Stereoselective Phosphine-Catalyzed Synthesis of Highly Functionalized Diquinanes

Stereoselective Phosphine-Catalyzed Synthesis of HighlyFunctionalized Diquinanes

Jonathan E. Wilson, Jianwei Sun, and Gregory C. Fu

DOI: http://dx.doi.org/10.1002/anie.200905125

While reviewing a nice paper from Overman I found this sweet one from Greg Fu and decided to present this to you first.

What we got here is a subsequent investigation of a procedure already published by Tomita et al. featuring a novel Baylis-Hillmann-like cyclization cascade:

The blue compounds represent the paper from Tomita et al., the red ones the paper featured in this review.

The reaction sequence is induced by the addition of about 20 mol% of tributylphopshine in a DCM/ethyl acetate mixture at room temperature to the starting material.

First a Michael addition of the phosphine to the alkyne yields an allenyl enolate which rapidly tautomerizes to an α-β-unsatured enolate. Next a Michael addition to the unsatured ester gives an ester enolate which reacts with the vinyl phosphine cation to from an ylide. This in turn yields after some tautomerization and catalyst regeneration the product:

The diastereoselectivity can easily be seen from the transition state:

Having established the right reaction conditions the group prepared some derivatives with the yields varying from 54% up to 89% respectively. Also the first formed 5 membered ring could be expanded to a 6 membered one without significant loss in yield.

And some studies towards further reactions of the produced diquinanes were employed featuring a Grignard reaction, Luche-reduction and Pd catalysed hydrogenation all in excellent diastereoselectivity:

Attempts to develop enantioselective reaction conditions by using a chiral phosphine gave very promising results:

On balance a nice reaction with some potential in natural product synthesis. What do you think?

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