Olefination Corey-Winter olefin synthesis

The preparation of 4-alkenyl (3-lactams (II, Fig. 9) has been reported through either Homer-type olefination of a common 4-formyl (3-lactam or the Corey-Winter alkene synthesis applied to 4-dihydroxyalkyl (3-lactams [263]. 

As expected, the yields of catenanes by this approach are low, which is why improved methods for the preparation of such compounds have been developed. The acyloins are often only intermediate products in a multistep synthesis. For example they can be further transformed into olefins by application of the Corey-Winter fragmentation. 

The Corey-Winter reaction provides a useful method for the preparation of olefins that are not accessible by other routes. For instance it may be used for the synthesis of sterically crowded targets, since the initial attack of phosphorus at the sulfur takes place quite distantly from sterically demanding groups that might be present in the substrate molecule. Moreover the required vicinal diols are easily accessible, e.g. by the carbon-carbon bond forming acyloin ester condensation followed by a reductive step. By such a route the twistene 10 has been synthesized ... 

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). 

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). 

G.W.J. 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. 

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]

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 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 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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