Practical stereoselective synthesis of (2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)acetic acid

✍ Scribed by Tomoichi Shinohara; Kazumi Kondo; Hidenori Ogawa; Toyoki Mori; Kyoko Nozaki; Tamejiro Hiyama

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 134 KB
• Volume: 12
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(2000)12:5/6<425::aid-chir23>3.0.co;2-e

✦ Synopsis

Highly enantioselective asymmetric hydrogenation of readily accessible olefins, (E)- and (Z)-[1-(toluene-4-sulfonyl)-1,2,3, 4-tetrahydro-1H-benzo[b]azepin-5-ylidene]acetic acid (4a and 4b, respectively) and [1-(toluene-4-sulfonyl)-2, 3-dihydro-1H-benzo[b]azepin-5-yl]acetic acid (4c), is presented as an efficient and straightforward route to (R)-[1-(toluene-4-sulfonyl)-2,3,4, 5-tetrahydro-1H-benzo[b]azepin-5-yl]acetic acid [(R)-1] which is a key intermediate for the synthesis of non-peptide AVP V2-agonist. Hydrogenation of carboxylic acid 4c gave (R)-1 in quantitative yield and 85% ee using Ru(OAc)2[(S)-H8-BINAP], a Ru(II) complex of a partially hydrogenated BINAP (H8-BINAP), as a catalyst. When (R)-1 of 76% ee was transformed into the corresponding isopropylamide 6, pure enantiomer (R)-6 was obtained in 75% yield by recrystallization from MeOH.