Asymmetric Synthesis of Axially Chiral Biaryls via Desymmetrization of 2,2‘,6,6‘-Tetrahydroxybiphenyl Using 1,4-Di-O-benzyl-l-threitol as a Chiral Template

• Published in: Journal of organic chemistry Vol. 65; no. 5; pp. 1335 - 1343
• Main Authors: Tuyet, Tran Mai Thi, Harada, Toshiro, Hashimoto, Kazuyuki, Hatsuda, Masanori, Oku, Akira
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10-03-2000
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo991364g

Sequential etherification of 2,2‘,6,6‘-tetrahydroxybiphenyl (1) with 1,4-di-O-benzyl-l-threitol under Mitsunobu conditions gives desymmetrized biphenyldiol 9 of S-axial chirality exclusively. Cyclization of 9 with 1,ω-dibromoalkanes followed by removal of the chiral auxiliary yields (S)-2,2‘-biphenyldiols 14 with alkylenedioxy bridges at the 6 and 6‘ positions. (S)-6,6‘-Dialkyl- and -diphenyldiols 20 are obtained in an efficient manner via Pd(0)-catalyzed cross-coupling of bis(triflate) derivative 17 with organozinc reagents. Bis(triflate) 17 also serves as an intermediate for asymmetric synthesis of axially chiral biphenyldicarboxylic acid 23, terphenylcarboxylic acid 28, lactone 26, and lactam 30.