Diastereoselectivity Staudinger reaction

Besides imines bearing a chiral (l-naphthyl)-ethyl group, glycosylamine-derived imines as well as amino acid ester derivatives have been examined as chiral inductors in diastereoselective Staudinger reactions. 

Aldehydes with chiral a-alkoxy substituents may be derived from a-hydroxy acids, sugars, and other chiral pool fragments such as sodium erythorbate. Highly diastereoselective Staudinger reactions have been reported with these imines as well. Glyceraldehyde imines have also been used to provide P-lactam products with high diastereoselectivity, as shown below. Cyclic imines, such as enantiomerically pure dihydropyrazinones ... 

Lee EC, Hodous BL, Bergin E, Shih C, Fu GC (2005) Catalytic asymmetric Staudinger reactions to form P-lactams an unanticipated dependence of diastereoselectivity on the choice of the nitrogen substituent. J Am Chem Soc 127 11586-11587... 

Guama et al. [133] have employed unsymmetrical bicyclic ketene in the Staudinger reaction for diastereoselective synthesis of highly constrained... 

In 2001, p-lactams have been reported to be obtained via Staudinger reaction with complete m-diastereoselection starting from prochiral imine chromium complexes (Scheme 14), [63]. 

In 2004, bis-(cyclophanyldiol)A10Tf complex has been reported to catalyze the enantio- and diastereoselective synthesis of (3-lactams via Staudinger reaction (Scheme 25), [87]. 

The Staudinger reaction between enantiopure 5.6-di hydropvrazin-2-(7// )-ones and an excess of 2-heterosubstituted acetylchloride in the presence of triethylamine in dichloromethane at room temperature has been reported to produce in excellent yield and high diastereoselectivity fused oxopiperazino-(3-lactams (Scheme 39), [114],... 

Disubstituted [S-lactams have been obtained with high trans diastereoselection in the reaction between /V-phenylsulfenyl imines, as nucleophilic partners in the Staudinger reaction, and acetoxyacetyl chloride (Scheme 42), [117]. 

V-Heterocyclic carbenes were demonstrated to be efficient catalysts for the Staudinger reaction of ketenes with /V-aryl-, /V-alkylcarbonyl imines [121]. Chiral /V-heterocyclic carbenes gave the corresponding < /.v-(3-lactams in good yields with good diastereoselectivities and excellent enantioselectivities (ee>99%). 

One method for the synthesis of hydroxyalkyl-substituted P-lactams is by the Staudinger reaction, the most frequently used method for the synthesis of P-lactams.86 This method for the preparation of 4-acetoxy- and 4-formyl-substituted P-lactams involves the use of diazoketones prepared from amino acids. These diazoketones are precursors for ketenes, in a diastereoselective, photochemically induced reaction to produce exclusively tram-substituted P-lactams. The use of cinnamaldimines 96, considered as vinylogous benzaldimines, resulted in the formation of styryl-substituted P-lactams. Ozonolysis, followed by reductive workup with dimethyl sulfide, led to the formation of the aldehyde 97, whereas addition of trimethyl orthoformate permitted the production of the dimethyl acetal 98 (Scheme 11.26). 

Staudinger Reactions. Chiral oxazolidinones have been employed as the chiral control element in the Staudinger reaction as well as the ultimate source of the a-amino group in the formation of p-lactams." Cycloaddition of ketene derived from 4-(S)-phenyloxazolidylacetyl chloride with conjugated imines affords the corresponding p-lactams in 80-90% yields with excellent diastereoselectivity (eq 54). The auxiliary can then be reduced under Birch conditions to reveal the a-amino group. 

Sulfimines 175 are obtained in excellent yield by Staudinger condensation of sulfin-amide 174 with trifluoropyruvates. In contrast, and quite surprisingly, the Staudinger reaction of terf-butylsulfinamide 182 with the pyruvates under the same conditions does not work. Sulfimines 175 are alkylated with Grignard reagents in good yields but with poor to moderate diastereoselectivities (see Scheme 9.39) [67]. 

Ionic liquids have been proved to be efficient pre-catalysts (in solution of THF, containing 10% Cs COj) in the Staudinger reaction of arylalkylketenes with a variety of N-t-butoxycarbonyl arylimines to give the corresponding P-lactams in good yields with good diastereoselectivity and enantioselectivity (Scheme 16.8) [96]. 

The j -lactam nucleus can also be assembled efficiently by a ketene-imine cycloaddition known as the Staudinger reaction. The reaction of chiral imine 759 with alkoxyketenes generated tfom benzyloxyacetyl chloride or acetoxyacetyl chloride affords cw-3,4-di-substituted )S-lactams 764a (75% yield) or 764b (61% yield) with diastereoselectivities greater than 95% [218]. 

Oxazolidinone aiudharies based on o-xylose [66] and D-mannitol [67] residues were converted into corresponding carboxylic acids 79 and 80 which after activation were used for stereoselective Staudinger reaction with diaryl, or aryl-styryl imines. hi the first case, an excellent diastereoselectivity was obtained to afford 81 with high preponderance [66]. hi the second case. 

In 2008, Ye and coworkers reported that chiral NHCs prepared from l-pyroglutamic acid were efficient catalysts for the enantioselective Staudinger reaction of ketenes with imines. The corresponding c/s-p-lactams 158 were obtained in good yields with good diastereoselectivities and excellent enantioselectivities (up to 99% ee) (Scheme 20.66). In the same year. Smith and coworkers independently reported the NHC-catalysed [2 + 2] cycloaddition of disubstituted ketenes and N-tosylimines. ... 

The reaction of a monosubstituted ketene with an aldimine produces two new stereocenters, C3 and C4, in the P-lactam ring. The substituents on these two carbon atoms may therefore be cis or trans to each other, and the reaction of any particular pair of ketene and imine may afford the cis P-lactam, the tra 5-P-lactam, or a mixture of the two. The importance of P-lactams as antibacterial agents has resulted in extensive effort to understand the diastereoselectivity of the Staudinger reaction. The two-step nature of the reaction pathway has made the interpretation of experimental results more difficult and increased the number of possible contributing factors. 

Chiral ketene fragments have proven to offer more general utility in the quest for enantioselective Staudinger reactions. In particular, ketenes containing the Evans oxazolidinone have proven to offer high diastereoselectivities in the synthesis of 3-amino-P-lactams. The ease of preparation of the carboxylic acid precursor, the low cost of the auxiliary, and the facile unmasking of the 3-amino group from the auxiliary all... 

The two-component nature of the Staudinger reaction suggests that double asymmetric induction may afford improved diastereoselectivity. The chiral groups may be paired in any of three ways (1) a chiral aldehyde with a chiral amine to place two defined stereocenters on the imine, (2) an imine with a chiral A -substituent with a chiral ketene substituent, and (3) an imine with a chiral C-substituent with a chiral ketene. Some examples of these possibilities have been reported. 

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