Lactams reduction with borane

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>. 

Methylcryptaustoline iodide (14) was synthesized from phenylacetic acid 47 by Elliott (39) as shown in Scheme 7. Nitration of 47 to the 6-nitro compound 48 and reduction with sodium borohydride afforded lactone 49. Reduction of the aromatic nitro group with iron powder in acetic acid gave ami-nolactone 50, which was converted to tetracyclic lactam 51 with trifluoroacetic acid in dichloromethane. Reduction of the lactam by a borane-THF complex followed by treatment with methyl iodide afforded ( )-0-methylcryptaustoline iodide (14). 

Tetrahydrothiazin-3-ones are lactams that have been reduced to tetrahydrothiazines with borane <1980JHC449>, sodium borohydride <1992JOC4215>, or LAH <1987H(26)1503>, without cleavage of carbon-sulfur bond. In one case, incomplete reduction occured with LAH the intermediate lactol was dehydrated to give a dihydrothiazine as main product <1989JPS937>. 

In this presentation, reductive a-allylation of indoles and reductive diallylation of lactams with allylic boranes as well as a new way to isoquinuclidine structures are described. 

With 51 in hand, hydrogenation under acidic conditions was readily achieved in alcoholic solvents to form 28, which was cyclized under basic conditions to give lactam 29. Finally, conversion of lactam 29 to the desired benzazepine 6 was accomplished by borane reduction (generated in situ) to form benzazepine 6, isolated as the tosylate salt in 81% yield. The reduction could also be accomplished with lithium aluminum hydride. This route was efficient and robust, as it uses... 

Reduction of lactams Tertiary lactams are transformed into tertiary amines. 9-BBN holds an advantage over borane because it does not complex with amines and therefore no excess reagent is required. 

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