new catalyst in asymetric

7/17/2019 New Catalyst in Asymetric

http://slidepdf.com/reader/full/new-catalyst-in-asymetric 1/7

Stereoselective Alkylations

New Catalytic Approaches in the StereoselectiveFriedel–Crafts Alkylation Reaction**

Marco Bandini,* Alfonso Melloni, and Achille Umani-Ronchi*

Keywords:

alkylation · aromatic substitution · asymmetric

catalysis · Lewis acids · synthesis design

1. Introduction

The Friedel–Crafts (F–C) reaction is one of the oldest

organic transformations to employ Lewis acids as promoters,and since the pioneering study by Charles Friedel and

James M. Crafts[1] it has been one of the most powerful CC

bond-forming processes in organic synthesis.[2] The original

procedure (for which stoichiometric amounts of a Lewis acid

were required) has subsequently been replaced by milder and

more environmentally friendly conditions.[3] The ever-increas-

ing number of catalytic procedures reported in the literature

over the past decade for the catalytic alkylation and acylation

of aromatic and heteroaromatic compounds is striking

(Figure 1).[4]

In the mid-1980s the first examples of the asymmetric

addition of aromatic CH bonds to carbonyl compounds

appeared in the literature.[5]

Since then the synthetic rele-vance of the formation of benzylic carbon stereocenters

prompted several groups to develop

new stereoselective and catalytic strat-

egies.[6] Herein, a brief overview of the

most recent asymmetric protocols of

the metal- and organocatalyzed elec-

trophilic alkylation of aromatic com-

pounds is presented. We found it

convenient to gather the F–C alkyla-

tions into three sections: ring-opening reactions of epoxides

by aromatic compounds (Scheme 1a), enantioselective 1,2-

A fter more than 125 years, the Friedel–Crafts alkylation is still one of

the most studied and most utilized reactions in organic synthesis. What

is the secret of this astonishing success? Perhaps the great versatility in

scope and applicability continues to justify its crucial role in the

synthesis of more and more complex molecules. However, it has taken

more than a century for asymmetric catalytic versions of this reactionto be developed and subsequently extended to a range of aromatic

compounds and alkylating agents. Herein we review recent develop-

ments in the design and use of catalytic and stereoselective strategies

for the alkylation of aromatic systems and synthesis of a wide range of

polyfunctionalized enantiomerically enriched compounds.

Figure 1. The increasing number of catalytic Friedel–Crafts procedurespublished from 1991 to date.

Scheme 1. Possible approaches in the asymmetric Friedel–Craftsalkylation of aromatic compounds.

[*] Dr. M. Bandini, A. Melloni, Prof. Dr. A. Umani-RonchiDipartimento di Chimica “G. Ciamician”, Universit di BolognaVia Selmi, 2, 40126 Bologna (Italy)Fax: (

39)051-209-9456E-mail: [email protected]

[email protected]

[**] We thank “Progetti FIRB”, Consorzio C.I.N.M.P.I.S. (Bari),M.U.R.S.T. (Rome) “Progetto Stereoselezione in Chimica Organica.Metodologie ed Applicazioni”, and the University of Bologna (fundsfor selected research topics) for the financial support of thisresearch.

M. Bandini, A. Umani-Ronchi and A. MelloniMinireviews

550 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/anie.200301679 Angew. Chem. Int. Ed. 2004, 43, 550–556



additions of aromatic systems to carbonyl groups (Sche-

me 1b), and 1,4-conjugate additions of aromatic systems to

a,b-unsaturated carbonyl compounds (Scheme 1c).

2. Catalytic Stereocontrolled Ring-Opening of Epoxides by Aromatic Compounds

The ring-opening of epoxides by aromatic compounds in

the presence of Lewis acids, bases, and solid acids is widely

recognized as an effective step in the synthesis of polyfunc-

tionalized compounds.[7] Moreover, the ready availability of

enantioenriched cis and trans epoxides by means of various

stereoselective epoxidations makes this approach an attrac-

tive candidate for use as a tool in the synthesis of optically

active aromatic compounds. The main drawbacks encoun-

tered in this strategy are the occurrence of polyalkylation and

the frequent absence of regioselectivity. Only a few examples

involving enantiomerically enriched epoxides have been

described. In particular, Kotsuki et al. reported the regio-

and stereoselective alkylation of indole (2) with (R)-(

)-styrene oxide (1) promoted by high pressure or catalyzed by

silica gel (Scheme 2).[8] Although both approaches guaran-

teed satisfactory yields of 3, partial racemization of the

enantiomerically pure starting epoxide was observed (high

pressure: 92% ee, SiO2 : 88% ee).

The use of Lewis acids represents a valuable way to

promote and control the reactivity of oxiranes toward

nucleophiles. Furthermore, the electronic features of the

Lewis acid must be considered carefully to prevent the

formation of carbocation intermediates. In this context, the

mild Lewis acidity of indium(iii) salts and their relatively low

oxophilicity[9] make them suitable candidates for the promo-

tion of stereoselective alkylations of aromatic compounds by

the ring-opening of enantiomerically pure epoxides.

Our research group reported a highly stereoselective

alkylation of functionalized indoles with enantiomerically

pure aryl epoxides in the presence of anhydrous InBr3

(1 mol%).[10] The reaction, which proceeds exclusively

through a regio- and stereoselective SN

2-type pathway at

the benzylic position of the epoxide, allows a number of b-3-

indolyl alcohols 3 to be isolated in high yields and with

99 % ee (Scheme 3).

As a natural extension of the ring-opening of enantiomeri-

cally pure epoxides, we recently developed the first catalytic

asymmetric resolution of racemic internal aromatic oxiranes

through a carbon–carbon bond-forming reaction. It was found

that 2-methylindole reacts smoothly and regioselectively with

( )-styrene oxide (1) in the presence of a catalytic amount

(5 mol%) of the commercially available [Cr(salen)Cl] com-

plex 4 a (salen=N ,N ’-bis(3,5-di-tert -butylsalicylidene)-1,2-cy-

clohexanediamine) to afford both the unreacted styrene oxide

and the indolyl derivative 5 with moderate enantiomericexcess (55 and 56% ee, respectively, Scheme 4a).[11] By care-

ful tuning of the conversion of the kinetically controlled step,

the protocol allowed functionalized internal cis and trans

epoxides to be prepared in enantiomerically pure form (up to

99 % ee) and in moderate yields (Scheme 4 b). Moreover, the

[Cr(salen)Cl] 4 a was also found able to promote the

desymmetrization of meso stilbene oxide in the presence of

variously substituted indoles. The desired b-indolyl alcohols 5’

were isolated in excellent chemical yields and optical purities

(up to 98% yield, up to 98% ee, Scheme 5).

Marco Bandini was born in Faenza (Italy)

in 1973. He received his BSc degree(Laurea) in 1997 from the University of Bologna. In 1999 he spent a period in theresearch group of Prof. M. R. Gagn atNorth Carolina University, Chapel Hill. In2000 he received his PhD under the supervi-sion of Prof. Umani-Ronchi and was ap-pointed assistant professor at the Universityof Bologna. He was the recipient of theG.I.C.O. Junior Award of the Italian Chemi-cal Society in 2002. His current scientific in-terests are focused on asymmetric synthesismediated by homogeneous organometallic catalysts.

Alfonso Melloni, born in Padova (Italy) in

1973, received his BSc in chemistry fromthe University of Bologna in 1999. In 2000 he joined Prof. P. Bravo (Politecnico of Mi-lan), working on the total synthesis of fluori-nated pheromones. He is currently a PhDstudent in the research group of Prof. A. Umani-Ronchi. His research is focused onthe synthesis of optically active compoundsby employing chiral organometallic cata-lysts.

Scheme 2. High-pressure and silica-gel-catalyzed stereoselective ring-opening of (R)-(

)-styrene oxide.

Scheme 3. Regio- and stereoselective ring-opening of optically activeepoxides catalyzed by InBr3.

Friedel–Crafts Alkylations Angewandte

Chemie

551 Angew. Chem. Int. Ed. 2004, 43, 550 –556 www.angewandte.org 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

http://www.angewandte.org/




3. Catalytic Asymmetric Addition of Aromatic Compounds to C =O and C =NR Groups

The addition of electron-rich aromatic compounds to

aldehydes, ketones, and imines leads to the formation of

versatile functionalized compounds.[12] However, because of

the intrinsic instability of many aminomethyl and hydrox-

ymethyl aromatic systems, polysubstitution reactions to give

bisaryl compounds of the type 6 are commonly encountered

both under homogeneous and heterogeneous catalysis

(Scheme 6).[13] After the first catalytic asymmetric addition

of 1-naphthol (7) to pyruvic esters 8 mediated by the chiralzirconocene complex 9 (Scheme 7),[5b] a considerable break-

through in this area was made independently by Johannsen[14a]

and Mikami and co-workers.[14b] They described the synthesis

of heteroaromatic N -tosyl-a-amino acids catalyzed by tol-

binap/CuPF6 (the Lectka catalyst (10), Scheme 8) and the

preparation of organofluoro compounds by the addition of

electron-rich arenes to fluoral (11) in the presence of a chiral

substituted binol–titanium complex 12 (Scheme 9), respec-

Achille Umani-Ronchi graduated in

chemistry in 1960 from the University of Rome. He was an assistant at the Politecni-co of Milan (Italy) from 1961 to 1969, thenan assistant professor at the University of Bari. He spent one year (1964–65) as apostdoctoral fellow at the ETH in Zrich(Prof. D. Arigoni) and six months as a post-doctoral fellow at the University of Cam-bridge (Prof. J. Lewis). Since 1980 he hasbeen a full professor of organic chemistry atthe University of Bologna. In 2002 he re-ceived the Award of the Italian Chemical Society for his contributions to organic syn-thesis.

Scheme 4. Asymmetric kinetic resolution of cis and trans epoxidescatalyzed by [Cr(salen)X] complexes. TBDMS= tert-butyldimethylsilyl,TBME= tert-butyl methyl ether.

Scheme 5. Enantioselective desymmetrization of meso stilbene oxidecatalyzed by [Cr(salen)X] complexes.

Scheme 6. Bisindolyl compounds 6 as side products in Lewis acid(LA) mediated additions of indoles to carbonyl compounds.

Scheme 7. The use of a chiral zirconocene complex 9 as the catalystfor the addition of 1-hydroxynaphthalene (7) to the pyruvic esters 8.

Scheme 8. Enantioselective Friedel–Crafts alkylation of indoles cata-lyzed by the tol-binap–CuI complex 10. Ts=p-toluenesulfonyl, tol-bi-nap=bis[2,2’-(di-p-tolylphosphanyl)-1,1’-naphthyl].

AngewandteChemie M. Bandini, A. Umani-Ronchi and A. Melloni

552 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.angewandte.org Angew. Chem. Int. Ed. 2004, 43, 550–556





tively. In the latter case, a notable improvement in the

catalytic effectiveness was observed when biphenols were

added as activators (asymmetric activation) to the chiral

titanium-based Lewis acid.[15]

The range of accessible enantiomerically enriched a-

heteroarene a-amino acids, starting from a variety of substituted benzenes and furans, was improved remarkably

by utilizing the catalytic system 10 and a-imine esters 14 as

electrophiles.[16] In this study, several N-protecting groups

were tested, and the highest chemical yields and ee values

were observed when a readily removable N -carbamate group

was used (Scheme 10).

The synthetic versatility of the catalytic F–C alkylation

was further emphasized by Jørgensen and co-workers, who

were able to obtain aromatic mandelic esters 18[17a] and

heteroaromatic hydroxytrifluoromethyl esters 20[17b] by asym-

metric F–C reactions of aromatic compounds to ethyl

glyoxylate (16, Scheme 11a) and ethyl trifluoropyruvate

(19 a, Scheme 11b), respectively. The cationic t Bu-box–cop-

per(ii) triflate complex 17 (box=bisoxazoline) and chelating

substrates were used in these catalytic approaches to give highstereoselectivity. Under these conditions aromatic amines,

anisoles, and heteroaromatic compounds were all found to

undergo highly enantioselective F–C reactions, thus showing

the wide applicability of the catalytic system. However, less-

reactive substituted furans required a higher catalyst loading

(40 mol %) for satisfactory chemical yields to be observed.[18]

Corma et al. recently studied the first example of hetero-

geneous catalytic asymmetric F–C alkylation, in the reaction

of 1,3-dimethoxybenzene with methyl 3,3,3-trifluoropyruvate

(19 b) in the presence of a chiral Ph-box–copper(ii) complex

covalently anchored to silica or mesoporous MCM-41 (21,

Scheme 12).[19] The use of supported catalysts furnished the

same levels of stereoselectivity (82–92% ee, 72–77% con-

version) as observed in the homogeneous process

(86% ee),[17a] and the heterogeneous catalysts could be

recovered easily by filtration. The reusability of the chiral

catalyst 21–MCM-41 was also investigated, and the second

catalytic reaction afforded the same level of enantioselectivity(84% ee) and only a slight decrease in conversion (73%).

4. Catalytic Asymmetric Michael-Type Addition of Aromatic Compounds to a , b -Unsaturated Carbonyl Compounds

a,b-Unsaturated carbonyl compounds are suitable sub-

strates for F–C alkylations, and in fact numerous acid-

catalyzed Michael-type additions of aromatic compounds

have been described.[20] Nevertheless, stereoselective variants

have been less explored. The first example of highly

Scheme 9. Use of a binol–titanium complex 12 as the catalyst for theasymmetric addition of electron-rich arenes to fluoral (11).binol=1,1’-bis(2-naphthol).

Scheme 10. Enantioselective addition of electron-rich aromaticcompounds to imines catalyzed by 10.

Scheme 11. Stereoselective syntheses of substituted mandelic estersand heteroaromatic trifluoromethyl-substituted esters through F–Calkylations catalyzed by box–CuII complexes.

Scheme 12. Chiral copper catalyst anchored to solid supports (silica,MCM-41) as a mediator of the asymmetric alkylation of 1,3-dimethoxy-benzene. conv.=conversion.


Chemie






enantioselective catalytic 1,4-addition of electron-rich aro-

matic compounds to b,g-unsaturated-a-keto esters 22, in the

presence of the chiral box-copper(ii) complex 17, was

described by Jørgensen et al. (Scheme 13).[21] Later, Zhou

and Tang demonstrated the effectiveness of the pseudo-C 3-

symmetric trisoxazoline 25 complexed with Cu(ClO4)2·6 H2Oin promoting (both under anhydrous and non-anhydrous

conditions) the enantioselective addition of indole to aryli-

dene malonates 24 (R=Ar) at 20

C (Scheme 14).[22] The

data collected by the authors show that the presence of an

aromatic group bonded to the malonate CC double bond is

crucial for high enantioselectivity to be observed. When the

F–C reaction was carried out with an alkylidene malonate ( 24,

R=Me), the enantioselectivity dropped to 60% ee for the

product 26b. Comparison of the results obtained in the

analogous reaction by Jørgensen and co-workers with the

classic bidentate C 2-symmetric t Bu-box ligand (maximum

ee value: 69%)[23] shows the influence of the sidearm present

in the tridentate ligand 25.The use of chelating substrates in combination with chiral

cationic Lewis acids is a well-known strategy to ensure high

levels of stereoselectivity. However, it also represents a

significant restriction in applicability. A Michael-type reac-

tion between aromatic compounds and nonchelating a,b-

unsaturated carbonyl compounds was first reported by the

research group of MacMillan,[24] and more recently by our

research group.[25] MacMillan and co-workers elegantly

designed and employed the chiral tailored benzyl imidazo-

lidinone·HX salts 27a,b derived from (l)-phenylalanine as

organic catalysts for the 1,4-addition of pyrroles, indoles, and

aniline derivatives to a,b-unsaturated aldehydes (Scheme 15).

The LUMO-lowering activation of aldehydes by reversible

formation of chiral intermediate iminium salts 28

(Scheme 16) is responsible for the modulation of both

reactivity and stereoselectivity in these F–C reactions. This

new metal-free approach for the catalytic and stereoselective

alkylation of electron-rich arenes proved to be general in

scope, and polyalkylation, which is the main type of side

reaction in the metallocatalyzed addition of arenes to

aldehydes, was not observed. Finally, the stereo-

selective 1,4-addition of indoles to crotonaldehyde

in the presence of 27 b led to a very useful synthetic

application of this strategy, allowing the synthesis of indolobutyric acid 29 (COX-2 inhibitor) in good

yield and good optical purity (Scheme 17).

The aforementioned organocatalysis protocol is

ineffective toward the stereoselective addition of

aromatic compounds to a,b-unsaturated ketones,

which are less reactive than the corresponding

aldehydes. We recently investigated the use of the

chiral [Al(salen)Cl] complex 31 in the presence 2,6-

lutidine as the catalyst for the first enantioselective

addition of indoles to a,b-unsaturated aryl ketones

(up to 89% ee, Scheme 18). Experimental evidence

suggests that a new catalytic species, formed by

Scheme 13. Enantioselective conjugate addition of indoles to b,g-unsa-turated a-ketoesters in the presence of the cationic tBu-box–copper(ii)complex 17.

Scheme 14. Versatility of new chiral trisoxazoline ligands in the Michael addition of indole toalkylidene and arylidene malonates. The sidearm effect.

Scheme 15. Examples of enantioselective organocatalyzed Friedel–Crafts Michael-type addition of pyrroles, indoles, and anilines to a,b-

unsaturated aldehydes.







complexation of the aluminum complex with the amine,

operates in the enantiodiscrimination step of the F–C

alkylation.

5. Summary and Outlook

As we have seen herein, the design and development of

new catalytic and stereoselective strategies for the alkylation

of aromatic compounds have received a great deal of

attention in recent years. These strategies, which overcomethe historical drawbacks of a lack in regio- and chemo-

selectivity associated with Friedel–Crafts alkylations, allow

easy access to several classes of polyfunctionalized enantio-

merically enriched compounds, which are valuable building

blocks in organic synthesis.[26] These reactions are undergoing

continuous development. The attempt to extend the applic-

ability of catalytic stereoselective protocols to less reactive

aromatic compounds is only one of the challenges that engage

researchers on a daily basis in one of the oldest reactions of

modern organic synthesis.

Received: July 10, 2003 [M1679]

[1] a) C. Friedel, J. M. Crafts, C. R. Hebd. Seances Acad. Sci. 1877,

84, 1392; b) C. Friedel, J. M. Crafts, C. R. Hebd. Seances Acad.

Sci. 1877, 84, 1450.

[2] a) G. A. Olah in Friedel-Crafts and Related Reactions, Wiley,

New York, 1963 ; b) G. A. Olah in Friedel-Crafts Chemistry,

Wiley, New York, 1973.

[3] a) T. Tsuchimoto, K. Tobita, T. Hiyama, S. Fukuzawa, J. Org.

Chem. 1997, 62, 6997 – 7005; b) S. Gmouh, H. Yang, M. Vaultier,

Org. Lett. 2003, 5, 2219– 2222.

[4] Based on a survey of the SciFinder Scholar (ACS), CARPLUS,

and MEDLINE databases.

[5] a) F. Bigi, G. Casiraghi, G. Casnati, G. Sartori, J. Org. Chem.

1985, 50, 5018– 5022; b) G. Erker, A. A. H. van der Zeijden,

Angew. Chem. 1990, 102, 562–565; Angew. Chem. Int. Ed. Engl.

1990, 29, 512–514.

[6] For a recent overview of asymmetric F–C reactions, see: Y.

Wang, K. Ding, L. Dai, Chemtracts 2001, 14, 610–615.

[7] For representative examples of Lewis acid catalyzed F–C

alkylations, see: a) S. K. Taylor, S. A. May, E. S. Stansby, J.

Org. Chem. 1996, 61, 2075– 2080; b) R. Reddy, J. B. Jaquith,

V. R. Neelagiri, S. Saleh-Hanna, T. Durst, Org. Lett. 2002, 4,

695– 697; c) S. Nagumo, I. Miyoshi, H. Akita, N. Kawahara,

Tetrahedron Lett. 2002, 43, 2223– 2226.[8] H. Kotsuki, K. Hayashida, T. Shimanouchi, H. Nishizawa, J. Org.

Chem. 1996, 61, 984 – 990.

[9] a) B. C. Ranu, Eur. J. Org. Chem. 2000, 2347 – 2356; b) K. K.

Chauhan, C. G. Frost, J. Chem. Soc. Perkin Trans. 1 2000, 3015 –

3019.

[10] M. Bandini, P. G. Cozzi, P. Melchiorre, A. Umani-Ronchi, J. Org.

Chem. 2002, 67 , 5386– 5389.

[11] M. Bandini, P. G. Cozzi, P. Melchiorre, A. Umani-Ronchi,

Angew. Chem. 2004, 116, 86–89; Angew. Chem. Int. Ed. 2004,

43, 84–87.

[12] G. A. Olah, R. Khrisnamurti, G. K. Surya Prakash, Comprehen-

sive Organic Synthesis, Vol. 3, 1st ed., Pergamon, New York,

1991, pp. 293– 339.

[13] For homogeneous catalysis, see: a) J. S. Yadav, B. V. Subba

Reddy, Ch. V. S. R. Murthy, G. Mahesh Kumar, Ch. Madan,Synthesis 2001, 783– 787; b) J. Hao, S. Taktak, K. Aikawa, Y.

Yusa, M. Hatano, K. Mikami, Synlett 2001, 1443–1445; for

heterogeneous catalysis, see: C. Ramesh, J. Banerjee, R. Pal, B.

Das, Adv. Synth. Catal. 2003, 345, 557–559.

[14] a) M. Johannsen, Chem. Commun. 1999, 2233– 2234; b) A. Ishii,

V. A. Soloshonok, K. Mikami, J. Org. Chem. 2000, 65, 1597–

1599.

[15] K. Mikami, S. Matsukawa, Nature 1997, 385, 613– 615.

[16] a) S. Saaby, X. Fang, N. Gathergood, K. A. Jørgensen, Angew.

Chem. 2000, 112, 4280–4282; Angew. Chem. Int. Ed. 2000, 39,

4114 – 4116; b) S. Saaby, P. Bayn, P. S. Aburel, K. A. Jørgensen,

J. Org. Chem. 2002, 67 , 4352– 4361.

[17] a) N. Gathergood, W. Zhuang, K. A. Jørgensen, J. Am. Chem.

Soc. 2000, 122, 12517 – 12522; b) W. Zhuang, N. Gathergood,

R. G. Hazell, K. A. Jørgensen, J. Org. Chem. 2001, 66, 1009–

1013.

[18] Very recently an interesting stereoselective tandem oxa-Michael

addition/Friedel–Crafts alkylation was reported for the synthesis

of functionalized chromanes: H. L. van Lingen, W. Zhuang, T.

Hansen, F. P. J. T. Rutjes, K. A. Jørgensen, Org. Biomol. Chem.

2003, 1, 1953– 1958.

[19] A. Corma, H. Garca, A. Moussaif, M. J. Sabater, R. Zniber, A.

Redouane, Chem. Commun. 2002, 1058– 1059.

[20] For examples, see: a) P. E. Harrington, M. A. Kerr, Synlett 1996,

1047– 1048; b) K. Manabe, N. Aoyama, S. Kobayashi, Adv.

Synth. Catal. 2001, 343, 174 – 176; c) M. Bandini, P. G. Cozzi, M.

Giacomini, P. Melchiorre, S. Selva, A. Umani-Ronchi, J. Org.

Chem. 2002, 67 , 3700– 3704; d) M. Bandini, P. Melchiorre, A.

Scheme 16. The LUMO-lowering activation of a,b-unsaturated

aldehydes by formation of chiral iminium salts 28.

Scheme 17. Organocatalyzed Friedel–Crafts alkylation for the synthesisof the COX-2 inhibitor 29.

Scheme 18. Enantioselective Michael-type addition of indoles to a,b-unsaturated aryl ketones catalyzed by an [Al(salen)Cl]/2,6-lutidine com-plex.


Chemie






Melloni, A. Umani-Ronchi, Synthesis 2002, 1110–1114; e) M.

Bandini, M. Fagioli, A. Melloni, A. Umani-Ronchi, Synthesis

2003, 397 – 402; f) N. Srivastava, B. K. Banik, J. Org. Chem. 2003,

68, 2109– 2114.

[21] K. B. Jensen, J. Thorhauge, R. G. Hazell, K. A. Jørgensen,

Angew. Chem. 2001, 113, 164–167; Angew. Chem. Int. Ed. 2001,

40, 160–163.

[22] J. Zhou, Y. Tang, J. Am. Chem. Soc. 2002, 124, 9030– 9031.

[23] W. Zhuang, T. Hansen, K. A. Jørgensen, Chem. Commun. 2001,

347–348.

[24] a) N. A. Paras, D. W. C. MacMillan, J. Am. Chem. Soc. 2001, 123,

4370 – 4371; b) J. A. Austin, D. W. C. MacMillan, J. Am. Chem.

Soc. 2002, 124, 1172 – 1173; c) N. A. Paras, D. W. C. MacMillan,

J. Am. Chem. Soc. 2002, 124, 7894– 7895.

[25] M. Bandini, M. Fagioli, P. Melchiorre, A. Melloni, A. Umani-

Ronchi, Tetrahedron Lett. 2003, 44, 5846– 5849.

[26] Some b-indolyl esters and b-indolyl aldehydes are currently

commercially available in enantiomerically pure form; see:

www.materia-inc.com.





new catalyst in asymetric

Documents