Diastereodivergent synthesis of cyclopentyl boronic esters bearing contiguous fully substituted stereocentres Molly Fairchild, Adam Noble and Varinder K. Aggarwal University of Bristol,UK Natural products containing a carbocycle bearing two or more contiguous, quaternary stereocentres present a particular challenge to synthesis, not only in the construction of such a sterically congested motif but also in the control of stereochemistry. [1] Since a C‒B bond in a tertiary boronic ester can be directly and stereospecifically transformed into a C‒C bond for the formation of a quaternary stereocentre, [2] we envisaged that the stereocontrolled synthesis of densely substituted cycloalkyl boronic esters could provide rapid access to such highly-substituted, cyclic frameworks. Our work explored the reactivity of enantioenriched cyclic vinyl boronate complexes with varied substitution at the α-position, activated towards a ring contractive 1,2-metallate rearrangement by the addition of carbon- and hetereoatom-based electrophiles. [3] In this way, we were able to access a range of cyclopentyl boronic esters bearing contiguous, fully substituted stereocentres in an enantiospecific and highly diastereoselective manner. A remarkable diastereodivergency upon alteration of the reaction solvent was observed, allowing access to complementary diastereomeric pairs from the same starting materials. The utility of our methodology was demonstrated in the asymmetric synthesis of (+)-herbertene-1,14-diol, assembling the two contiguous, fully substituted stereocentres in our key ring contractive step and forging a new, highly sterically encumbered C‒C bond through the stereospecific transformation of the boronic ester.
References 1. M. Büschleb, S. Dorich, S. Hanessian, D. Tao, K. B. Schenthal, L. E. Overman, Angew. Chem. Int. Ed. 2016 , 55 , 4156–4186. 2. C. Sandford, V. K. Aggarwal, Chem. Commun. 2017 , 53 , 5481–5494. 3. M. E. Fairchild, A. Noble, V. K. Aggarwal, Angew. Chem. Int. Ed. 2022 , e202205816.
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