Selective synthesis of 2β-functionalizedmethyl penicillin α-sulfoxides 15, which could be important intermediates for conversion of penicillins to cephalosporins, was accomplished as follows. Oxidation of N-nitroso penicillins with m-chloroperbenzoic acid, followed by reductive removal of the nitroso group gave penicillin α-sulfoxides selectively. Thus, 16 was converted to 21 and 19 in the ratio of 5:1, while 23 and 25 were transformed exclusively to α-sulfoxides 24 and 27, in 66% and 50% (from 22) yield respectively. Conversion of 25 to 31 (and thus to cephalothin 2) was achieved via disulfide 29 in 43% yield (AgF) or via 29 and 30 in 20% yield. Similarly, 24 could be transformed to 33, but further conversion to 37 could not be achieved. When 24 was treated with AgClO_4 in dioxane, a ring-expanded product 35 was obtained. 35 has been known as a versatile precursor of cephalosporins. Reaction of 24 with P(OEt)_3 gave 39 in good yield, whose thiazoline ring could be opened and traped as Ag-salt 40 and both 39 and 40 were cyclized to 41. Ozonolysis of 39 gave enol 43 which was converted to 3-hydroxycephem 42.
