Process for the preparation of lubiprostone

A process for the synthesis of lubiprostone comprising:

• a) coupling of cyclopentenone of formula I:
• with an organocopper compound of formula III:
• to provide a compound of formula IV:
• b) reacting the compound of formula IV with hydrogen in the presence of a catalyst to provide a compound of formula V:
• c) oxidising the compound of formula V to provide a compound of formula VI:
• d) converting the compound of formula VI to lubiprostone via 1) hydrolysis followed by desilylation or 2) desilylation followed by hydrolysis,
• wherein R1, R2, R3 and Si together form a silyl protecting group,
• R13 is nothing, Li(CN), Li2(CN)Me, Li2(CN)2-thienyl, Li(CH═CHCH(OR17)CF2CHnCHmCHoCH3), or
• Li2(CN)(CH═CHCH(OR17)CF2CHnCHmCHoCH3),
• each of n,m and o is 1 or 2 such that either C17 through to C19 is fully saturated or C17 through to C19 contains one single and one double or triple bond,
• R16 is a substituted or unsubstituted benzyl protecting group, and
• R17 is a substituted or unsubstituted benzyl protecting group.