Processes for the preparation of hydroxylated cyclohexyl compounds

A process for the preparation of a compound of Formula I:

• wherein
• both represent either a single bond or a double bond;
• the process comprising:
• (a) protecting a compound of Formula II under conditions to provide a compound of Formula III:
• (b) protecting the compound of Formula III under conditions to provide a compound of Formula IV:
• (c) reacting the compound of Formula IV with a first reducing agent under conditions to provide a compound of Formula V:
• (d) reacting the compound of Formula V with a first oxidizing agent under conditions to provide a compound of Formula VI:
• (e) reacting the compound of Formula VI with an alkene-forming reagent of Formula VII under conditions to provide a compound of Formula VIII:
• wherein the alkene-forming reagent is a Wittig reagent and
• represents a triphenylphosphonium moiety or the alkene-forming reagent is a Horner-Wadsworth-Emmons reagent and
• represents a phosphonate moiety;
• (f) reacting the compound of Formula VIII with a source of singlet oxygen under conditions to provide an endoperoxide of formula IX:
• (g) reacting the endoperoxide of Formula IX with a second reducing agent under conditions to provide a compound of Formula X:
• (h-I) when both in the compound of Formula I are a double bond, protecting the compound of Formula X under conditions to provide a compound of Formula XI(i):
• and
• (i-I) reacting the compound of Formula XI(i) with a second oxidizing agent under conditions to provide the compound of Formula I, or
• (h-II) when both in the compound of Formula I are a single bond, hydrogenating the compound of Formula X under conditions to provide a compound of Formula XIX and protecting the compound of Formula XIX under conditions to provide a compound of Formula XI(ii):
• and
• (i-II) reacting the compound of Formula XI(ii) with a second oxidizing agent under conditions to provide the compound of Formula I;
• wherein
• PG1, PG2 and PG3 are each independently protecting groups, wherein PG1 is a protecting group that is removed by the first reducing agent and each PG2 is the same or different or both PG2 are joined to form a cyclic protecting group;
• R1 is a functional group that is converted into the functional group of a known natural product or a functional analog thereof;
• and
• wherein in the compounds of Formulae I, VII, VIII, IX, X, XI(i), XI(ii) and XIX, one or more available hydrogens in R1 is/are optionally replaced with F and/or one or more of available atoms in R1 is/are optionally replaced with an isotopic label.