Totally Synthetic by Paul H. Docherty, 26 October 2006
Total Synthesis of Manassantin A
S. Hanessian, G. J. Reddy, N. Chahal, Org. Lett. 2006, 5477-5480.
This C2 symmetric target shows an opportunity for a two directional synthesis, but as the other members of the family lack this feature, Hanessian et al used a more linear route for part of this synthesis. Most impressive (although by no means novel) was the methylation of the alkene, delivering two methyl groups in excellent d.r. Addition of lithium dimethylcuprate with TMSCl gave the anti product, which was enolised and alkylated with methyl iodide to give the syn diastereoisomer as the major product.
Other than that, this is a really nice total synthesis of a structurally interesting target, utilising the aforementioned symmetry to their advantage later in this paper for the title compound.
I may beg to disagree here. The first addition may actually produced silyketeneacetal first before it was hydrolyzed to the ester. However, for conjugated addition, many times you need TMSCl to activate the conjugated acceptor in order for the transformation to proceed. I don’t know which is the case here.
The TMSCl (or BF3 - Yamamoto cuprate) is needed to achieve conjugate addition to unsaturated esters; in this case nearly 20 equiv TMSCl and 6 equiv Gilman reagent! You can indeed trap that enolate with electrophiles, my guess is the selectivity stinks. The kinetics of the K-enolate (nucleophilicity) are far better than lithium, especially at -78, which translates into better selectivity. There is a paper which describes the mechansm of conjugate addition of cuprates vs alkyl copper species which I will try and dig up.
The review I was thinking of was done by Simon Woodward, Chem. Soc. Rev. (2000), 29, 393. A couple other of my favorite copper reviews: Nakamura, Angew. Chem. Int. Ed. (2000), 39, 3750 and Krause, Angew. Chem. Int. Ed. (1997), 39, 186.
For a related review on Yamamoto cuprates (very cool stuff): Yamamoto, Angew. Chem. Int. Ed. Engl. (1986), 25, 947
Agree, thought there would have been some method for trapping the enolate with a methyl. Maybe it had more to do with the selectivity of the addition, rather than that they couldn’t actually methylate.