Scrambling of the label in a fluorenylphosphonamidic [¹⁸O]-sulfonate during dissociative nucleophilic substitution (elimination–addition): a measure of the importance of preassociation

Abstract

When R(2)CHP(O)(NEt(2))OS(18)O(2)Ar (R(2)CH = 9-fluorenyl, Ar = p-tolyl) undergoes nucleophilic substitution (elimination-addition) with Et(2)NH (0.4 mol dm(-3) in CHCl(3)) the phosphene intermediate R(2)C=P(O)NEt(2) recombines with the sulfonate leaving group (internal return), causing scrambling of the (18)O label, more quickly than it diffuses away; efficient conversion into R(2)CHP(O)(NEt(2))(2) therefore depends on preassociation between the substrate and the nucleophile.

Mechanistic Studies on a Sulfoxide Transfer Reaction Mediated by Diphenyl Sulfoxide/Triflic Anhydride

“…Half of the Tf 2 O would react initially with [ 18 O]-5 , and the other half with [ 16 O]-15 to produce triflyloxysulfonium ions 6 a that are partially labelled (i.e., 92 %÷2=46 % 18 O) and unlabelled triflate anions. Triflate exchange would scramble all 12 oxygen atoms in the triflyloxy and triflate groups further reducing the labelling in ions 6 a 24. Therefore, for a 1:1:2 mixture of [ 18 O]-5 , [ 16 O]-15 and Tf 2 O undergoing triflate-mediated 18 O-exchange, the theoretical 18 O-enrichment in product sulfoxides 5 and 15 should be less than 8 % (i.e., 92 % 18 O÷12 oxygen atoms=7.7 %).…”

“…Furthermore, by reversing the order of addition of sulfoxides 2- R and [ 18 O]-5 , 18 O-enrichment close to the theoretical maximum was achieved for the equatorial isomer. Incorporation of 18 O with such high efficiency can only arise through the formation of oxygen-bridged disulfonium ion 26 (Scheme 8 c) as any other mechanism (e.g., 18 O transfer via triflate exchange) would result in significant dilution of the label 24…”

Reaction mechanisms : Part (iii) Polar reactions

“…Efficient conversion into 95 (X = NEt 2 ) therefore depends on pre-association between the substrate and the nucleophile. 76 The anhydride 95 (X = OTs) has been found to be more reactive than the corresponding chloride 95 (X = Cl) and also contains an alternative site, the S atom, at which the nucleophile can attack. 77…”

“…76 The anhydride 95 (X = OTs) has been found to be more reactive than the corresponding chloride 95 (X = Cl) and also contains an alternative site, the S atom, at which the nucleophile can attack. 77…”