A Modular Approach for the Synthesis of Natural and Artificial Terpenoids.

Many terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem-stamp strategy for the construction of the key isoprene unit, which consists of two steps: one-carbon extension of aldehydes to the alkenyl boronates by the boron-Wittig reaction and the rhodium-catalyzed reaction of alkenyl boronates with 2,3-allenols to yield enals. This chem-stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, ß-carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3-allenols, creation of new non-natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups.

Direct Synthesis of α-Allenols from TMS-Protected Alkynes and Aldehydes Mediated by Tetrabutylammonium Fluoride.

A unique chemoselective synthesis of α-allenic alcohols is presented. Tetrabutylammonium fluoride (TBAF) mediated this transformation under mild reaction conditions. A range of functional groups is well-tolerated in this reaction, while affording adducts in moderate to excellent yields (48-96 %, average 76 %). Mechanistic studies, including the use of tetrabutylammonium hydroxide (TBAH), revealed that the hydroxide ion can be the responsible for the observed rearrangement.