Enol sulfonates steroids

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

It was found that the counteranion of the 1-fluoropyridinium salts considerably affects selective fluorinations.54 For example, fluorination with 1-fluoropyridinium triflate (la) was compared to that with l-fluoro-4-methylpyridinium-2-sulfonate (2b) using a steroid 10 containing an acetoxy function and a conjugated trimethylsilyl enol ether as the substrate.54... 

In contrast, Michael additions of a,a-disubstituted lithium enolates proceed, apparently via the chelated form of enone sulfoxides (Figure 5.2), with almost complete jt-facial diastereoselectivity [104]. This methodology has been used in the asymmetric synthesis of the pheromone, (-)-methyl jasmonate (121), from cyclopentenone sulfoxide (98b) [105] via the intermediate (120), which was formed in at least 98% enantiomeric purity upon asymmetric Michael addition of bis a-silylated a-lithioacetate to (98b). Addition of the a-bromo enolate (122) to enantiomerically pure (98a) and oxidation gives the product sulfone (123), with almost complete asymmetric -induction with respect to the sulfoxide. Sulfone (123) was then converted into the steroidal sex hormone, (+)-oestradiol (124) (Scheme 5.42) [106]. 

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