What is Corey-Winter reaction?
The Corey-Winter reaction is the reaction of a vicinal diol with 1,1-thiocarbonyldiimidazole to form a thiocarbonate, which is then converted to the corresponding olefin by cis-reduction heat elimination promoted by phosphite. The improved method uses thiophosgene to reduce the reaction temperature a lot, and the mild conditions can also be applied to complex molecules with multiple functional groups. The trithiocarbonate generated by non-vicinal diols also completes the elimination smoothly.
Features
- One of the features of this reaction is that it can stereospecifically synthesize various substituted olefins. For example, meso-(exo-)racemic benzoin can give cis-stilbene / trans-stilbene under standard conditions. Since there are a large number of methods for synthesizing vicinal diols with defined stereochemistry, the Corey-Winter reaction can be used in conjunction with the Corey-Winter reaction to achieve the mutual conversion of cis-(trans-)olefins.
- Another feature of this reaction is that it can synthesize high-strain olefins in high yields. For example, trans-cyclooctane (heptane) has been synthesized by this method. Of course, these molecules are unstable and need to be captured by conjugated dienes. In addition, extremely strained tetrasubstituted bridgehead olefins have also been synthesized.
Fig 1. Corey-Winter reaction and its mechanism. [1]
Mechanism of Corey-Winter Reaction
- The first step of the reaction mechanism is the nucleophilic addition of alcoholic hydroxyl group to thiocarbonyl group. The intermediate generated eliminates one molecule of HCl or imidazole. The above process is repeated to obtain a stable thiocarbonate.
- Then the intermediate added with phosphite is thermally decomposed into carbene (Ⅰ) and releases thiophosphite. There is direct experimental evidence that Ⅰ can participate in the intramolecular insertion reaction.
- The generated carbene reacts with the second molecule of phosphite to obtain ylide Ⅱ. Indirect evidence comes from the ylide generated by the corresponding trithiocarbonate can be captured by aldehyde to obtain ketene thioacetal.
- Ⅱ undergoes concerted ring elimination to produce stereochemically determined olefins, while releasing carbon dioxide and phosphite.
Application Examples of Corey-Winter Reaction
- Example 1: Using Corey-Winter reaction to introduce conjugated double bonds, the total synthesis of ottelione A/B was successfully achieved. [2]
- Example 2: In the last step of the synthesis of the Stemona alkaloid (iso)didehydrostemofoline, this reaction was also used to obtain separable diastereoisomeric thiocarbonates, which were successfully synthesized by elimination reactions to fully demonstrate the mildness of the Corey-Winter reaction conditions. [3]
- Example 3: Recently, an electrochemical version of the Corey-Winter reaction was developed to achieve the synthesis of natural α-pyrone in high yield and high stereoselectivity in a methanol-water medium [MeOH/H2O (80:20)]. [4]
Fig 2. Synthetic examples via Corey-Winter reaction.
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References
- Corey, E. J., and Roland AE Winter. J. Am. Chem. Soc. 1963, 85(17), 2677-2678.
- Araki, Hiroshi, et al. Organic Letters, 2003, 5(21), 3903-3906.
- Brüggemann, Markus, et al. J. Am. Chem. Soc., 2003, 125(50), 15284-15285.
- López-López, Ernesto Emmanuel, et al. Beilstein Journal of Organic Chemistry, 2018, 14(1), 547-552.
