Thionocarbonates, Corey-Winter olefin

The Corey-Winter olefin synthesis is based on the stereospecific loss of carbon dioxide or carbon disulfide from the carbenes formed by treatment with bivalent organophosphorus compounds of thionocarbonates or trithiocarbonates [218-220]. 

Corey-Winter olefin synthesis. The Corey-Winter olefin synthesis (1, 1233-1234) involves treatment of a thionocarbonate with trimethyl phosphite ... 

Corey-Winter olefin synthesis (1, 1233-1234). Chong and Wiseman1 were able to demonstrate the transient existence of bicyclo[3.2.1]octene-l (2, a bridgehead alkene which violates Bredt s rule) by application of the Corey-Winter olefin synthesis. Thus treatment of the thionocarbonate (1) with triethyl phosphite at reflux (165°) for 24 hr. in the presence of 1,3-diphenylisobenzofurane (1, 342-343 2, 178-179) leads to the formation of two Diels-Alder adducts (3) and (4) derived from (2). 

The Corey-Winter olefin synthesis is a two-step transformation of a diol 1 to an olefin 3.1"3 A cyclic thionocarbonate 2 is prepared from the diol 1, and subsequent heating of 2 with phosphite affords olefin 3. 

However, evidence opposing the intermediacy of a carbene species in the Corey-Winter olefin synthesis also exists.3 Thermal decomposition of hydrazone salt 14, which is proposed to proceed via carbene 12, leads to a mixture of products 13, 15, and 16.7 Thus, an alternative mechanism has been proposed for the Corey-Winter reaction that invokes a phosphorus ylide. In this mechanistic scenario, initial reaction of thionocarbonate 10 with trimethylphosphite affords zwitterion 11. Cyclization generates... 

The Corey-Winter olefination was used on kilogram scale in the synthesis of 2, 3 -dideoxyadenosine (39).17 Exposure of diol 36 to thiophosgene gave thionocarbonate 37 in 92.5% yield, and subsequent treatment of 37 with P(OMe)3 generated olefin 38 in 60.5% yield. Olefin 38 was then converted in two steps and 56% yield to 2, 3 -dideoxyadenosine 39. Remarkably, the adenosine amino substituent did not require protection during this synthetic sequence. Overall, 905 g of 39 was prepared via this route. 

The Corey-Winter olefin synthesis has been performed on p-lactam derivatives.18 This olefination was employed in cases where traditional Wittig-type olefination of the corresponding aldehyde led to disappointing results. In one example, treatment of 40 with carbonyldiimidazole and exposure of the resulting thionocarbonate to P(OMe)3 afforded olefin 41 in 81% yield. 

Finally, Paterson and Schlapbach employed the Corey-Winter olefination to generate a trisubstituted olefin in their studies toward a total synthesis of discodermolide.19 In this example, diols 42 and 43 were treated with thiocarbonyldi-imidazole to give the corresponding thionocarbonates. Exposure of this mixture of thionocarbonates to phospholidine 21 at 50 °C generated olefin 44 in 81% yield. 

Corey-Winter olefin synthesis (1, 1233-1234 2,439-441 3,315-316 4, 269-270, 541-542 5,34, 661). Vedejs and Wu converted thionocarbonates into olefins by alkylation with methyl iodide (90°, DME, sealed tube) followed by reduction (zinc dust—ethanol or magnesium amalgam—THF). This two-step procedure was used for preparation of the cyclobutene (2) in this case the reaction with triethyl phosphite was immeasurably slow. 

By application of the Corey-Winter reaction,vicinal diols 1 can be converted into olefins 3. The key step is the cleavage of cyclic thionocarbonates 2 (1,3-dioxolanyl-2-thiones) upon treatment with trivalent phosphorus compounds. The required cyclic thionocarbonate 2 can be prepared from a 1,2-diol 1 and thio-phosgene 4 in the presence of 4-dimethylaminopyridine (DMtVP) ... 

Cyclic thionocarbonates (41) can be cleaved to olefins (the Corey-Winter reaction)274 by heating with trimethyl phosphite275 or other trivalent phosphorus compounds276 or by treatment with bis(l,5-cyclooctadiene)nickeI.277 The thionocarbonates can be prepared by treatment of 1,2-diols with thiophosgene and 4-dimethyIaminopyridine (DMAP) 278... 

There have been several modifications to the Corey-Winter reaction, the most significant of which was published by the Corey group in 1982.9 Corey and Hopkins reported that by using a diazaphospholidine in place of trimethylphosphite, thionocarbonates could be converted to the corresponding olefins at significantly lower temperatures. Thus, thionocarbonate 20 was prepared from diol 19 in 93% yield, and subsequent treatment of 20 with diazaphospholidine 21 afforded olefin 22 in 88% yield. Several complex examples were disclosed in which olefins were generated in 70-94% yield.9... 

The Corey-Winter reaction has also been used in a formal synthesis of the AIDS drug (-)-abacavir (35).16 Thionocarbonate 33 was prepared from diol 32 in 78% yield. Then, treatment of 33 with phospholidine 21 afforded olefin 34 in 65% yield. The preparation of 34 constitutes a formal synthesis of (-)-abacavir (35). 

The final twistane synthesis we will consider originates from the one-bond disconnection indicated by Path D in Unnatural Products-1. Just as with Path A, the synthesis uses a Diels-Alder reaction to establish the bicyclo[2.2.2]octane substructure of key intermediate 9. The cycloaddition of cyclohexadiene 43 and methyl propiolate afforded a mixture of regioiso-meric cycloadducts 44 and 45. Catalytic hydrogenation of the mixture occured from the sterically most accessible face of the olefin to afford meso-compound 46 and its diastereomer 9. Diester 9 was subjected to an acyloin condensation, and catalytic hydrogenation of the resulting a-hydroxyketone gave diol 47. A Corey-Winter reaction was used to convert 47 to 49 via thionocarbonate 48. Catalytic hydrogenation completed the synthesis. 

Corey-Winter elimination dibenzobarralene (442). In a similar way, spirohex-4-ene was obtained in 80% yield from (443). Daub and his co-workers have synthesized several uncommon olefins, among these (442), from parent cyclic thionocarbonates, using iron pentacarbonyl as the efficient elimination promoter. Semmelhack and Stauffer have reported that bis-(cyclo-octa-l,5-diene)nickel (444) converts thionocarbonates of vic-diols into the corresponding olefins in excellent yields and with a high degree of stereospecificity. In connection with a discussion of the mechanistic pathways of this reaction, the authors presented evidence for the intermediacy of the carbene complex (445). 

Olefin synthesis. Corey and Winter" devised a novel olefin synthesis from 1,2-diols utilizing in the first step the reaction with thiocarbonyldiimidazole (2), a reagent prepared from 2 moles of imidazole and 1 mole of thiophosgene. Corey postulated that treatment of the cyclic thionocarbonate (3) with a reagent which would abstract sulfur to form the curbenc (4) would effect cis elimination to the olefin and found that trimethyl phosphite effects this reaction cleanly and in high yield. [Pg.1350]

In 1963, Corey and Winter disclosed their discovery of a new method for the stereospecific synthesis of olefins from 1,2-diols. Treatment of mejo-hydrobenzoin 4 with carbonyldiimidazole in toluene at reflux gave the corresponding cyclic thionocarbonate 5 with quantitative conversion. Exposure of 5 to trimethylphosphite then afforded cis-stilbene 6 in 92% yield. fraHJ-Stilbene could be obtained by starting with the corresponding tram-diol. This two-step reaction sequence could also be used for the synthesis of cyclic olefins. Treatment of rraiw-cyclodecanediol 7 with... 

---