Amino acids, reduction using NaBH

Microwave-induced imine formation, subsequent reduction with NaBH(OAc)3 and cyclisation of the resulting amino acid with isothiocyanates was used in an efficient one-pot multi-step synthesis of thiohydantoins (Scheme 4.26). The reductive animation was conducted as a two-step procedure to avoid direct reduction of the aldehyde at high temperatures48. 

R,AR2 O./0 O bap w O rAr2 [273] Reducing agents used LiBH, BH,-py (BAP) NaCNBH, NaBH(OAc), Reductive alkylation works well with aminoesters and a range of anilines. BAP has been found to be the best reducing agent for less stable iminium ion intermediates formed with sec- amines and aldehydes/ketones. Partial racemization of amino acids is sometimes observed. Bfv-alkylation is sometimes observed with aliphatic aldehydes [26] [59] [65] [67] [107] [120] [161] [163] [186] [195] [196] [197] [198] [199] [219] [225] [260] [267-273]... 

Boc-amino acid 472 was attached to 471 using CS2CO3 and KI in DMF to afford 473 (Scheme 9.57). After removal of the Boc group using the TFA/DCM method, treatment with aldehyde 474 and NaBH(OAc)3 in the presence of acetic acid in DCM facilitated the reductive alkylation of the free amine. Resin 475 was then treated with oxoacetic acid derivative 476 and DIC in DCM, forming the key intermediate 477, which was then treated with ammonium acetate 478 and acetic acid in toluene for cyclocleavage to generate the E-and Z-isomers of 479. 

---