Reduction lactam

An asymmetric synthesis of 3,4,5-trisubstituted-tetrahydro-l-benzazepines has been reported based on a type a ring construction process mediated by triethylaluminium with a chiral amino ester followed by lactam reduction with borane <2006OL2667>. Dynamic thermodynamic resolution in a lithiation-substitution sequence was integral to the preparation of the amino ester. An acid-catalyzed ring construction approach to the asymmetric synthesis of 4,5,6-trisubstituted- and 3,4,5,6-tetrasubstituted azepanes based on chiral acyclic precursors has also been described <2006JA2178>. 

Access to chiral 1-substituted tetrahydro-3-benzazepines by aysmmetric sysnthesis has been reported <2007EJ0462>. The synthesis began with o-phenylenediacetic acid and (R)-phenylglycinol, and proceeded via an acid catalyzed type a ring constmction to afford an intermediate oxazolobenzazepinone. This intermediate in turn was then subjected to lactam reduction followed by hydrogenolytic removal of the N-substituent to afford the chiral reduced 3-benzazepines, which were evaluated as NMDA receptor antagonists. 

Other fused azepines, with aromatic (e.g. 94a,b) or heteroaromatic fused rings (e.g. 94c,d) have been prepared via the Af-acyliminium ion intermediate 93 in high yields lactam reduction then yielded the respective amines 95a,b and 95c,d [01H1519]. An intramolecular Friedel-Crafts reaction has been used to synthesise the fused azepinone 99 (S,S configuration) from 98, the latter being prepared from the diastereopure a-hydroxylactam 96, via the acid 97 [02H449],... 

An improved procedure for the rapid synthesis of aryl dihydrobenzofurans with a boron tribromide-mediated cyclization was discussed and is shown below <03HCA343>. In the second total synthesis of diazonamide A, the late key step accounting for the dihydrobenzofuran formation was a DIBAL-H mediated lactam reduction and cyclization <03AG(E)1753>. 

Other complex, chiral oxazolidines of this type have proved to be useful in natural product synthesis (Scheme 76). The epimeric esters 218 were separately converted to their respective O-benzylcarbinols 219. These were subjected to a desaturation-oxidation sequence to give 220. Lactam reduction followed by N- and 0-hydrogenolysis gave the azasugars 221 <04TL4903>. 

Kreher improved upon Welch s lactam reduction by using diisobutylaluminum hydride (DIBAL) to reduce either lactam (Scheme 14, equation 1) [80]. Srinivasan and Jeevanandam employed a route similar to Sha s [78] to prepare a series of 2,4-dihydropyrrolo[3,4- ]indoles 43 (equation 2) [81]. A Diels-Alder reaction of 43 (R=Me, R =Bn) with DMAD gave the cycloadduct in 70% yield, which on exposure to tosic acid yielded dimethyl 4-benzylamino-l-methyl-5-(phenylsulfonyl)carbazole-2,3-dicarboxylate (68% yield). Snyder and coworkers described a novel pyri-dazine reductive ring contraction, as explored by Boger... 

They introduced chirality on the a-methylpiperidine core in a biocatalytic transamination using a three-enzyme system with excellent enantioselectivity (>99% ee). Low diastereoselectivity of the lactam reduction was overcome by the development of a camphor sulfonic acid salt formatioa A chemoselective O-alkylation with 5-fluoro-2-hydroxypyridine was optimized and developed. Overall, 1.2 kg of MK-6069 was prepared in nine steps and 13% overall yield. 

Reduction (s. a. Cleavage, reductive. Elimination, -, Hydrogenation, Lactam reduction, Redox. .., Photoreduction, Ring closure, reductive, Substitution, nucleophilic, -)... 

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