Lactams asymmetric

Chiral bicyclic lactams as useful precursors and templates for asymmetric syntheses 97CC1. 

Asymmetric synthesis of 3-amino (3-lactams via Staudinger ketene-imine cycloaddition reaction 98KGS1448. 

Whereas there are numerous examples of the application of the products from diastereoselective 1,3-dipolar cycloaddition reaction in synthesis [7, 8], there are only very few examples on the application of the products from metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction in the synthesis of potential target molecules. The reason for this may be due to the fact that most metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction have been carried out on model systems that have not been optimized for further derivatization. One exception of this is the synthesis of a / -lactam by Kobayashi and Kawamura [84]. The isoxazoli-dine endo-21h, which was obtained in 96% ee from the Yb(OTf)3-BINOL-catalyzed... 

Intermolecular Schmidt reactions of alkyl azides and hydroxyalkyl azides with cycloketones in the presence of a Lewis acid, lead to formation of iV-alkyl lactams and A-hydroxyalkyl lactams respectively in good yield. The synthesis of chiral lactams by an asymmetric Schmidt reaction has also been reported. ... 

A chiral sulfoxide can be used as a leaving group for the asymmetric inducdon via addidon-eliminadonprocess. 5-Lactam enolates are converted into the corresponding nitroalkenes subsdnited with lactams fEq. 4.101. ... 

Reaction of p-nitrophenyl 2-(p-tolylsulfinyl)acetate 161 with aryl aldimines in the presence of imidazole was found to give /j-lactams 162 and amides 163206. In the cyclization, only the two 3,4-trans derivatives were formed out of a possible four diastereomeric pairs and, interestingly, the ratio of two diastereomeric pairs went up to 6.7 1. This means not only that internal asymmetric induction207 affords the trans derivative, but that also a relatively high asymmetric induction took place during the reaction. 

Diastereoselective alkylation of lactams derived from 7 -(-)-phenylglycinol is an efficient method for the preparation of various substituted piperidines <961(52)7719, 961(52)7727, 961L(37)849>. Ihe asymmetric s mthesis of a series of 2-(l-aminoalkyl)piperidines using (-)-2-cyano-6-phenyloxazolopiperidine has been described <96JOC(61)6700>. 

The Staudinger reaction [92], a [2 + 2]-cycloaddition of a ketene and a nucleophilic imine, usually proceeds by an initial imine attack on the ketene thus forming a zwitterionic enolate which subsequently cyclizes. This reaction is an expedient route to p-lactams, the core of numerous antibiotics (e.g., penicillins) and other biologically active molecules [93]. In contrast, for Lewis-base catalyzed asymmetric reactions, nonnucleophilic imines are required (to suppress a noncatalyzed background reaction), bearing, for example, an N-Ts [94] or -Boc-substituent [95]. 

Fig. 40 Formation of (3-lactams via asymmetric Staudinger-type reactions, catalyzed by 64c...

Taggi AE, Hafez AM, Wack H, Young B, Ferraris D, Lectka T (2002) The development of the first catalyzed reaction of ketenes and imines catalytic, asymmetric synthesis of P-lactams. J Am Chem Soc 124 6626-6635... 

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... 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

Scheme 12.43 Asymmetric 3-lactam synthesis using chiral NHCs...

Ojima, 1., Habus, 1., Zhao, M. (1991) Efficient and Practical Asymmetric Synthesis ofthe Taxol C-13 Side Chain, N-Benzoyl-(2R,3S)-3-phenylisoserine, and its Analogues via Chiral 3-Hydroxy-4-aryl-b-lactams Through Chiral Ester Enolate-Imine Cyclocondensation. Journal of Organic Chemistry, 56, 1681-1683. 

In 1999, this methodology was applied to the synthesis of unnatural biologically active ( + )-5-epi-nojirimycin-5-lactam, a potent and selective glycosidase inhibitor.The key step of this synthesis was the asymmetric reduction of a cyclic triacetyloxy meso imide under the same conditions to those described above, which resulted in the formation of the corresponding hydroxy 5-lactam in good yield and enantioselectivity of 85% ee (Scheme 10.59). 

A radical approach to asymmetric aldol synthesis, which is based on the radical addition of a chiral hydroxyalkyl radical equivalent to a nitroalkene, has been reported, as shown in Eq. 4.93.113 The radical precursor is prepared from the corresponding carboxylic add by the Barton reaction,114 which has been used for synthesis of new (3-lactams.115... 

---