David S. Watt

The Silylation of Nitrile Anions. Silylketenimines

Abstract The ambident anion lc↔ln derived from proton abstraction from the α position of primary and secondary nitriles offers two potential sites for electrophilic attack.1

Synthetic Approaches to Taxodione. Synthesis of Methyl 12-Oxopodocarpa-5,9(11)-diene-8β-Carboxylate

Abstract In connection with studies leading to the total synthesis of taxodione1 (1), we required the tricyclic enone 3. We have previously described2 an AB→ABC approach to this intermediate which was flawed by a low yield in the penultimate closure of the C ring (2→3). We now wish to report an alternate synthesis of 3 which involves a BC→ABC approach for the construction of this tricyclic system.

A Convenient Synthesis of 3-Methoxyphthalic Anhydride

Abstract Many antibiotics of the anthracycline family1 possess structures for which 3-methoxyphthalic anhydride (1) would be a suitable synthon2 in a total synthesis. A classic synthesis of (1) has employed 3-nitrophthalic acid3 but, in our hands, proceeded in low overall yield. Recent syntheses have utilized the Diels Alder reaction of dimethyl acetylenedicarboxylate (2) with 1-methoxy-1,3-cyclohexadiene,4 1,4-diacetoxybutadiene,5 2-acetoxyfuran,6 2-methoxyfuran7 or furan8 to obtain 3-hydroxyphthalic acid or a derivative. We now wish to report a convenient Diels-Alder synthesis of (1) from 3-methoxy-2-pyrone (3).

Robinson Annulations of Sterically Hindered α-Carbomethoxycyclohexanones

Abstract In conjunction with our interest in the synthesis of quassinoids such as bruceantin1 (1), we required a synthesis of a tricyclic intermediate bearing a functionalized angular methyl group at C-8. One approach which we considered involved the Robinson annulation2 of a bicyclic β-ketoester 2 and methyl vinyl ketone to obtain the tricyclic enone 3. The major obstacle in such an approach involved the Aldol condensation step in the annulation process in which an enolate at C-11 must condense with a highly substituted carbonyl group at C-9. There are conflicting reports in the literature on the success of similar condensations,3,4 and we elected to test the feasibility of this approach.

A synthesis of (±)-cryptojaponol and (±)-taxodione

Abstract A new method for the synthesis of highly substituted catechols involving the decarboxylation of an α,β-epoxyenone was developed and employed in a synthesis of two diterpenes, cryptojaponol and taxodione.

A Stereoselective α-Hydroxylation of Cyclohexanecarbonitriles

Abstract The traditional approach to the synthesis of cyanohydrins from carbonyl compounds was augmented by a recent approach involving the α-hydroxylation of nitriles.1 Each synthetic method possesses certain limitations and yet offers distinct advantages in scope.2 Although both methods provide useful syntheses of cyanohydrins of cyclohexanones, it was of interest to contrast the stereoselectivity of the nitrile and ketone approach in cyclohexyl systems.