Triethylsilane lactam reduction with

Reactions.—A-Alkylation of acetanilides has been achieved using a two-phase system of water and benzene with sodium hydroxide as base and triethylbenzylam-monium chloride yields are better than 80%. An efficient two-step process for the A-methylation of unsubstituted amides, lactams, and ureas has been described which involves initial formation of the corresponding methylol, by treatment with formaldehyde, followed by reduction with either triethylsilane and trifluoroacetic acid or with hydrogen over palladium in TFA. A method for the methylthiomethy-lation of both amides and lactanes has appeared. ... 

Alternatively, the imide-acid chloride is reacted with methanol to give the imide ester which, after borohydride reduction and triethylsilane/trifluoroacetic acid treatment, furnishes the bicyclic lactam 6 as a racemate. The latter is acylated with either propanoyl chloride or 3-phcnylpropanoyl chloride and the resulting amides 7 deprotonated and alkylated with (bro-momethyljbenzene or iodomethane, respectively, to give the major alkylation products 8 with d.r. >98 2 and in 65% yield3. 

McMurray [151] has described the acid-assisted cleavage of the N]-C4 bond in trans 4-hydroxyphenyl p-lactams. The ring opening reaction may proceed with concomitant reduction or formation of carbon-carbon coupling products, as a function of the reagent employed. For instance, Scheme 60, treatment of 196 with 4 equivalents of triethylsilane in neat trifluoroacetic acid led to compound 197. On the contrary, treatment with anisole in trifluoroacetic acid led to compound 198. Unfortunately, no data are provided by authors regarding process yield or final diastereomeric ratio. 

Reduction of 2 with triethylsilane catalyzed by TiCU effects only cleavage of the C-O bond to give 5 in >94% de. This product is reduced to the lactam 6 by Li/NH. Unfortunately the chiral auxiliary is not recovered. 

The reductive cyclization of N-(w-iodoalkyl)succinimides induced by samarium(II) iodide was disclosed by Ha et al. as a novel method for making pyrrolizidines and indoUzidines (Scheme 46). " In the apphcation of the method to the synthesis of (+)-lentiginosine (127), reaction of N-(4-iodo-butyl)tartarimide (+)-335 with samarium(II) iodide in the presence of the iron(III)—tris(dibenzoylmethane) complex as catalyst produced the unsaturated indolizidin-3-one (+)-336 in 82% yield. Reduction of the bridgehead alkene was accomplished with triethylsilane and trifluoroacetic acid via an intermediate acyliminium ion, giving (+)-337 as the sole product in 93% yield. Routine hydrolysis of the silyl ethers produced the known diol (+)-177, after which reduction of the lactam with Hthium aluminum hydride then completed this short synthesis of (+)-127. 

---