Enantioselective [4 + 2] Cycloadditions of o-Quinone Methides:  Total Synthesis of (+)-Mimosifoliol and Formal Synthesis of (+)-Tolterodine.

Abstract

The structure of (+)-R-tolterodine (1) shown in the Table of Contents graphic is missing a double bond due to a processing error. The structure was corrected on the Web on January 28, 2005. The correct Table of Contents graphic is shown below.

Natural Product Synthesis Using Multicomponent Reaction Strategies

“…To demonstrate the usefulness of this three-component reaction cascade, Selenski and Pettus targeted the total synthesis of a Leguminosae rootwood component, (+)mimosifoliol (225, Scheme 35), 98 which was completed in nine steps and 35% overall yield. 99,100 As discussed above, The formal synthesis of (+)-tolterodine, a related natural product, was also accomplished using a similar multicomponent reaction process. 100…”

“…The requisite alcohol precursor for the chiral enol ether is commercially available under both enantiomeric forms. To demonstrate the usefulness of this three-component reaction cascade, Selenski and Pettus targeted the total synthesis of a Leguminosae rootwood component, (+)-mimosifoliol ( 225 , Scheme ), which was completed in nine steps and 35% overall yield. , As discussed above, the key three-component reaction requires an ortho -substituted t -Boc salicylaldehyde as substrate. Here, trihydroxylated benzaldehyde 226 was treated with phenylmagnesium bromide in the presence of trans-2-phenyl-1-cyclohexanol vinyl ether 227 (Scheme ).…”

“…A concise series of functional group modifications led to synthetic (+)-mimosifoliol ( 225 ). The formal synthesis of (+)-tolterodine, a related natural product, was also accomplished using a similar multicomponent reaction process …”

Brønsted Acid-Catalyzed, Diastereo- and Enantioselective, Intramolecular Oxa-Diels–Alder Reaction of ortho-Quinone Methides and Unactivated Dienophiles

“…3 Despite the enormous synthetic potential residing within o-QMs catalytic, enantioselective transformations of these entities have been developed only quite recently. Early contributions to organometallic and transition-metal-mediated processes have been accomplished by Pettus et al, 4 who employed a substrate-controlled enantioselective cycloaddition, and by Sigman and co-workers, 5 wherein a confined chiral Pd-o-QM complex furnished various alkene difunctionalization reactions. Further reports aimed at organocatalytic activation modes, such as the formal [4 + 2]-cycloaddition of a preformed o-QM with various silylketene acetals mediated by cinchona alkaloid-derived catalysts by Lectka et al 6 Starting from either stable or in situ-generated o-QMs, the group of Schaus accomplished the addition of aryl and vinyl boronates with 3,3′-dibromobinaphthol as catalyst, proceeding under very mild conditions in up to a 96:04 enantiomeric ratio (er).…”