3- Substituted -sultams, asymmetric synthesis

An efficient asymmetric synthesis of the 3-substituted /3-sultams 163 has been reported. The key step of the synthesis is the Lewis acid-catalyzed aza-Michael addition of the enantiopure hydrazines (A)-l-amino-2-methoxy-methylpyrrolidine (SAMP) or CR,l ,l )-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]octane (RAMBO) to the alke-nylsulfonyl sulfonates 176. /3-Hydrazino sulfonates were obtained in good yield and excellent enantioselectivity. Cleavage of the sulfonates followed by chlorination resulted in the corresponding sulfonyl chlorides 177. The (A)-3-substituted /3-sultams 163 have been obtained in moderate to good yields and high enantioselectivity over two steps, an acidic N-deprotection followed by in situ cyclization promoted by triethylamine (Scheme 55) <2002TL5109, 2003S1856>. 

An efficient asymmetric synthesis of the 3-substituted -sultams 34 in high enantioselectivity includes an acidic N-deprotection of sulfonyl chlorides 33 followed by in situ cyclization promoted by triethylamine (Scheme 22) <2002TL5109, 2003S1856>. 

The asymmetric synthesis of c -3,4-disubstituted P-sultams 65, based on the oxidation of 1,2-aminothiols with H2O2 and ammonium heptamolybdate has been achieved <05S1807>. Different transition-state structures for the reactions of P-lactams and their sulfonyl analogues P-sultams with serine P-lactamases have been reported <05JA17556>. It has been discovered that the 3-oxo-P-sultam 66 is unusual in that it inhibits elastase by acylation resulting from substitution at the carbonyl center, C-N fission, and expulsion of the sulfonamide <05JA8946>. 

Another classic in asymmetric synthesis is Oppolzer s sultam 91 [48], and various JV-acyl derivatives 92 were used - inter alia - for diastereoselective alkylations. Early attempts for enolate generation from amides 92 were plagued by competing deprotonation at carbon 10, adjacent to the sulfonyl group, but regioselective metallation at the a-carbonyl position was achieved by treatment with -butyllithium, LICA, or NaHMDS. The method is applicable not only to the sultam derived from propionic acid 92 (R = Me) but also to substituted and... 

The Gabriel-Cromwell aziridine synthesis involves nucleophilic addition of a formal nitrene equivalent to a 2-haloacrylate or similar reagent [29]. Thus, there is an initial Michael addition, followed by protonation and 3-exo-tet ring-closure. Asymmetric variants of the reaction have been reported. N-(2-Bromo)acryloyl camphor-sultam, for example, reacts with a range of amines to give N-substituted (azir-idinyl)acylsultams (Scheme 4.23) [30]. 

Hanessian reported the synthesis of enantiomerically pure or highly enriched allylglycine and its chain-substituted analogs from the reaction of the sultam derivatives of O-benzyl glyoxylic acid oxime with ally he bromides in the presence of zinc powder in aqueous ammonium chloride (Eq. 11.41).72 Brown noticed the critical importance of water in the asymmetric allylboration of /V-trimethylsilyIbcnzaldimines with B-allyldiisopinocampheylborane.73 The reaction required one equivalent of water to proceed (Eq. 11.42). 

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