Of chiral P-lactams

Some other chiral Nylon 3 analogs have also been prepared by the same authors applying ring-opening polymerization of chiral p-lactams 84 derived from D-glyc-eraldehyde [70,71], The enantiomerically pure (2R,3R) and the racemic (2R,3R and 2S,3S) p-polyamides were obtained, and their properties compared. 

Instead, complexes with chiral chelates of the 2,2 -bipyridine (bpy) ligand could lead to asymmetric induction in the synthesis of chiral p-lactams. 

A route to chiral oxazolidinones reported last year (Vol. 23, p. 272) has been extended to the preparation of chiral p-lactams such as (96), which are potential precursors of carbapenems the oxazolidinones were opened reductively to P-aminoacids and then recyclized using 2-chloro-l-methyl-pyridinium iodide.72... 

Sekine, A., Hori, K., Ohashi, Y, Yagi, M., and Toda, R, X-ray structural studies of chiral P-lactam formation from an achiral oxo amide using the chiral-crystal environment,/.Am. Chem. Soc., Ill, 697, 1989. 

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

You and co-workers have demonstrated a further application of NHCs in the kinetic resolution of formyl p-lactams ( )-265 [103]. Upon treatment with a chiral NHC, the Breslow-type intermediate is formed, followed by ring-opening of the P-lactam moiety, with subsequent trapping of the acylazolium intermediate leading to the enantio-enriched succinimide product 266 and resolved formyl P-lactam (which is reduced to its alcohol 267). The authors note that when R" = H, the products undergo racemisation readily, and this is a possible explanation for the lower levels of enantioselectivity observed in the succinimide products 266 (Scheme 12.60). 

A chiral p-polyamide 83 of the Nylon 3 type was also synthesized [68, 69] by Galbis et al. by ring-opening polymerization of the p-lactam derived from 3-amino-3-deoxy-2,4,5,6-tetra-(9-methyl-D-altronic acid. 

While sluggish under thermal conditions,274-275 the asymmetric conjugate addition of amines to alkyl crotonates is achieved at room temperature under high pressure (15 kbar).276 Thus, benzylamine can be added to the crotonate derived from 8-p-naphthyl menthol, with virtually complete diastereoselectivity. A related intramolecular 1,4-addition of an amine to a chiral enoate was used in a total synthesis of the alkaloid (-)-tylophorine.277 Additions of amines to chiral iron complexes of type (116) proceed with excellent selectivity and allow the preparation of homochiral p-lactams.l27128,l3() l32 In contrast, the addition of amine nucleophiles to chiral vinylic sulfoxides278-2811 and to chiral vinylsulfoximines281 proceeds with comparably low selectivities. 

Enantioselective synthesis of analogous p-lactams has been also reported [63]. If the starting imine complex was prepared from the corresponding chiral amine in enantiomerically pure form (Fig. 1), two separable diastereomers were obtained. Using, then, one of the two diastereomers, ck-p-lactams were isolated as single enantiomers. 

Scheme 24 Asymmetric synthesis of cw-P-lactams starting from chiral imines derived from D-(+)-glucose...

Gallop et al. [80] reported the preparation of p-lactams via a [2+2] cycloaddition reaction of ketenes with resin-bound imines derived from amino acids (Scheme 9). This is another solid-phase adaptation of the Staudinger reaction, which could lead to the synthesis of structurally diverse 3,4-bis-substituted 2-azetidinones [81]. In addition, a novel approach to the synthesis of A-unsubstituted-p-lactams, important building blocks for the preparation of p-lactam antibiotics, and useful precursors of chiral p-amino acids was described [82]. 

A related radical addition/5-exo cyclization cascade involving addition of sulfonyl radicals to alkynes has been used for the diastereoselective synthesis of bicyclic p-lactams 182 from the p-lactamic enyne precursor 181 (Scheme 2.33). In this radical chain sequence, where tosyl bromide is used as source of sulfonyl radicals, the final product is a mixture of epimers (90 10) at the newly formed exocyclic chiral center. 

An alternative route to chiral p-lactams was provided by reactions of electron-deficient isocyanates with chiral nucleophilic alkenes such as vinyl ethers or vinyl acetates. Chlorosulfonyl isocyanate (CSI), a commonly used reactive isocyanate [34], undergoes stereospecific 5-yn-addition to alkenes. The chlorosulfonyl group can subsequently be reductively removed from the nitrogen atom. It has been shown that reactions between CSI and (Z)- and ( )-alkenyl ethers stereoselectively give cA-3,4-disubstituted azetidinones from (Z)-olefins and tmns-3,4-... 

Degnan, A. P., Meyers, A. I. Total Syntheses of (-)-Herbertenediol, (-)-Mastigophorene A, and (+)-Mastigophorene B. Combined Utility of Chiral Bicyclic Lactams and Chiral Aryl Oxazolines. J. Am. Chem. Soc. 1999,121,2762-2769. 

Lin, S., Geng, X., Qu, C., et al. (2000) Synthesis of highly potent second-generation taxoids through effective kinetic resolution coupling of racemic P-lactams with baccatins. Chirality 12, 431—441. 

Most of the ionic chiral auxiliary-mediated reactions presented in Table 4 occur with very respectable ees, even at quite high conversions. The best of these in terms of overall optical and chemical yield is the reaction shown in entry 4, which gives an essentially quantitative GC yield of the p-lactam photoproduct with an ee of 99%. For a variety of practical reasons, and because modern methods of analysis do not require large sample sizes, all but one of the reactions in Table 4 were carried out on a microscale (< 10 mg). The lone exception was reaction 4, which could easily be scaled up to the 500 mg level to afford an ee of 99% with an isolated chemical yield of 91% [21]. This was done by irradiating the salt... 

The use of chiral sulfoxitnines 1.136 (R = Ph, Tol, Y = ArCH=N) has allowed the enantioselective synthesis of p-aminoesters after cleavage of the S-N bond by CF3COOH [510], Preliminary studies showed that the reaction of C-arenechromium tricarbonyl imines and the lithium enolate of Me2CHCOOEt gave chiral p-lactams after decomplexation with an excellent enantiomeric excess [549, 1291]. 

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