Recent Advances in Carbocyclic Ketone Construction
As the ketone is the central functional group of organic synthesis, so cyclic
ketone construction has dominated carbocyclic construction. Several powerful
methods for cyclic ketone construction have recently been put forward.
Cyclic ketones can also be formed by intramolecular aldol condensation. Roger C. Whitehead of the University of Manchester found (Tetrahedron Lett. 2005, 46, 2803. ) that the cis ene dione 4, available by oxidation of the corresponding furan 3, underwent highly diasteroselective aldol condensation, to give untenone A (5).
The intramolecular aldol condensation can also be used to prepare enantiomerically-pure cyclic enones. Shigefumi Kuwahara of Tohoku University has shown (Tetrahedron Lett. 2005, 46, 547. ) that addition of 6 to 7, following the Evans procedure, followed by reduction and silylation delivered the bis-ether 8. Wacker oxidation followed by ozonolysis and exposure to aqueous NaOH in ether then led to the enone 9, without epimerization of the γ-center.
Scott G. Nelson of the University of Pittsburgh has developed (J. Org. Chem. 2005, 70, 4375. ) a highly diastereocontrolled route to substituted cyclohexanones using the intramolecular Sakurai reaction. The requisite allyl silane 12 was prepared by Claisen rearrangement of the allylic alcohol 10, followed by homologation. The Ti enolate from the Sakurai addition was trapped with isobutyraldehyde to give 13. Although 32 diastereomers of 13 are possible, the diastereomer illustrated was the dominant product from the cylization. Note that use of the enantiomerically-pure form of the alcohol 10 would have led to enantiomerically-pure 13.
One of the most powerful methods for bicyclic ketone construction is the intramolecular Pauson-Khand reaction (14 -> 15). Although catalytic methods for this transformation have been put forward, they are not always successful. Jihua Chen and Zhen Yang of Peking University have now found (Org. Lett. 2005, 7, 593. ) that the cyclization proceeds quickly and efficiently with 5 mol % of the commercial grade of Co2(CO)8 if it is run in the presence of the inexpensive tetramethylthiourea. The authors have also reported (Org. Lett. 2005, 7, 1657. ) that TMTU is beneficial to the Pd-catalyzed version of the reaction. These advances will make the Pauson-Khand cyclization a more generally practical procedure.