Coupling-desulfurization scheme

Figure 5. Schematic of a coupling—desulfurization scheme. (Reproduced with permission from Reference 55. Copyright 1986 Pergamon Press, Inc.)...

Methyl fluoro(diethoxyphosphono)dithioacetate (34) has been prepared from difluorinated precursors [56], Fluorophosphonothioacetamides (35) derived from this dithioester, have been successfully transformed into highly functionalized fluoroalkenes (36). Judicious selection of the aldehyde coupling partner can lead expeditiously to the preparation of fluoroolefin dipeptide isosteres following elaboration of the carboethoxy group and desulfurization (Scheme 11). 

Scheme 7.44. Sml2-promoted domino reductive desulfuration/reductive coupling process of lactams 7-166 with an aldehyde.

Interestingly, treatment of diene 215a with methanesulfonic acid afforded 216 as a single diastereomer in 88% yield, the structure of which was confirmed by X-ray analysis (Scheme 60). The transformation of 216 into 217 started with an alkylation, followed by reductive desulfurization and triazene formation to afford compound 217 in 92% yield. Upon treatment with diiodomethane, triazene 217 was smoothly converted to aryl iodide 218 in 75% yield. Pd-catalyzed intramolecular Heck coupling of 218 led to the desired product 219b in 62% yield. 

Kappe has recently published a modified desulfurative cross-coupling method, using a direct reaction on thioamides under microwave assistance.123,124 It was shown that, in contrast to cross-coupling alkylsulfanyl-iV-heteroaromatics and boronic acids, 2 to 3 equivalents of CuTc cofactor were needed to achieve high yielding conversions (Scheme 64). 

Thiane oxides have been shown to be reduced cleanly back to the thiane with phosphorus pentasulfide under conditions to which sulfones, sulfinates, ketones, esters and amides are inert (78CJC1423) the potential of this reaction, though not yet applied, is obviously considerable, especially when coupled with the old-established Raney nickel desulfurization technique. Thiane itself is desulfurized to pentane (with traces of cyclopentane) but the opportunity to construct alkyl chains of great complexity regio- and stereo-specifically is there. At the very least, the reduction to tetrahydrothiopyrans presents a very useful entree into a wide range of 2-substituted thianes (Scheme 2). 

The exocyclic C(2)-S bond of a 2-thiopenem 50 can undergo radical reactions. As depicted in Scheme 28, its desulfurative stannylation reaction with azobis(isobutyronitrile) (AIBN) and tributyltin hydride leads to a penem stannane 51 <1995TL775>. The latter allows subsequent palladium(0)-mediated cross-coupling reactions with... 

The chirality present at the sulfur atom of, for example, p-tolylsulfinyl carbanion leads to the formation of a diastereoisomeric mixture of y-hydroxy sulfoxides on reaction with prochiral epoxides (Scheme 87). This reaction, coupled with the efficient desulfurization of the resulting sulfoxide by Raney nickel, has been used ingeniously for the enantioselective synthesis of rra j-2-methylcyclohexanol from epoxycyclohexane and (H-)-p-tolylsulfinylmethyllithium (Scheme 87). 

Excellent results have again been reported for the condensation of allyl bromides or chlorides with l-phenylthio-2-alkenyllithiums. These "soft" nucleophiles are readily generated by the treatment of suitable 2-alkenyl phenyl sulfides with the -butyllithium/DABCO complex (DABCO = l,8-diazabicyclo[2.2.2]octane). The "tail-to-tail" connected products can be desulfurized without double bond shift as demonstrated by the synthesis of a/Z-fE -squalene (123 Scheme 1-88) and a (Z,E,E,E)-isomer thereof as well. Similar allyl-allyl couplings have also been executed using metalated allylic sulfones rather than sulfides. ... 

Silverstein et al. (51, 136) began their synthesis of racemic ipsenol by coupling 2-bromomethyl butadiene (237) with the anion of the dithiane derivative (236) of 3-methyIbutanal (235) (Scheme 47). Desulfurization of (238) and reduction of ketodiene (239) gave the desired alcohol (240). 

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