Enantioselective synthesis of a-amino

An application of this method is the enantioselective synthesis of a-amino acids [e.g., (5)-phenyl-glycine (11)]10. Hence, 8 can be regarded as a chiral synthetic equivalent of a carboxyl group. 

To complement the above information, a highly enantioselective synthesis of a-amino phosphonate diesters should be mentioned.164 Addition of lithium diethyl phosphite to a variety of chiral imines gives a-amino phosphonate with good to excellent diastereoselectivity (de ranges from 76% to over 98%). The stereoselective addition of the nucleophile can be governed by the preexisting chirality of the chiral auxiliaries (Scheme 2-63). 

Corey, E. J. Grogan, M. J. Enantioselective Synthesis of a-Amino Nitriles from N-Benzhydryl Imines and HCN with a Chiral Bicyclic Guanidine as Catalyst Org Lett. 1999,1,157-160. 

B. Lygo, P. G. Wainwright, A New Class of Asymmetric Phase-Transfer Catalysts Derived from Cinchona Alkaloids - Application in the Enantioselective Synthesis of a-Amino Acids , Tetrahedron Lett., 1997, 38, 8595-8598. 

M J. O Donnell, F. Delgado, C. Hostettler, R, Schwesinger, An Efficient Homogeneous Catalytic Enantioselective Synthesis of a-Amino Add Derivatives , Tetrahedron Lett. 1998,39, 8775-8778. 

By employing A-acetamidoacrylates, rhodium-catalyzed 1,4-addition reactions can be applied to the enantioselective synthesis of a-amino acids. Unlike other typical 1,4-addition reactions, which install a stereogenic center at the p-position of the 1,4-adducts, this process deals with the formation of a stereocenter at the a-position, and thus the protonation (hydrolysis) step becomes an important step... 

The enantioselective synthesis of a-amino acids is an important goal in preparative organic chemistry89. The use of l,3-oxazolidin-5-ones for this purpose has already been shown. A number of examples utilizing six-membered heterocycles exist whereby the basic idea remains the same i.e., the nonracemic enolate is attacked preferentially from the less hindered side because of a built-in auxiliary bias which can be removed in the alkylation step in order to liberate the nonracemic a-amino acid90. 

Scheme 9.4 Enantioselective synthesis of a-amino acids via catalytic asymmetric hydrogenation ofenamides.

Scheme 17 illustrates enantioselective synthesis of a-amino acids by phase-transfer-catalyzed alkylation (46). Reaction of a protected glycine derivative and between 1.2 and 5 equiv of a reactive organic halide in a 50% aqueous sodium hydroxide-dichloromethane mixture containing 1-benzylcinchoninium chloride (BCNC) as catalyst gives the optically active alkylation product. Only monoalkylated products are obtained. Allylic, benzylic, methyl, and primary halides can be used as alkylating agents. Similarly, optically active a-methyl amino acid derivatives can be prepared by this method in up to 50% ee. 

In a related contribution O Brien described the AA on styrenes and converted the amino alcohols into enantiopure diamines by using a reaction strategy similar to Janda s [83], Further synthetic applications of the AA include a new access to Evans chiral oxazolidinones [84], the enantioselective synthesis of a-amino ketones from silyl enol ethers [85], the stereoselective synthesis of cyclohexyl norstatine [86], and a route towards amino cyclitols by aminohydroxy-lation of dienylsilanes [87]. 

The enantioselective synthesis of a-amino acids employing easily available and reusable chiral catalysts or reagents presents clear advantages for large-scale applications. Accordingly, recyclable fluorous chiral phase-transfer catalyst 31 has been developed by the authors group, and its high chiral efficiency and reusability demonstrated in the asymmetric alkylation of 2. After the reaction, 31 could be easily recovered by simple extraction with FC-72 (perfluorohexanes) as a fluorous solvent and used for the next run, without any loss of reactivity and selectivity (Scheme 5.17) [23]. 

Similarly, the reaction of alkenyl boronic acids with azomethines can be found. Indeed, the corresponding 3-CR was used by Petasis [33] for the enantioselective synthesis of a-amino acids starting from amines, a-keto acids and alkenyl boronic acids. 

A BINOL-derived phosphoric acid derivative has been used as a catalyst in the enantioselective synthesis of a-amino phosphonates via hydrophosphonylation of imines with diisopropyl phosphite.82... 

A new diastereoselective and enantioselective synthesis of a-amino-y-oxo acid esters has been reported involving the alkylation of enamines with acyliminoacetates (78). The stereocontrol is attributed to formation of a Diels-Alder like transition state (79). Ring opening of the adduct leads to a zwitterion or alkylated enamine, hydrolysis of which gives the single diastereoisomer (80 de > 96%)174 (Scheme 71). The use of a chiral ester [R = ( + )- or ( —)-menthyl or (—)-8-phenylmenthyl] converted this process into an enantioselective reaction (de and ee 24-67%). Since the reaction proceeds with complete anti-diastereoselectivity the two stereoisomers, enantiomeric at the two new stereogenic centres, could readily be separated by fractional crystallization. The main isomer of 80 (X = CH2), obtained in 80% yield, was shown to have the (l S, 2R)-configuration174. 

Maruoka K, Ooi T. Enantioselective amino acid synthesis by chiral phase-transfer catalysts. Chem. Rev. 2003 103 3013-3028. O Donnell MJ. The enantioselective synthesis of a-amino acids by phase-transfer catalysis with achiral Schiff base esters. Acc. Chem. Res. 2004 37 506-517. 

Reviews on phase-transfer catalysis for the syntheses of a-amino acids, (a) Ooi, T. and Maruoka, K. (2004) Asymmetric organocatalysis of structurally well-defined chiral quaternary ammonium fluorides. Acc. Chem. Res., 37, 526-533 (b) Maruoka, K. and Ooi, T. (2003) Enantioselective amino acid synthesis by chiral phase-transfer catalysis. Chem. Rev., 103, 3013-3028 (c) Ooi, T. and Maruoka, K. (2003) Enantioselective synthesis of a-amino acids by chiral phase-transfer catalysis. Yuki Gosei Kagaku Kyokaishi (J. Synth. Org. Chem.) 61, 1195-1206. 

Soon after these initial reports, the groups of Antilla [92] and You [93] indepen dently applied the chiral phosphoric acid catalysis to the enantioselective hydro genation of a imino esters. The method provides an alternative route to the enantioselective synthesis of a amino esters. Antilla and coworkers employed a new type of axially chiral phosphoric acid (9) derived from VAPOL originally developed by his research group (Scheme 3.42), whereas lg was used in You s case. In both cases, excellent enantioselectivities were achieved. You and coworkers further applied the method to the enantioselective reduction of a imino esters having an alkynyl substituent at the a position (Scheme 3.43) [94]. Both alkyne and imine moieties were reduced under transfer hydrogenation conditions with an excess amount of... 

Durham TB, MiUer Ml (2003) Enantioselective synthesis of a-amino acids from N-tosyloxy P-lactams derived from P-keto esters. J Org Chem 68 27-34... 

Enantioselective synthesis of a-amino acids A practical and general route to a-amino acids involves enantioselective reduction of alkyl trichloromcthyl ketones with catccholboranc (CB) in the presence of the oxazaborolidine (S)-l (0.1 cquiv.) to give (R)-alcohols 2. The (R)-alcohols (2) arc converted on treatment with NaOH... 

The use of optically resolved PTC catalysts for the synthesis of enantiomerically pure compounds is no doubt an attractive field. Asymmetric PTC has become an important tool for both laboratory syntheses and industrial productions of enantiomerically enriched compounds. Recently, Lygo and coworkers [207-216] reported a new class of Cinchona alkaloid-derived quaternary ammonium PTC catalysts, which have been applied successfully in the enantioselective synthesis of a-amino acids, bis-a-amino acids, and bis-a-amino acid esters via alkylation [207-213] and in the asymmetric epoxidation of a/p-unsaturated ketones [214-216]. 

This reaction was first reported by Corey and T.ink in 1992. It is an enantioselective synthesis of a -amino acids by means of the asymmetric reduction of trichloromethyl ketones from catechoiborane in the presence of either (/ )- or (5)-oxazaborolidine, followed by the treatment of the resulting alcohols with base and sodium azide and subsequently the reductive conversion of the azido group into an amino group. Therefore, this reaction is generally known as the Corey-Link reaction. Occasionally, it is also referred to as the Corey-Link amino acid synthesis, Corey-Link procedure, etc. 

O Donnell MJ (2004) The Enantioselective Synthesis of a-Amino Acids by Phase-Transfer Catalysis with Achiral Schijf Base Esters. Acc Chem Res 37 506... 

A highly enantioselective synthesis of a-amino acid derivatives employs an NHC-catalysed intermolecular Stetter reaction of an o, /3-unsaturated ester with an aldehyde. The key steps of (i) C-C bond formation between Breslow intermediate 0 and Michael acceptor and (ii) asymmetric protonation are efficiently combined, giving ees of 85-99%. 

The most general protocol (eq 10) has therefore been based on potassium hexamethyldisilazide (KHMDS) as the base addition of trisyl azide at —78 °C and then acetic acid at the same temperature. Excellent levels of diastereoselectivity are ohsCTved with most substrates and the method has been used widely in the enantioselective synthesis of a-amino acids from chiral iniides. Chemoselective azidation of an imide enolate in the presence of an ester function has been demonstrated (eq 11). The product distribution is nevertheless finely balanced, as discovered with the respective dimethyl and dihenzyl ethers of the 3,5-substituted phenylacetyl imide (3) (eq 12). ... 

An optimised chiral binol phosphate catalyst (87) for the hydrocyanation of imines provides a convenient strategy for the enantioselective synthesis of a-amino acids and diamines (Scheme 22). The same catalyst (87) has been used for cascade... 

Scheme 11.13 Enantioselective synthesis of a-amino ester derivatives by 50.

Muralidharan KR, MokhaUalati MK, Pridgen LN. Enantioselective synthesis of a-amino acetals (aldehydes) via nucleophilic 1,2-addition to chiral 1,3-oxazolidines. Tetrahedron Lett. 1994 35 7489-7492. 

Jousseaume T, Wurz NE, Glorius F. Highly enantioselective synthesis of a-amino acid derivatives by an NHC-catalyzed intermolecular Stetter reaction. Angew. Chem. Int. Ed. 2011 50(6) 1410-1414. 

Yokomatsu T, Shibuya S (1992) Enantioselective synthesis of a-amino phosphonic acids by an application of stereoselective opening of homochiral dioxane acetals with triethyl phosphite. Tetrahedron Asym 3 377-378... 

Groger H, Hammer B (2000) Catalytic concepts for the enantioselective synthesis of a-amino and a-hydroxy phosphonates. Chem Eur J 6 943-948... 

---