Stetter reaction pdf

The requisite vinylphosphonates of type 6 were prepared by treatment of the corresponding aldehyde 5 with a preformed bis-phosphonate complex, as demonstrated by Ojea and Ruiz Scheme 2. With a series of vinylphosphine oxides and vinylphosphonates prepared, we were able to test our hypothesis on the viability of these Michael acceptors for the intramolecular Stetter reaction.

Structures with an aromatic backbone employing a vinylphosphine oxide or vinylphosphonate as the electrophilic acceptor afford the Stetter product in typically high yields and enantioselectivities Table 1. Vinylphosphine oxide 4a provides higher yields than its vinylphosphonate congener 8 while enantioselectivities are increased as well entries 1 and 9. The presence of halogen substituents on the aromatic ring entries 2—4 is well tolerated as long as reaction time is limited to 30 minutes.

Electron donating p -methoxy aldehyde 4e shows only a slight increase in selectivity over sigma withdrawing m -methoxy aldehyde 4d and only a slight decrease in chemical yield.

Five membered carbocycle 7g was also obtained in excellent yield and high enantioselectivity. Previously, we demonstrated that aliphatic aldehydes are competent substrates to undergo the intramolecular Stetter reaction. Phosphonate 11a was obtained in modest yield and enantioselectivity.

Gratifyingly, when the diethyl vinylphosphonate was switched to the diphenyl phosphonate 10b , the yield and enantioselectivity of the desired product 11b were both improved substantially entry 2. This increase in ee is most likely due to the increased steric demand of the diaryloxy group, but indicates that tuning of selectivities is possible using this approach.

Introduction of an oxygen in the aliphatic chain 10c gives higher yields and enantioselectivities in the Stetter product 11c compared to its alkyl congener 11a entry 3 vs entry 1. It is also possible to form a carbocycle bearing a phosphine oxide moiety 11d which proceeds in good yield and enantioselectivity. In summary, we have developed an intramolecular Stetter reaction employing vinylphosphine oxides and vinylphosphonates as electrophilic acceptors. Both aromatic and aliphatic substrates are tolerated providing keto phosphonates and phosphine oxides in good to excellent yields and enantioselectivities.

This extension of the Stetter reaction leads to interesting new enantioenriched scaffolds of phosphorus containing compounds not easily obtainable by other methods.

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