Cobalt-Catalyzed Diastereoselective Reductive [3 + 2] Cycloaddition of Allenes and Enones

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/asap/abs/ja0710196.html

From Prof. Chien-Hong Cheng's group at National Tsing Hua University, Taiwan

This is quite an interesting and intriguing chemistry. The new Co-mediated [3+2] cycloaddition of an allene and alpha,beta-unsaturated ketone was recently reported in JACS ASAP. The method is highly diasteroeselective and seems efficient in generating a variety of 3-methylene-cyclopentanols.

The catalyst system consisted of CoI2(dppe), Zn, ZnI2, and water in CH3CN. ZnI2 was crucial for the reaction to proceed, without which there was no reaction. The reaction partners were heated with the catalyst and co-catalyst at 80 C for several hours. The products were obtained in good yields. In the case where the allene partner was the phenyl allene, the enone partner, which reacted as the three-carbon partners, cycloadded to the internal double bond of the allene to give the desired cyclopentanol as a single diastereomer.

As seen in entries 10-12, when the allene partner was naphthalene and ortho-methylphenyl allene, the products were obtained as diastereomeric mixtures, still in excellent selectivity. This method complements well with the existing [3+2] method where the allene reacts as the three-carbon partner and the enone as the two-carbon component.

When the allene partner contained an ester functionality, the initial cyclopantanol adduct readily cyclized to give fused lactone products.

In probing the mechanism of the reaction and the role of water, D2O was used in placed of H2O and it was found that deuterium was incorporated to the 5-position of the carbocycle as well as on the oxygen of the alcohol.

Thus, initially, the mechanism was proposed as followed. The cobalt inserted into the internal double bond of allene and the double bond of the enone to form cobaltocycle 4. This intermediate is expected to be in equilibrium with the enolate derivative which then got quenched with D2O or H2O. The resulting carbonyl in 5 was added nucleophilically with the Co-C bond and thus formed the Co-O bond, which picked up another deuterium or proton from D2O or H2O, respectively.

This is quite cool chemistry and is expected to find numerous uses as a tool in total synthesis of natural products.