Synthesis of Enantioenriched Tertiary Boronic Esters from Secondary Allylic Carbamates – Application to the Synthesis of C30 Botryococcene

Alexander P. Pulis and Varinder K. Aggarwal J. Am. Chem. Soc.
DOI: 10.1021/ja303022d

The Aggarwal group have developed a route to tertiary alcohols by a lithiation-borylation-oxidation process from secondary allylic carbamates.

This approach has previously been applied to benzylic carbamates where the aryl substituent is necessary to facilitate deprotonation. Employing an allyl substituent acidifies the α-proton, while configurational stability of the lithiated species is aided by the substitution around the lithiated centre and coordination of the carbonyl oxygen to lithium. However, previous work by Hoppe has shown that upon addition of an electrophile a mixture of products is observed resulting from α- and γ-substitution.

Despite this precedent, addition of a boronic ester gives only the desired product of α-substitution with almost complete retention of stereochemistry.

In the reaction sequence, the boronic acid displaces lithium with retention of stereochemistry. The alkyl group of the boronic ester then displaces the carbamate. The boronic ester can then be oxidised to give the tertiary alcohol or be used in cross coupling reactions.

The scope of the reaction has been explored and alkyl, allyl, phenyl and vinyl boronic esters are all supported with high yields and er.

The methodology is then exemplified in a concise synthesis of triterpenoid Botryococcene and its C10 epimer which nicely demonstrates that stereocontrol is not governed by the substrate.

Also of note is that during the synthesis of Botryococcene, when the attempted Zweifel olefination failed, a novel olefination reaction was employed.

Trans-metalation of the epoxy stannane with BuLi followed by trapping with the boronate and rearrangement gives β-alkoxy boronic ester which can then eliminate to give the olefin upon treatment with Ghosez reagent.


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