Halide


complexes with an additional weak agostic interactionrdquo Journalof the American Chemical Society vol 126 no 4 pp 1184ndash11942004

[63] B P Fors D A Watson M R Biscoe and S L BuchwaldldquoA highly active catalyst for Pd-catalyzed amination reactionscross-coupling reactions using aryl mesylates and the highlyselective monoarylation of primary amines using aryl chlo-ridesrdquo Journal of the American Chemical Society vol 130 no41 pp 13552ndash13554 2008

[64] T J Maimone P J Milner T Kinzel Y Zhang M K Takaseand S L Buchwald ldquoEvidence for in situ catalyst modificationduring the Pd-catalyzed conversion of aryl triflates to arylfluoridesrdquo Journal of the American Chemical Society vol 133 no45 pp 18106ndash18109 2011

[65] A A C Braga G Ujaque and F Maseras ldquoA DFT study of thefull catalytic cycle of the Suzuki-Miyaura cross-coupling on amodel systemrdquo Organometallics vol 25 no 15 pp 3647ndash36582006

[66] T Nishikata Y Yamamoto and N Miyaura ldquo14-Additionof arylboronic acids and arylsiloxanes to 120572120573-unsaturatedcarbonyl compounds via transmetalation to dicationic palla-dium(II) complexesrdquo Organometallics vol 23 no 18 pp 4317ndash4324 2004

Submit your manuscripts athttpswwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 201

International Journal ofInternational Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal ofInternational Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


Ar

X

ArAr X

Reductiveelimination

Transmetallation

Oxidativeaddition

n = 1 2

n

n

+H

X = Hal OT

Ar1

Ar1

Ar

[PdIILn ]

[PdIIL ]

Ar1-B(OH)3 Ar

1-B(OH)2⊖

B(OH)3X

[Pd0L ] [Pd0

L4]

L = R3P R3N C=C A

⊖

O⊖

minus(4 minus n)L

f

r

Scheme 1 Generally accepted mechanism of SM reaction

the same time the nature of chirality transfer still remainsunclear and only general intuitivemechanistic considerationshave been published to date [30]

In highly enantioselective SuzukindashMiyaura couplingspalladium complexes of significantly sterically hindered lig-ands are usually used [16 18] Accurate computer calcu-lations of such large complexes need an extremely largecomputational cost Additionally for palladium catalystsbased on regular bidentate ligands (eg BINAP (I) [31])and monodentate ligands (eg oligo-aryl phosphine (II) andoligo-aryl phosphonites (III) [32]) (Figure 1) several differentmodels of solvation and mono- and biscomplexation shouldbe evaluated [23 33ndash36] Obviously a discovery of subtleinteractions influencing the absolute configuration of theproduct formed in the reaction mediated by interconvertingcomplexes of large phosphorus ligands cannot be accuratebecause of many entropic issues that certainly take place butare difficult to handle In the case of less bulky and especiallybisphosphine chelating ligands different types of 14-electronPdL2 complexes have been postulated as active catalysts andcorresponding products of the oxidative addition reactionsto such complexes have been characterised [37ndash40]Thus wedecided to concentrate on highly efficient also in asymmetricSM reactions chiral ligands of the CP-type of complexationrepresented by KenPhos and similar ones (IV) [30 41 42]MeO-MOP (V) [43] and BisNap-Phos (VI) [44] (Figure 1)These ligands form well-defined bidentate mono-P-ligandedPd(0) species [45ndash48] with the structures formally corre-sponding to the 12-electron Pd-P(III) active catalysts of theSM reaction (Scheme 2 AC) The active catalyst is extremelyreactive and readily undergoes oxidative addition reactionwith aromatic halides to form intermediates with a well-defined structure I1 [49 50]

Even such simple complexes are spatially developed andcomplicated enough not to allow accurate computation oftheir fine properties and stereochemical behaviour if theentire structure is considered Nevertheless in the case ofcatalytic systems in which substrates and ligands do notbear bending function groups (whose interaction can con-trol the geometry of preordination intermediates) and thecatalyst is a complex of the CP-ligand the geometry of theintermediates is less sensitive to the substitution pattern andseveral coordinal simplifications can be applied Thus thegeometry of the palladium complexes will remain almost thesame if the cyclohexyl groups situated on the phosphorusatom are replaced with methyl groups Also the biarylcore of the ligand can be simplified to formally chiral 621015840-dimethylbiphenyl and eventually 2-bromotoluene and 2-tolylboronic acid can be selected as the simplest substrates ofthe enantioselective cross-coupling reaction (Scheme 3)Thissignificant simplification allows accurate DFT calculationsof the entire reactions leading to the chiral (but with lowracemisation energy) product [51]

With the objective of gaining insight into the originof stereoselectivity of the selected reacting system run inaqueous media we decided to perform DFT simulationsof possible reaction paths to confirm its actual molecularmechanismandfind conditions influencing the configurationof the chiral product formed

2 Results and Discussion

21 Computational Procedure The quantum-chemical cal-culations reported in this paper were performed on ldquoZeusrdquoand ldquoPrometheusrdquo supercomputers in the ldquoCyfronetrdquo com-putational centre in Cracow The M062x [52] functional


I

Me

Me

Me

Me

Me

OMe

Me

G

II

IIIO

OP

IV V

MeO O

VI

R = Ph Cy

PPh2

PPh2

PPh2

G = PPh2

G =

NMe2

PR2

PCy120784


Pd S


Pd Pd+S

minusS Ar-Hal

Pd Ar

Hal

AC I1

fast

PC

PR2PR2PR2PR2





Me

Br

Pd

Me

Me

Me

Me

Me

OH

OHOH

1

2 3

Me

Me

Pd

2

Me

Me

Pd

120784998400

PMe2 PMe2

PMe2

B⊖

-Brminus

-B(OH)3








P

Pd

2a

PMe

Me

Pd

F

F

F

F

F

F

F

FMe Me

MeMe

MeMe

120784a998400


Pd

2

Me

Me Me

Pd

+

MePMe2

PMe2

(a)

MeMe

MeMe+

PMe2

PMe2

(b)










Br

Pd 1

2

Me

Me

MeMe

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Pd

Br

Pd Br

Pd

Br

5a

5b

Pd Br

5c

5d

PMe2

PMe2

PMe2

PMe2PMe2


minus5

minus15

Reaction coordinate

minus10

minus25

minus20

minus35

minus30

5

2

1

5a

5b

5d

5c

Pd

MeMe

MeBr

PMe2

ΔG

(kca

lmol

)

Pd

Pd

Me

Me

MeMe

MeMe

Br

Br

PMe2

PMe2

Pd

PdMe

MeMe

Me

MeMe Br

Br

PMe2

PMe2

ΔGakt = 29 kcalmol


ΔGakt = 27 kcalmol


ΔGakt = 14 kcalmol


ΔGakt = 02 kcalmol








P Pd12 3

CyCy

MeO

MeO

Br

Pri

Pri

Pri


PPd

Bra

b

BO

OHOH

6Me

MeMe

Me

Me

Me

Me

BO

OHOH

6

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

H

7



ParameterP

Pd

123

BrAr

CyCy

5c VII VII1015840


∘] 10317 10608 10673AngleC3-Pd-P [

∘] 6473 8371 8115AnglePd-P-C1 [

∘] 11388 10635 10519








Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP


P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3



minus






minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


I

Me

Me

Me

Me

Me

OMe

Me

G

II

IIIO

OP

IV V

MeO O

VI

R = Ph Cy

PPh2

PPh2

PPh2

G = PPh2

G =

NMe2

PR2

PCy120784


Pd S


Pd Pd+S

minusS Ar-Hal

Pd Ar

Hal

AC I1

fast

PC

PR2PR2PR2PR2





Me

Br

Pd

Me

Me

Me

Me

Me

OH

OHOH

1

2 3

Me

Me

Pd

2

Me

Me

Pd

120784998400

PMe2 PMe2

PMe2

B⊖

-Brminus

-B(OH)3








P

Pd

2a

PMe

Me

Pd

F

F

F

F

F

F

F

FMe Me

MeMe

MeMe

120784a998400


Pd

2

Me

Me Me

Pd

+

MePMe2

PMe2

(a)

MeMe

MeMe+

PMe2

PMe2

(b)










Br

Pd 1

2

Me

Me

MeMe

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Pd

Br

Pd Br

Pd

Br

5a

5b

Pd Br

5c

5d

PMe2

PMe2

PMe2

PMe2PMe2


minus5

minus15

Reaction coordinate

minus10

minus25

minus20

minus35

minus30

5

2

1

5a

5b

5d

5c

Pd

MeMe

MeBr

PMe2

ΔG

(kca

lmol

)

Pd

Pd

Me

Me

MeMe

MeMe

Br

Br

PMe2

PMe2

Pd

PdMe

MeMe

Me

MeMe Br

Br

PMe2

PMe2

ΔGakt = 29 kcalmol


ΔGakt = 27 kcalmol


ΔGakt = 14 kcalmol


ΔGakt = 02 kcalmol








P Pd12 3

CyCy

MeO

MeO

Br

Pri

Pri

Pri


PPd

Bra

b

BO

OHOH

6Me

MeMe

Me

Me

Me

Me

BO

OHOH

6

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

H

7



ParameterP

Pd

123

BrAr

CyCy

5c VII VII1015840


∘] 10317 10608 10673AngleC3-Pd-P [

∘] 6473 8371 8115AnglePd-P-C1 [

∘] 11388 10635 10519








Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP


P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3



minus






minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Me

Br

Pd

Me

Me

Me

Me

Me

OH

OHOH

1

2 3

Me

Me

Pd

2

Me

Me

Pd

120784998400

PMe2 PMe2

PMe2

B⊖

-Brminus

-B(OH)3








P

Pd

2a

PMe

Me

Pd

F

F

F

F

F

F

F

FMe Me

MeMe

MeMe

120784a998400


Pd

2

Me

Me Me

Pd

+

MePMe2

PMe2

(a)

MeMe

MeMe+

PMe2

PMe2

(b)










Br

Pd 1

2

Me

Me

MeMe

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Pd

Br

Pd Br

Pd

Br

5a

5b

Pd Br

5c

5d

PMe2

PMe2

PMe2

PMe2PMe2


minus5

minus15

Reaction coordinate

minus10

minus25

minus20

minus35

minus30

5

2

1

5a

5b

5d

5c

Pd

MeMe

MeBr

PMe2

ΔG

(kca

lmol

)

Pd

Pd

Me

Me

MeMe

MeMe

Br

Br

PMe2

PMe2

Pd

PdMe

MeMe

Me

MeMe Br

Br

PMe2

PMe2

ΔGakt = 29 kcalmol


ΔGakt = 27 kcalmol


ΔGakt = 14 kcalmol


ΔGakt = 02 kcalmol








P Pd12 3

CyCy

MeO

MeO

Br

Pri

Pri

Pri


PPd

Bra

b

BO

OHOH

6Me

MeMe

Me

Me

Me

Me

BO

OHOH

6

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

H

7



ParameterP

Pd

123

BrAr

CyCy

5c VII VII1015840


∘] 10317 10608 10673AngleC3-Pd-P [

∘] 6473 8371 8115AnglePd-P-C1 [

∘] 11388 10635 10519








Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP


P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3



minus






minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


P

Pd

2a

PMe

Me

Pd

F

F

F

F

F

F

F

FMe Me

MeMe

MeMe

120784a998400


Pd

2

Me

Me Me

Pd

+

MePMe2

PMe2

(a)

MeMe

MeMe+

PMe2

PMe2

(b)










Br

Pd 1

2

Me

Me

MeMe

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Pd

Br

Pd Br

Pd

Br

5a

5b

Pd Br

5c

5d

PMe2

PMe2

PMe2

PMe2PMe2


minus5

minus15

Reaction coordinate

minus10

minus25

minus20

minus35

minus30

5

2

1

5a

5b

5d

5c

Pd

MeMe

MeBr

PMe2

ΔG

(kca

lmol

)

Pd

Pd

Me

Me

MeMe

MeMe

Br

Br

PMe2

PMe2

Pd

PdMe

MeMe

Me

MeMe Br

Br

PMe2

PMe2

ΔGakt = 29 kcalmol


ΔGakt = 27 kcalmol


ΔGakt = 14 kcalmol


ΔGakt = 02 kcalmol








P Pd12 3

CyCy

MeO

MeO

Br

Pri

Pri

Pri


PPd

Bra

b

BO

OHOH

6Me

MeMe

Me

Me

Me

Me

BO

OHOH

6

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

H

7



ParameterP

Pd

123

BrAr

CyCy

5c VII VII1015840


∘] 10317 10608 10673AngleC3-Pd-P [

∘] 6473 8371 8115AnglePd-P-C1 [

∘] 11388 10635 10519








Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP


P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3



minus






minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Br

Pd 1

2

Me

Me

MeMe

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Pd

Br

Pd Br

Pd

Br

5a

5b

Pd Br

5c

5d

PMe2

PMe2

PMe2

PMe2PMe2


minus5

minus15

Reaction coordinate

minus10

minus25

minus20

minus35

minus30

5

2

1

5a

5b

5d

5c

Pd

MeMe

MeBr

PMe2

ΔG

(kca

lmol

)

Pd

Pd

Me

Me

MeMe

MeMe

Br

Br

PMe2

PMe2

Pd

PdMe

MeMe

Me

MeMe Br

Br

PMe2

PMe2

ΔGakt = 29 kcalmol


ΔGakt = 27 kcalmol


ΔGakt = 14 kcalmol


ΔGakt = 02 kcalmol








P Pd12 3

CyCy

MeO

MeO

Br

Pri

Pri

Pri


PPd

Bra

b

BO

OHOH

6Me

MeMe

Me

Me

Me

Me

BO

OHOH

6

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

H

7



ParameterP

Pd

123

BrAr

CyCy

5c VII VII1015840


∘] 10317 10608 10673AngleC3-Pd-P [

∘] 6473 8371 8115AnglePd-P-C1 [

∘] 11388 10635 10519








Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP


P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3



minus






minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


P Pd12 3

CyCy

MeO

MeO

Br

Pri

Pri

Pri


PPd

Bra

b

BO

OHOH

6Me

MeMe

Me

Me

Me

Me

BO

OHOH

6

P

Me

Me

Me

Me

Me

PdO B

OH OHMe

H

7



ParameterP

Pd

123

BrAr

CyCy

5c VII VII1015840


∘] 10317 10608 10673AngleC3-Pd-P [

∘] 6473 8371 8115AnglePd-P-C1 [

∘] 11388 10635 10519








Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP


P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3



minus






minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Pd Br

TS1 TS2

PdBrP P

O B

TS3 TS4

PdP O

B

PdP


P

Me

Me

Me

Me

Me

PdO B

OH OHMe

Me

Me

MeMe

Me

Me Me

Me

Me

Me

Me

MeH

7

PPd

O B

OHOH

H

TS3

ne

PPd

8

-B(OH)3



minus






minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


minus5

minus15

Reaction coordinate

TS1

minus10

minus30

minus20

minus40

minus35

minus45

minus55

minus50

minus65

minus60

TS2 TS3

TS4

Pd

2

MeMe

Me

Br

Pd

Pd

Pd

Pd

P

P

OH OHOH

B

5c

Br

1

7

8

molecular complex

2

+

PMe2

Me

Me

Me

MeMe

MeMe

Me

Me

Me

MeMe

Me

MeMe

Me

MeMe

PMe2

Br

PMe2

5cAr-B(OH)3

minus

Ar-B(OH)3minus

PdMe

Me

MeMe

PMe2

Brminus B(OH)3

ΔG

(kca

lmol

)



3 Conclusions






Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




Acknowledgments


References
















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

a quantum-chemical dft approach to elucidation of the

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