Patent ID: 6875877

Claim:
A method of preparing an enantiomerically-enriched tetrahydrobenzothiepine-1-oxide having the formula (I): wherein: R 1 and R 2 are independently selected from the group consisting of H, alkyl, alkenyl, and alkynl; R 3 is selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, and cycloalkyl; wherein aryl can be substituted with one or more substituent groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, polyalkyl, and OR 19 ; R 19 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, polyalkyl and, alkylarylalkyl; R 19 is optionally substituted with quaternary heterocycle; R 4 , R 5 , R 6 , R 7 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, halo and —NR 9 R 10 ; R 9 and R 10 are independently selected from the group consisting of H, and alkyl; R 3 and the hydroxyl at the 4-position of the enantiomerically-enriched tetrahydrobenzothiepine-1-oxide are in a syn-conformation with respect to each other; and the sulfur at the 1-position of the seven-member ring and the carbons at the 4-position and the 5-position of the seven member ring are chiral centers; wherein the method comprises cyclizing an enantiomerically-enriched aryl-3-propanalsulfoxide having the formula (II): wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as described above, and wherein the sulfur is an enantiomerically-enriched chiral center, to form the enantiomerically-enriched tetrahydrobenzothiepine-1-oxide of formula (I).