Winter Olefination

The exact mechanism of the reaction between the thionocarbonate and the trialkylphosphite is not known. There are two possible pathways (I and II) and both of them are presented. In pathway I, the formation of an ylide intermediate is postulated based on inhibition studies, while in pathway II the generation of a carbenoid intermediate is assumed. There is direct experimental evidence that the elimination of the cyclic 1,2-thionocarbonate involves the formation of a carbenoid intermediate.  

The enantiospecific synthesis of naturally occurring cyclohexane epoxides such as (+)-crotepoxide and (+)-boesenoxide was accomplished by T.K.M. Shing et al. The key Intermediate 1,3-cyclohexadlene was prepared using the Corey-Winter protocol on a c/s-vicinal diol. The resulting diene was then converted to the natural product after several steps. 

The absolute configuration of radiosumin, a novel potent trypsin inhibitory dipeptide, was determined by T. Shioiri and co-workers by carrying out the first enantioselective total synthesis of the natural product. The s-trans 1,3-diene in one of the key synthetic intermediates was installed by the Corey-Winter olefination using the Corey-Hopkins reagent (1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine). 

In the laboratory of J.H. Rigby, synthetic studies were undertaken on the ingenane diterpenes. During these studies, it was necessary to investigate the ring opening reactions of a structurally complex allylic epoxide intermediate. This allylic epoxide was prepared from a 1,3-diene in three steps dihydroxylation, epoxidation and Corey-Winter olefination. 

Fleet and co-workers synthesized L-(+)-swainsonine and other more highly oxygenated monocyclic structures that exhibited inhibitory activity toward naringinase (L-rhamnosidase). In order to remove a c/s-vicinal diol moiety in the endgame of the synthesis, the Corey-Winter olefination was utilized. 

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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 thionocarbonale with trimethyl phosphite ... 

Corey-Winter olefin synthesis (I. I23.3-I234). Chong and Wiseman were able to demonstrate the transient existence of bicyclo[3.2.l]octenc-l (2, a bridgehead alkene which violates Bredt s rule) by application of the Corey-Winter olefin synthesis. Thus treatment of the thionocarbonatc (I) with triethyl phosphite at reflux (165°) fur 24 hr. in the presence of I,3-diphenyli obenzofurane (1, 342-343 2, 178-179) leads to the formation of two Diels-Alder adducts (3) and (4) derived from (2). 

P-Elimination of a hetero-substituted C-C single bond. The best-known reactions of this type are the heteroatom -heteroatom (Het -Het ) elimination (Het = O, Hal, S,...), heteroatom -hydrogen (Het -H ) elimination, Peterson olefination, Tschugajew reaction and Corey-Winter olefination. 

Corey-Winter olefin synthesis. Synthesis of olefins from 1,2-diols and thiocarbonyldiimidazole. Treatment of the intermediate cychc thionocarbo-nate with trimethylphosphite yields the olefin by els elimination. 

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. 

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