Patent ID: 8653282

Claim:
A method for preparing intermediates of formula 6 comprising the steps of: a. reacting reagents of the formulas HS—CH 2 —CO 2 R a and CHR 5 ═CR 4 —CO 2 R a to obtain an intermediate of formula 7: b. cyclizing the intermediate of formula 7 in a solvent and in the presence of TiCl 3 (OiPr) or a chiral variant of TiCl 3 (OiPr) selected from the group consisting of 1,1′-bi-2-naphthol (BINOL), a substituted BINOL, a chiral diol, 1,1′-binaphthalene-(2,2′-diyl)bis(diphenylphosphine) (BINAP), a compound substituted with 2,5-alkyl-substituted phospholane rings (a DuPhos compound), α,α,α′,α′-tetraaryl-1,3-dioxolan-4,5-dimethanol (Taddol), and a tartrate, and in the presence of an amine base to obtain the intermediate of formula 6, wherein: R 4 and R 5 are each independently H, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 6-10 -aryl, C 6-10 -aryl-C 1-6 -alkylene, C 1-5 -heteroaryl-C 1-6 -alkylene, C 3-10 heterocycle, C 5-10 -heteroaryl, —O—C 1-6 -alkyl, —O—C 6-10 -aryl, —O—C 3-10 heterocycle, —O—C 5-10 -heteroaryl, —NR′R″, fluoro, C 1-6 -fluoroalkyl, or C 1-6 -fluoroalkoxy, and wherein R′ and R″ are each independently H or C 1-6 -alkyl, and wherein each group is optionally substituted by one or more groups selected from OH, oxo, halogen, C 1-6 -alkyl, and O—C 1-6 -alkyl; and R a is C 1-10 -alkyl.