145

Conferences / Symposia

[1] An oral presentation entitled “Fe(Cp)2PF6: An efficient catalyst for Mannich

reaction under solvent free condition” in the national conference on “Chemistry

for the Protection of Environment” held December on 18-19, 2009 at

Priyadarshini Institute of Engineering and Technology, Nagpur.

[2] A poster entitled “Titanium-Amino Alcohol Schiff Base Derived Complex Catalyzed

Asymmetric Oxidation of Prochiral Sulfides” was presented in the “National

Conference on Chirality 2011” held on December 2-3, 2011 at The Maharaja

Sayajirao University of Baroda, Vadodara.

[3] A poster titled as “Oxidative Kinetic Resolution of secondary alcohols using chiral

macrocyclic Mn(III) salen complexes” was presented in the National symposium

on “Catalysis for sustainable Development” on January 27-28, 2012 at M. S

university at Baroda.

[4] A poster entitled, “Highly enantioselective sulfide oxidation with chiral iron

complex using aqueous hydrogen peroxide as terminal oxidant” in 16th RSC-CRSI

National symposium held on February 6-9, 2014 at IITB, Mumbai.

Awards

[1] UGC- Junior Research Fellowship award from March 2009- March 2011.

[2] UGC- Senior Research Fellowship award from March 2011- March 2014.

Applied Catalysis A: General 467 (2013) 542– 551

Contents lists available at ScienceDirect

Applied Catalysis A: General

j ourna l h omepa ge: www.elsev ier .com/ locate /apcata

Macrocyclic Mn(III) salen complexes as recyclable catalystfor oxidative kinetic resolution of secondary alcohols

Prasanta Kumar Bera, Nabin Ch. Maity, Sayed H.R. Abdi ∗, Noor-ul H. Khan,Rukhsana I. Kureshy, Hari C. BajajDiscipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSMCRI), Council of Scientific & Industrial Research(CSIR), G. B. Marg, Bhavnagar 364 002, Gujarat, India

a r t i c l e i n f o

Article history:Received 22 May 2013Received in revised form 25 July 2013Accepted 26 July 2013

Keywords:Oxidative kinetic resolutionChiral macrocyclic Mn(III) salen complexesSecondary alcoholsDiacetoxyiodobenzeneN-bromosuccinimide

a b s t r a c t

New macrocyclic chiral Mn(III) salen complexes (C1–C4) were synthesized and were used as catalystsfor oxidative kinetic resolution (OKR) of secondary alcohols with diacetoxyiodobenzene (PhI(OAc)2) andN-bromosuccinimide (NBS), in biphasic dichloromethane: water solvent mixture. Good to excellent enan-tioselectivities were achieved with catalyst C2 for several secondary alcohols having different stericenvironment. In general with catalyst C2, NBS as a co-oxidant showed better enantioselectivity thanPhI(OAc)2 in OKR. The catalyst C2 was easily retrieved from the reaction mixture by the addition of hex-ane and recycled seven times both with NBS and PhI(OAc)2 as co-oxidants without losing its performance.Based on the experimental results a mechanism for OKR of racemic 1-phenylethanol has been proposedwhere (R,R)-Mn-salen preferably binds with (S)-1-phenylethanol to give (R)-1-phenylethanol in excessat the end of the reaction.

© 2013 Elsevier B.V. All rights reserved.

1. Introduction

Oxidative kinetic resolution (OKR) of racemic secondary alco-hols is one of the significant methods to get optically puresecondary alcohols having several applications viz., chiral auxil-iary and synthetic intermediates in pharmaceutical, agrochemicaland fine chemical industries [1]. Several chiral ligands with Pd[2], Ru [3], Ir [4], Co [5] and Fe [6] metal ions have been usedas catalyst for OKR in the past. But, chiral Mn(III) complexes [7],particularly Mn(III) salen type complexes [7a–7h] are of particu-lar interest due to their easy synthesis, mild reaction condition andvery short reaction time. Till date commercially available Jacobson’sMn(III) salen complex has shown highest activity and enantioselec-tivity in the OKR of racemic secondary alcohols by using oxidativemixtures such as KBr + PhIO and KBr + PhI(OAc)2. However, therecovery of the catalyst from the reaction mixture for further usewas hampered by its high solubility in all the commonly used sol-vents. Moreover, a fair amount of black particles was observed inthe post catalysis work-up process, possibly due to the oxidativedegradation of the catalyst. This resulted in poor recovery of thecatalyst even by silica gel chromatographic separation. In the oxida-tive environment the situation is further complicated as Mn(III)salen complex, if not properly designed, tend to form catalytically

∗ Corresponding author. Tel.: +91 0278 2567760; fax: +91 0278 2566970.E-mail addresses: shrabdi@csmcri.org, raziabdi56@gmail.com (S.H.R. Abdi).

inactive (and/or non-selective) dimeric and polymeric �-oxoMn(IV) species. Undoubtedly, catalyst recycle is an important issue,more so to offset the high cost of the catalyst for practical appli-cation. In this context, it is prudent to design a ligand/complexthat has built-in capability of (a) preventing di(poly)merisationof the catalyst by site isolation, (b) minimizing auto oxidationand (c) altering its solubility so that it is easily retrieved in post-catalytic work-up step. Some of these issues particularly catalystrecyclability in OKR of racemic alcohol was addressed earlier byincorporating sulfonato-Mn(III) salen complex on an organic resin[7i], but the catalyst showed only moderate enantioselectivityalthough recycled up to 4th cycle. Later on our group [7d,e] andXia et al. [7g] introduced dimeric and polymeric Mn(III) salen com-plexes as recyclable catalysts which were recycled up to 5th and 4thcycles respectively. Towards the goal of catalyst recyclability, theimmobilization of the chiral Mn(III) salen complexes into ionic liq-uid modified mesoporous silica [7j,k], could retain its activity andenantioselectivity only up to 4th cycle. Very recently Tan et al. [7f]have synthesized imidazolium based ionic liquid bridged Mn(III)salen complexes which were recycled successfully up to 5th cyclefor OKR of secondary alcohols with very good enantiomeric excessfor selected sterically similar substrates. We visualized the synthe-sis of Mn(III) salen system embedded in a macrocycle to addressabove mentioned issues. For this we have taken clue from the“Nature” for which T. J. Collins very aptly stated – ‘reaction sitesand transition states are crafted (in Nature) not only to acceler-ate desired reaction but also to exclude undesired process such as

0926-860X/$ – see front matter © 2013 Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.apcata.2013.07.055

Journal of Molecular Catalysis A: Chemical 361– 362 (2012) 36– 44

Contents lists available at SciVerse ScienceDirect

Journal of Molecular Catalysis A: Chemical

jou rn al h om epa ge: www.elsev ier .com/ locate /molcata

Titanium complexes of chiral amino alcohol derived Schiff bases as efficientcatalysts in asymmetric oxidation of prochiral sulfides with hydrogen peroxideas an oxidant

Prasanta Kumar Bera, Debashis Ghosh, Sayed Hasan Razi Abdi ∗, Noor-ul Hasan Khan,Rukhsana Ilays Kureshy, Hari Chandra BajajDiscipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSMCRI), Council of Scientific & Industrial Research (CSIR), G.B. Marg, Bhavnagar364 021, Gujarat, India

a r t i c l e i n f o

Article history:Received 28 December 2011Received in revised form 26 April 2012Accepted 27 April 2012Available online 8 May 2012

Keywords:Asymmetric oxidationSulfoxidationSchiff baseChiral titanium complexHydrogen peroxide

a b s t r a c t

An efficient asymmetric oxidation of prochiral sulfides catalyzed by a series of simple in situ generatedcomplexes based on chiral amino alcohol derived Schiff bases with Ti(Oi-Pr)4 was carried out in presenceof cheap and environmentally benign oxidant H2O2 at 0 ◦C. Prochiral sulfides were converted to respectivechiral sulfoxides efficiently (conversion, 93%; up to ee, 98%) with this system in 10 h at 0 ◦C. The presentstudy demonstrated a significant role of steric influence of the substituent attached on both aryl and alkylmoiety on the enantioselectivity. Kinetic studies of the catalytic reaction showed first order dependenceon substrate and catalyst whereas it is zero for the oxidant. Kinetic studies in combination with UV–vis.spectral studies were used to propose a catalytic cycle for the sulfoxidation reaction.

© 2012 Elsevier B.V. All rights reserved.

1. Introduction

Development of catalytic system for the synthesis of opti-cally pure sulfoxides is important in organic synthesis as thisclass of compounds are used as chiral auxiliary in asymmetricsynthesis [1–4], and as synthon in bioactive compounds, whichare increasingly finding application in pharmaceutical industry[5–8]. Asymmetric sulfoxidation of prochiral sulfides is exten-sively studied over the last two decades since its discovery byKagan (using Sharpless catalytic system) [9] and Modena [10].To introduce enantioselectivity, stoichiometric amount of chiraloxidants were either used directly [11–16] or in the presence ofTi(Oi-Pr)4 [17–19] with limited success. Several transition met-als such as vanadium [20–39] manganese [40–46] iron [47–50]and titanium [51–68] and few other metals, e.g., Zr, Pt, W, Mo,Ru and Al [69–74] with various types of chiral bidentate [52]tridentate [59] and tetradentate ligands [64] have also beenexplored to catalyze asymmetric sulfoxidation of prochiral sul-fides with various oxidants like TBHP/CHP [59,64], PhIO [45,46],oxaridine [16], (S)-norcamphor derived hydroperoxide [18] andH2O2 [29,31,35,47–50,59,62]. Besides these transition metals, fewenzyme catalyzed [75–80] sulfoxidation have also been reported,

∗ Corresponding author. Tel.: +91 0278 2567760; fax: +91 0278 2566970.E-mail address: shrabdi@csmcri.org (S.H.R. Abdi).

however, high chemo- and enantioselectivity remained elusive inmost cases particularly when titanium was used with H2O2 as anoxidant. Since, H2O2 is atom-efficient and environmentally benignit is most preferred oxidant for all practical purpose. Toward thisaim reports from Bolm group [47–59] are significant in terms ofgood product yield, selectivity and enantiomeric excess using H2O2as an oxidant and nontoxic iron complexes of amino alcohol derivedSchiff bases as catalysts. This system however is less active andenantioselective in the absence of an additive particularly Li/Nasalt of 4-methoxy benzoic acid. Alternatively, titanium complexesof amino alcohol derived Schiff bases can also be used as non-toxic catalyst with H2O2 as an oxidant but they were found to beless enantioselective in asymmetric sulfide oxidation reaction [65].Here we report titanium complexes of a series of amino alcoholderived Schiff bases as effective catalyst in asymmetric oxidationof various prochiral sulfides giving sulfoxides in moderate to excel-lent ee (30–98%) and selectivity (90–99%) with good conversion(58–93%), importantly, in the absence of an additive.

2. Experimental

2.1. General

All the sulfides were purchased from TCI and Acros.(1S,2R)-(+)-2-amino-1,2-diphenylethanol and (1R,2S)-(−)-2-amino-1,2-diphenylethanol, cumene hydroperoxide (CHP),

1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.http://dx.doi.org/10.1016/j.molcata.2012.04.014

Journal Name

Cite this: DOI: 10.1039/c0xx00000x

www.rsc.org/xxxxxx

Dynamic Article Links ►

ARTICLE TYPE

This journal is © The Royal Society of Chemistry [year] [journal], [year], [vol], 00–00 | 1

Manganese Complexes with Non-porphyrin N4 ligands as recyclable

catalyst for the Asymmetric Epoxidation of Olefins

Nabin Ch. Maity,a Prasanta Kumar Bera,

a Debashis Ghosh,

a,b Sayed H. R. Abdi,

*a,b Rukhsana I.

Kureshy,a,b Noor-ul H. Khan,

a,b Hari C. Bajaj,

a,b E. Suresh

b,c

Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX 5

DOI: 10.1039/b000000x

New chiral manganese complexes of N4 ligands derived from 2-acetylpyridine were prepared and used as

catalysts in the enantioselective epoxidation of olefins using H2O2 as an oxidant to give epoxides with

excellent conversions (up to 99%) and ee (up to 88%) within 1h at 0 oC. A detailed mechanistic study was

undertaken based on information as obtained by single crystal X-ray, optical rotation, UV-Vis, CD 10

spectra and kinetic studies revealed that reaction is first order with respect to concentration of catalyst and

oxidant and independent of substrate concentration. The complex (0.1 mol%) was successfully subjected

to recyclability experiments over 3 cycles in the epoxidation of styrene with H2O2 as an oxidant and

acetic acid as an additive at 0 oC with retention of performance.

Introduction 15

Catalytic asymmetric epoxidation is an important reaction1,2 as resulting enantiomerically pure epoxides are highly useful intermediates and building blocks.1-8 Host of works have been carried out on catalyst design with prime focus on achieving the targeted epoxide with high enantioselectivity and yield.1 Mn-20

salen catalysts,9-12 Shi’s ketone based system13-14 and Porphyrin-inspired catalysts15-16 are excellent methods to epoxidize a wide range of olefins with high enantioselectivity (>99% ee), yet substantial room for improvement remains in terms of catalyst loading, enantioselectivity and use of 25

ecofriendly oxidants with high atom efficiency.1 While numerous variants of salen ligands have been reported, only handful of bio-inspired non-heme N4 ligands3,4,7,8,17-25 with Mn have been studied. Nevertheless, these N4 ligands have shown very interesting results in asymmetric epoxidation of olefins 30

with ee up to 96% in selected substrates but mostly at -20 oC or below temperatures. Moreover, the synthetic protocols of these ligands are tedious, multi-step and often require expensive chiral starting materials. With this backdrop, we have come up to a simple methodology to synthesize chiral N4 ligands with 35

readily available chiral cyclohexanediamine and 2-acetylpyridine as starting materials in three convenient steps (Scheme 1) and used their manganese complexes in the asymmetric epoxidation of olefins with low catalyst loading (0.1 mol%) to get the product epoxide in ee 44-88% with high 40

turnover number (1000 which reached up to ~2500 after 3 catalytic cycles) in short reaction time (45-60 min) for the epoxidation of olefins, α,β-unsaturated ketone26 and chromenes with H2O2 as an oxidant and acetic acid as an additive at 0 oC.

H2N NH2N

O

+4 Å molecular sieves

K2CO3, dry toluene, N2N

N N

N

7 1 23

45

6

N

NH HN

N

7 1 23

45

6

NaBH4 MeOH, 6h

1R,2R-C3'''1S,2S-C3'''

7R,1R,2R,7'S-C3''7S,1S,2S,7'R-C3''

AcOH, NaBH4

H2CO, CH3CN

7'

7'

N

N N

N

7 1 23

45

6

7R,1R,2R,7'S-C3'7S,1S,2S,7'R-C3'

7'

N

N N

N

7 1 23

45

6

(7R,1R,2R,7'S)(-)-3

7'

MnMn(OTf)2

dry CH3CN, N2

(7S,1S,2S,7'R)(+)-3

N

NH NH

N

71 2

3

45

6

7'

Mn

TfO OH2

Mn(OTf)2dry CH3CN, N2

H2N NH2N

O

+ dry ethanol, N2

60 oCN

N N

N

71 2

3

45

6

7'

NaBH4 MeOH, 6h

N

NH HN

N

71 2

3

45

6

7'

1R,2R-C1'''

1R,2R-C1''

AcOH, NaBH4H2CO, CH3CN

N

N N

N

71 2

3

45

6

7'

1R,2R-C1'

N

N N

N

71 2

3

45

6

7'

1

Mn

TfO OH2

OTf

OTf

OTf

TfO OH2

Mn(OTf)2dry CH3CN, N2

(7R,1R,2R,7'S)-(+)-2

(7S,1S,2S,7'R)

-(-)-2

45

Scheme 1: Scheme for synthesis of the complexes.

Results and Discussion

The protocol used in the present study to synthesize bio-inspired novel N4 ligand is very simple and required no chromatographic purification. The starting materials 2-50

acetylpyridine, pyridine 2-carboxaldehyde and optically pure 1,2-diaminocyclohexane are inexpensive and readily available. These tetradentate ligands display C2-symmetry with two

Page 2 of 10Catalysis Science & Technology

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View Article OnlineDOI: 10.1039/C3CY00528C

CatalysisScience &Technology

PAPER

Cite this: Catal. Sci. Technol., 2014,

4, 563

Received 24th August 2013,Accepted 7th November 2013

DOI: 10.1039/c3cy00629h

www.rsc.org/catalysis

Asymmetric Friedel–Crafts addition of indoles toN-sulfonyl aldimines catalyzed by Cu(II) chiralamino alcohol based Schiff base complexes†

Prathibha Kumari,ab Prasanta Kumar Bera,a Noor-ul H. Khan,*ab

Rukhsana I. Kureshy,ab Sayed H. R. Abdiab and Hari C. Bajajab

Recyclable copper(II) chiral amino alcohol based Schiff base complexes smoothly catalysed the Friedel–Crafts

alkylation of indole with aryl aldimine in good yields (98%) and with enantioselectivities up to 97%. The effects

of ligand structure, solvent, metal source and temperature on the reaction were also studied. The catalytic

system worked very well several times retaining its performance. To understand the mechanism of the

catalytic Friedel–Crafts addition reaction, a kinetic investigation was carried out with different concentrations

of the catalyst Cu(II)–L2, indole and N-(3-nitrobenzylidene)-4-methylbenzene sulfonamide as a model

substrate. The Friedel–Crafts alkylation reaction of N-(3-nitrobenzylidene)-4-methylbenzene sulfonamide

was first order with respect to the concentration of the catalyst and the nucleophile but did not depend on

the initial concentration of the substrate (aryl aldimine). An appropriate mechanism of the Friedel–Crafts

alkylation reaction is proposed.

Introduction

The Friedel–Crafts alkylation of arenes is an importantcarbon–carbon bond forming reaction in organic chemistry.1

The asymmetric version of this reaction can provide a usefulstrategy for the synthesis of enantiomerically enriched alkylatedarene products, which are potential starting materials for manybiologically active compounds.2 Erker and Zeijden3 reportedin 1990 the first catalytic asymmetric Friedel–Crafts alkylationvia the addition of 1-naphthol to a pyruvic ester using a chiralzirconium complex. Since then various substrates viz., activecarbonyl compounds,4 epoxides,5 electron deficient/rich olefins6

and imines have been used for the Friedel–Crafts alkylationof indoles using various organocatalysts11–16 and metal-basedcatalysts particularly BINAP–Cu(I),7 bis(oxazoline)–Cu(II)8,9 anddinuclear zinc complexes10 giving products in high yield andwith excellent enantioselectivity. Although excellent results interms of yield and enantioselectivity have been achieved inFriedel–Crafts alkylations of indoles with imines, the synthetic

protocol for the reported catalysts are complex and multi-step.Moreover, these reports are silent on catalyst recyclability,which is an important aspect for the acceptability of thesecatalysts in industry for economic reasons. To address theseissues we used the chiral Schiff base ligands L1–L4 (Fig. 1) withCu(II) as catalysts for the Friedel–Crafts reaction of indoleswith various aryl aldimines giving good yields (98%) andenantioselectivities up to 97% of the 3-indolyl methanaminederivatives. The chiral Schiff base ligands L1–L4 were readilysynthesized from the reaction between the easily accessiblearomatic bis-aldehyde and different chiral amino alcohols and

aDiscipline of Inorganic Materials and Catalysis, Central Salt and Marine

Chemicals Research Institute (CSIR-CSMCRI), Council of Scientific & Industrial

Research (CSIR), G. B. Marg, Bhavnagar-364 002, Gujarat, India.

E-mail: khan251293@yahoo.in; Fax: +91 0278 2566970b Academy of Scientific and Innovative Research, Central Salt and Marine

Chemicals Research Institute (CSMCRI), Council of Scientific & Industrial

Research (CSIR), G. B. Marg, Bhavnagar-364 002, Gujarat, India,

Fax: +91 0278 2566970

† Electronic supplementary information (ESI) available See DOI: 10.1039/c3cy00629h Fig. 1 Structure of chiral Schiff bases L1–L4.

Catal. Sci. Technol., 2014, 4, 563–568 | 563This journal is © The Royal Society of Chemistry 2014

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DOI: 10.1002/cctc.201200700

Catalysis of Enantioselective Strecker Reaction in theSynthesis of d-Homophenylalanine Using Recyclable,Chiral, Macrocyclic MnIII–Salen ComplexesS. Saravanan, Noor-ul H. Khan,* Prasanta K. Bera, Rukhsana I. Kureshy, Sayed H. R. Abdi,Prathibha Kumari, and Hari C. Bajaj[a]

Introduction

The role of a-amino acids in asymmetric synthesis allows theiruse as catalysts in high-end applications in various fields, in-cluding the synthesis of pharmaceutical compounds.[1] Conse-quently, considerable effort has been devoted to the develop-ment of catalytic asymmetric approaches for the production ofoptically active a-amino acids. The asymmetric Strecker reac-tion is one of the most direct and viable methods for the syn-thesis of a-aminonitriles[2] (the precursor to a-amino acids) bythe addition of a cyanide source to imines in the presence ofchiral metal complexes, based on Ti, Al, Zr, V, Mn, and lantha-nides, with Schiff bases, BINOL, and other related ligands. [3]

Various cyanide sources are reported in the literature,[4]

among them TMSCN,[3f] and ethyl cyanoformate[3v, 5r] are consid-ered to be most safe, efficient, and commercially available. Inaddition to the use of chiral metal complexes as catalysts, sev-eral metal-free organocatalysts derived from chiral guanidines,ureas, thioureas, N-oxides, and ammonium salts have beenused effectively.[5] Among these catalysts, salen-based metal

complexes have emerged as an efficient protocol for the asym-metric Strecker reaction.[5a, b, f, 6]

Because salen ligands are easy to synthesize and amenableto fine-tuning in terms of electronic and steric features, theyhave attracted many researchers for use in various asymmetricorganic transformations.[6] Although chiral salen-based catalystsare easily accessible synthetically, they are still very expensive;hence their recyclability is of prime concern in offsetting thecatalyst cost. We have attempted to develop recyclable, chiral,dimeric and polymeric MnIII–salen[7] and, more recently, chiralMnIII–salen catalysts[7–9] for various organic transformations,such as the asymmetric cyanation of ketones,[8] epoxidation ofnon-functionalized alkenes,[9] oxidative kinetic resolution ofsecondary alcohols,[10] and enantioselective Strecker reaction ofimines.[3s]

Previously, we have reported the use of chiral, monomericand dimeric MnIII–salen complexes as catalysts for the enantio-selective Strecker reaction of N-benzyl benzylimines. Although,good conversions and excellent ee were obtained in selectedsubstrates with these systems„ the need for very low tempera-ture (�55 8C), high catalyst loading (15 mol %), and long reac-tion time (�28–36 h) led us to explore other variants of thesalen ligand to address these issues. Accordingly, we reporthere the use of chiral MnIII macrocylcic salen catalysts withtrigol, piperazine, and diethyl tartarate linkers at the salen lig-and’s 5,5’ position in the enantioselective Strecker reaction ofa broad range of, N-benzyl benzylimine and N-benzhydryliminesubstrates with TMSCN (trimethylsiyl cyanide) and EtOCOCN ascyanide sources in toluene.

A convenient approach to the asymmetric Strecker reactionwas established by synthesizing chiral, mono- and dinuclear,macrocyclic MnIII–salen complexes possessing achiral and chirallinkers (trigol, piperazine, and diethyl tartarate). This group ofmacrocyclic complexes has emerged as improved metal-basedcatalysts for the enantioselective Strecker reaction of aldimines,giving high enantioselectivity (up to 99 %) for a wide range ofsubstrates. The macrocylic complex 6 a with trigol linker worksvery well with TMSCN (trimethylsilyl cyanide) as a source of cy-anide, using 4-phenyl pyridine N-oxide (4-PPyNO) as a co-cata-lyst in toluene at �40 8C. However, the macrocyclic complex6 b with diethyl tartarate as a linker affected excellent chiral in-

duction for both aromatic and aliphatic imines with a safer cy-anide source (ethyl cyanoformate) in toluene at �20 8C in thepresence of N,N-diisopropylimine as a co-catalyst. Complexes6 a and 6 b used in the present study were recoverable and re-cyclable (five times) with retention of their performance atgram level. The kinetic study with complex 6 a for the enantio-selective Strecker reaction of N-benzyl benzylimine revealeda first-order dependence on catalyst, substrate, and TMSCNconcentration. This protocol with catalyst 6 b was further ex-tended for the synthesis of d-homophenyl alanine, an impor-tant analogue in factor Xa inhibitors.

[a] S. Saravanan, Dr. N. H. Khan, P. K. Bera, Dr. R. I. Kureshy, Dr. S. H. R. Abdi,P. Kumari, Dr. H. C. BajajDiscipline of Inorganic Materials and CatalysisCentral Salt and Marine Chemicals Research Institute (CSMCRI)Council of Scientific & Industrial Research (CSIR)G. B. Marg, Bhavnagar 364 021, Gujarat (India)Fax: (+ 91) 0278-2566970E-mail : khan251293@yahoo.in

Supporting information for this article is available on the WWW underhttp://dx.doi.org/10.1002/cctc.201200700.

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CHEMCATCHEMFULL PAPERS

Synthesis of enantiopure b-amino alcohols via AKR/ARO of epoxides usingrecyclable macrocyclic Cr(III) salen complexes

Rukhsana Ilays Kureshy *, K. Jeya Prathap, Manish Kumar, Prasanta Kumar Bera, Noor-ul Hasan Khan,Sayed Hasan Razi Abdi, Hari Chandra BajajDiscipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute (CSMCRI), Council of Scientific & Industrial Research (CSIR),G. B. Marg, Bhavnagar 364 021, Gujarat, India

a r t i c l e i n f o

Article history:Received 1 July 2011Received in revised form 24 August 2011Accepted 27 August 2011Available online 1 September 2011

Keywords:Aminolytic kinetic resolutionanti/syn-b-Amino alcoholsAsymmetric catalysisChiral macrocylic salenChromiumtrans/meso-Epoxides

a b s t r a c t

A series of chiral macrocyclic Cr(III) salen complexes 1e8 were synthesized and characterized. Thesecomplexes were found to be highly active, regio-, diastereo-, and enantioselective catalysts in aminolytickinetic resolution (AKR) of racemic trans-epoxides as well as asymmetric ring opening (ARO) of prochiralmeso-epoxides with various anilines as nucleophiles at room temperature in 18e24 h. Excellent yields(>99% with respect to the nucleophile) with high enantioselectivity (ee, >99%) of chiral anti-b-aminoalcohols was achieved with concomitant recovery of corresponding epoxides in high ee (up to >99%).The complex 1 also catalyzed the ARO of meso-epoxides to provide corresponding syn-b-amino alcoholsin high yield (99%) and ee (up to 91%). Due to built-in basic sites in the catalyst, no external base (as anadditive) was required to promote AKR and ARO reactions. The catalyst 1 was conveniently recycledseveral times with retention of its performance. The AKR of trans-stilbene oxide with aniline wassuccessfully demonstrated at relatively higher scale (10 mmol) using the catalyst 1.

� 2011 Published by Elsevier Ltd.

1. Introduction

Chiral b-amino alcohols are valuable intermediates for thepreparation of various biologically active compounds1 and chiralligands,2 hence their preparation has attracted attention of manyresearch groups worldover.3e9 Aminolytic kinetic resolution8,9

and asymmetric ring opening reactions4e7 of racemic and meso-epoxides are among the smartest strategies to prepare b-aminoalcohols in high optical purity because of the ready availability ofraw materials at a very economical prices. Jacobsen et al.10 andKatsuki et al.11 have demonstrated the amazing ability of chiralsalen ligands in preparing various metal complexes to catalyzenumerous asymmetric organic transformations. Consequently,Bartoli et al. revealed the use of chiral monomeric Co(III) andCr(III) salen complexes in catalyzing AKR of terminal and trans-aromatic epoxides8a,b to produce b-amino alcohols in high ee. Thesame paper also demonstrated asymmetric aminolysis of meso-stilbene oxide to get corresponding syn-b-amino alcohol in ex-cellent ee (90%) in the presence of monomeric Cr(III) salen(10 mol %) as a catalyst. However, this reaction needed Et3N as anadditive to promote Cr(III) salen catalyzed AKR of meso-stilbene

oxide in 40 h. Further, recent several reports have demonstrateda cooperative role of catalytic sites in bimetallic macrocyclic/linear complexes12,13 in various enantioselective reactions. Takinga clue from these findings, we have designed new recyclablechiral macrocyclic salen complexes 1e8 bearing two chiral salenunits linked through tertiary nitrogens (basic sites) in hope ofharnessing the benefits of multiple catalytic sites (metal centers)and built-in basic sites. This is also in line of our continued in-terest in developing recyclable enantioselective catalysts for theepoxide ring opening reactions.5d,6a,8c,d,14 The chiral macrocyclicCr(III) salen catalysts synthesized for the present study (partic-ularly the complex 1) have demonstrated excellent performancein asymmetric AKR of racemic trans-epoxides with different an-ilines to give anti-b-amino alcohols in quantitative yields withexcellent enantioselectivity(ee, >99%) and with concomitant re-covery of corresponding epoxides in excellent optical purity (eeup to >99%) in 18 h at room temperature. The complex 1 alsodisplayed its competence in catalyzing ARO of meso-epoxideswith aniline to produce corresponding syn-b-amino alcohols inquantitative yields and high ee (84e91%). Significantly, as visu-alized, this system does not require an addition of a base additiveto promote the reaction. Notwithstanding their excellent perfor-mance in AKR and ARO, the complex 1 has also shown very goodrecyclability.

* Corresponding author. Fax: þ91 0278 2566970; e-mail address: rukhsana93@yahoo.co.in (R.I. Kureshy).

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Tetrahedron

journal homepage: www.elsevier .com/locate/ tet

0040-4020/$ e see front matter � 2011 Published by Elsevier Ltd.doi:10.1016/j.tet.2011.08.077

Tetrahedron 67 (2011) 8300e8307

PAPER www.rsc.org/obc | Organic & Biomolecular Chemistry

Influence of chirality using Mn(III) salen complexes on DNA binding andantioxidant activity

Noor-ul H. Khan,*a Nirali Pandya,a Manoj Kumar,b Prasanta Kumar Bera,a Rukhsana I. Kureshy,a

Sayed H. R. Abdia and Hari C. Bajaja

Received 16th April 2010, Accepted 24th June 2010DOI: 10.1039/c0ob00010h

Chiral Mn(III) salen complexes S-1, R-1, S-2, R-2, S-3 and R-3 derived from the respective chiral salenligands, viz., (1S,2S)-N,N¢-bis-[3-tert-butyl-5-chloromethyl-salicylidine]-1,2-cyclohexanediamineS-1¢/(1R,2R)-N,N¢-bis-[3-tert-butyl-5-chloromethyl-salicylidine]-1,2-cyclohexanediamine R-1¢/(1S,2S)-N,N¢-bis-[3-tert-butyl-5-N,N¢N¢triethylaminomethyl-salicylidine]-1,2-cyclohexanediaminedichloride S-2¢/(1R,2R)-N,N¢-bis-[3-tert-butyl-5-N,N¢N¢triethylaminomethyl-salicylidine]-1,2-cyclohexanediamine dichloride R-2¢/(1S,2S)-N,N¢-bis-[3,5-di-tert-butylsalicylidene]-1,2-cyclohexanediamine S-3¢ and (1R,2R)-N,N¢-bis-[3,5-di-tert-butyl-salicylidene]-1,2-cyclohexanediamineR-3¢, were synthesized. Characterization of the complexes was done by microanalysis, IR, LC-MS,UV-vis. and circular dichroism (CD) spectroscopy. Binding of these complexes with calf thymus DNA(CT-DNA) was studied by absorption spectroscopy, competitive binding study, viscosity measurements,circular dichroism measurements, thermal denaturation study and observation of their differentantioxidant activities. Among all the complexes used, the best result in terms of binding constant(intercalative) (130.4 ¥ 104) was achieved with the complex S-1 by spectroscopic titration. The complexS-1 showed strong antioxidant activity as well.

Introduction

Chirality plays a significant role in medicinal chemistry becauseonly one enantiomer of a drug molecule is likely to show desirabletherapeutic effects while other enantiomer can have a different oradverse biological response. A classical example of this behaviorwas noticed in the use of thalidomide—a drug that was prescribedfor morning sickness in pregnant women, where the R enantiomershowed drug action whereas S enantiomer caused birth defects.1

Recently, the interaction of transition metal complexes with DNAevoked great interest, due to their importance in designing of newand promising drugs, probes for nucleic acids,2–4 DNA-dependentelectron transfer reactions, DNA footprinting, sequence-specificcleaving agents and antitumor drugs.5–9 As DNA is chiral, itsinteraction with a molecule having a chiral center(s) is expectedto be influenced by diastereomeric ion-pair formation betweenthe two. Thus, different enantiomers of chiral metal complexesare expected to show different metallo-intercalation capacitywith essentially chiral DNA and protein molecules.10–16 As aconsequence of this interaction, different enantiomers of a metalcomplex may have variable effects on various biological reactions,especially those involving free-radicals like hydrogen peroxidedecomposition, superoxide anion (O2

-) dismutase, catalase, wateroxidation and ribonuclease reduction. These reactions are crucial

aDiscipline of Inorganic Materials and Catalysis, Central Salt and MarineChemicals Research Institute (CSMCRI), Council of Scientific & IndustrialResearch (CSIR), G. B. Marg, Bhavnagar-364 021, Gujarat, India.E-mail: khan251293@yahoo.in; Fax: +91-0278-2566970; Tel: +91-02782567760bMarine Biology and Ecology Discipline, Central Salt and Marine ChemicalsResearch Institute (CSMCRI), Council of Scientific & Industrial Research(CSIR), G. B. Marg, Bhavnagar-364 021, Gujarat, India; Fax: +91-0278-2566970; Tel: +91-0278 2567760

for scavenging superoxide and hydroxyl radicals, which are largelyresponsible for DNA mutation and membrane protein damagethat can lead to diseases like cancer, liver malfunction andcardiovascular problems.17–19 Among various transition metalcomplexes, Mn(II)20–22 and Mn(III) salen complexes23 have shownpromising results for the DNA binding and cleavage activity.Gravert and Griffin, in their exhaustive study on Mn(III) salencomplexes, have demonstrated that the presence of substituentshaving different steric and electronic features on the salen moietyhas a significant impact on their DNA binding/cleavage activity.They have also shown that in the case of chiral complexes(having no substituents on the salen moiety), different enantiomershave different DNA cleaving activity, the R enantiomer beingmore potent.24 Recently, Peng et al. reported chiral Mn(III) salencomplexes with a naphthaldehyde moiety for their potentialDNA binding and cleavage activities.20 However, in this studythe difference in DNA binding/cleavage activity between the twoenantiomers was found to be less pronounced. These results clearlydemonstrated that the DNA binding and cleavage activity ofthe Mn(III) salen complexes is strongly substituent dependent.However, Melvo et al. elegantly demonstrated the superoxidescavenging antioxidant activity of Mn salen complexes utilizingachiral ligands by xanthine–xanthine oxidase assay.25 Ironically,the role of chirality on superoxide and hydrogen peroxide radicalscavenging activities is conspicuously absent.

In view of the above and our ongoing interest in the synthesisof various chiral transition metal complexes as catalysts in variousorganic transformations26–29 and DNA binding and cleavagestudies,11 here, we are reporting the synthesis of chiral Mn(III)salen complexes, viz. S-1, R-1, S-2, R-2, S-3 and R-3, havingdifferent substituents such as chloromethyl, triethylaminomethyland tert-butyl at the 5,5¢-position of salen and examined their

This journal is © The Royal Society of Chemistry 2010 Org. Biomol. Chem., 2010, 8, 4297–4307 | 4297

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N,N-Dimethylpyridin-4-Amine Mediated Protocolfor Cyanoethoxycarbonylation of AldehydesUnder Solvent-Free Conditions

Noor-ul H. Khan • Santosh Agrawal •

Rukhsana I. Kureshy • Prasanta K. Bera •

Sayed H. R. Abdi • Hari C. Bajaj

Received: 2 February 2010 / Accepted: 19 April 2010 / Published online: 8 May 2010

� Springer Science+Business Media, LLC 2010

Abstract N,N-Dimethylpyridin-4-amine (DAMP) (10 mol%)

was successfully employed as catalyst for cyanoethoxy-

carbonylation of aromatic and aliphatic aldehydes at room

temperature under solvent free condition to give corre-

sponding ethylcyanocarbonates in excellent isolated yield

(up to 95%) in 15–90 min. Simple experimental conditions

and product isolation procedure has made this protocol

quite attractive for the synthesis of ethylcyanocarbonates in

an environment-friendly manner.

Keywords N,N-dimethylpyridin-4-amine �Cyanoethoxycarbonylation � Aldehydes � Solvent-free �Ethylcyanoformate

1 Introduction

Cyanohydrins are valuable intermediates for the synthesis

of range of compounds viz., a-amino acids, a-hydroxy

acids, b-amino alcohols, vicinal diols and a-hydroxy

ketones [1–5] which are important building blocks for

numerous pharmaceuticals, agrochemicals and insecti-

cides [6–13]. Cyanohydrins are conventionally synthe-

sized by the cyanation of carbonyl compounds using

KCN, NaCN, trimethylsilyl cyanide (TMSCN) and HCN

as sources of cyanide in the presence of various Lewis

acid/base catalysts [14–30]. Kobayashi et al. for the first

time have reported the use of triethylamine as an efficient

catalyst for the cyanosilylation of aldehydes to give

cyanosilylether in excellent yields [31]. However, this

protocol has used toxic TMSCN as a cyanide source and

environmentally hazardous dichloromethane as a solvent

at 0 �C. Therefore, in recent days, acylcyanides and

alkylcyanoformates are more preferred sources of cyanide

as they are safer, effective and easily available [32–37].

These cyanide sources however, required the use of a

base as catalyst to promote cyanation reaction [38–50]. In

this direction, Poirier and co-workers [51, 52] effectively

utilized various tertiary amines as catalysts for the

methoxycarbonylation of aldehydes whereas Deng and

co-workers [53, 54] have used a chiral base for the

cyanocarbonylation of ketones. On the other hand Oriyama

et al. [55] have reported the addition of acylcyanide to

aldehydes in the absence of a catalyst but used DMSO as

a solvent. All the above mentioned reactions were

invariably carried out in the presence of a solvent (often

toxic or hazardous) and required longer reaction time.

Therefore, a solvent-free protocol is preferred for the

practical applications. Recently Tian and co-workers have

reported the solvent-free cyanocarbonylation of aldehydes

using ethylcyanoformate as a source of cyanide in the

presence of 1-methoxy-2-methyl-1-(trimethylsiloxy)pro-

pene as a catalyst (5–25 mol%) to afford the desired

ethylcyanocarbonates in excellent yields in time ranging

from 9 h to 72 h [42]. Nevertheless, 1-methoxy-2-methyl-

1-(trimethylsiloxy)propene is highly volatile, moisture

sensitive and hazardous. Earlier, we have reported sol-

vent-free and environmentally benign synthetic protocols

for the synthesis of cyanosilylethers [56], aminonitriles

[57] and b-amino ketone (Mannich reaction) [58]. In this

context and our ongoing interest in cyanation of alde-

hydes [59–64], the present study describes the addition of

N. H. Khan (&) � S. Agrawal � R. I. Kureshy �P. K. Bera � S. H. R. Abdi � H. C. Bajaj

Discipline of Inorganic Materials and Catalysis, Central Salt

and Marine Chemicals Research Institute (CSMCRI), Council

of Scientific & Industrial Research (CSIR), G. B. Marg,

Bhavnagar 364 002, Gujarat, India

e-mail: khan251293@yahoo.in

123

Catal Lett (2010) 137:255–260

DOI 10.1007/s10562-010-0355-7