Reaction of Cyclic Phosphoramidites with Disulfides. I. A Novel Synthesis of Phosphoramidothioates

Abstract

amount of water present) during the titration. Therefore, all titrations were carried out at 0.005 M concentrations. The pKa point was always in the desired flat portion of the titration curve. The e.m.f. at half neutralization was taken as one-half the calculated stoichiometric end point. As mentioned above, the latter was always very close to the observed inflection point, and resulted in a maximum error of e.m.f. values of about 5 mv. Runs were carried out in duplicate. Repeat determinations were always within 10 mv. and generally within 5 mv.The collected Ae.m.f. values at half neutralization ( values, referred to N,N'-diphenylguanidine) are given in Table III. A plot of these values vs. literature pKj(H:0) values for several of these bases (diphenylguanidine, triethylamine, pyridine, acetamide, and urea) indicated a straight-line relationship, and so the p/Guno) values for the series of N,N-disubstituted amides are interpolated from this line (Tables I and III).The least-squares calculation of pifa(H¡o) vs. was pATa(HiO) = 10.10 -0.0118 , with a standard deviation of 33 mv.

Reaction of disulphides with cyclic phosphoramidites

“…Although the reaction between diallyldisulphide and cyclic phosphoramidites was assumed to involve an SNi' mechanism this was not proven in the original study. 2 We have found that dibut-2-enyl disulphide is desulphurated to but-2-enyl-I-methylallyl monosulphide by 2-diethylamino-l,3,2-dioxaphospholane and 2-diethylamino-4methyl-l,3,2-dioxaphospholane, thus confirming the original hypothesis.…”

Allylic Disulfide Rearrangement and Desulfurization: Mild, Electrophile-Free Thioether Formation from Thiols

“…As first described by Baldwin,2a allylic disulfides are in equilibrium with allylic thiosulfoxides by virtue of a [2,3]-sigmatropic rearrangement of undetermined stereoselectivity (Scheme 2) . The equilibrium, which strongly favors the allylic disulfide, can be displaced toward the formation of an allylic sulfide by the addition of a thiophilic agent.…”

“…The equilibrium, which strongly favors the allylic disulfide, can be displaced toward the formation of an allylic sulfide by the addition of a thiophilic agent. At 60 °C in benzene, rate constants for the rearrangement with transfer of sulfur to triphenylphosphine were found to be strongly dependent on the substitution pattern 2a. Whereas the desulfurative rearrangement was reported to be slow for primary allylic disulfides (R 1 ,R 2 = H and R 3 ,R 4 = H/alkyl; k = 0.7 × 10 -4 to 8.6 10 -4 s -1 ), a significant rate acceleration was observed with secondary and tertiary allylic disulfides (R 1 ,R 2 = alkyl and R 3 ,R 4 = H; k = 1.4 × 10 -2 to 1.9 10 -2 s -1 ) 2a.…”

“…At 60 °C in benzene, rate constants for the rearrangement with transfer of sulfur to triphenylphosphine were found to be strongly dependent on the substitution pattern 2a. Whereas the desulfurative rearrangement was reported to be slow for primary allylic disulfides (R 1 ,R 2 = H and R 3 ,R 4 = H/alkyl; k = 0.7 × 10 -4 to 8.6 10 -4 s -1 ), a significant rate acceleration was observed with secondary and tertiary allylic disulfides (R 1 ,R 2 = alkyl and R 3 ,R 4 = H; k = 1.4 × 10 -2 to 1.9 10 -2 s -1 ) 2a. On the basis of early observations, 2a,e we reasoned that use of polar solvents to stabilize the polar thiosulfoxide intermediate would enable the reaction to be conducted at room temperature, thereby providing a mild and selective functionalization method for thiols, complementary to the allylic selenosulfide methodology.…”

Dechalcogenative Allylic Selenosulfide and Disulfide Rearrangements: Complementary Methods for the Formation of Allylic Sulfides in the Absence of Electrophiles. Scope, Limitations, and Application to the Functionalization of Unprotected Peptides in Aqueous Media.

“…The phosphine-promoted desulfurative allylic rearrangement of diallyl disulfides to give allyl sulfides [53][54][55][56][57] proceeds by way of a [2,3]-sigmatropic rearrangement via a diallyl thiosulfoxide intermediate 58,59 and, thus, is closely related to the well known Evans-Mislow rearrangement of allylic sulfoxides. 60 This dechalcogenative rearrangement, which may also be induced to operate in the reverse direction on treatment of allyl sulfides with elemental sulfur, 61 and which is potentially important in the chemistry of essential oils derived from garlic, 62 appeared to us to hold promise as a means of rendering disulfides permanent if it could be caused to function at ambient temperatures in protic solvents.…”