Protecting group directed cyclization: asymmetric synthesis of both cis- and trans-dihydrexidine from a common precursor

Published in: Journal, Volume : 69, Issue : 43, Pages : 8994-9000

DOI : 10.1016/j.tet.2013.08.042

Author : Malhotra, Rajesh; Chakrabarti, Sagar; Dey, Tushar K.; Dutta, Swarup; Alapati, Krishna Babu; Dutta, Shantanu; Roy, Subho; Basu, Sourav; Hajra, Saumen

Abstract : Protection group of amino- and tethered o-arene functionality of 1,4-aryl-2-amino-1-butanol derived from l-serine dictates the cyclization mode under acidic conditions leading to reverse diastereoselectivity. N-Boc and acetal protected amino alc. undergo cascade cyclization providing exclusively cis-dihydrexidine via reduction, where formation of C-ring (isoquinoline unit) prior to Friedel-Crafts cyclization control the cis-stereochem. of the B-ring. N-Cbz and O-benzyl protection direct first F-C cyclization yielding the trans-1-aryl-2-aminotetralin and subsequent deprotection-cyclization forming the C-ring afforded dihydrexidine.