1,5-anti stereocontrol in the boron-mediated aldol reactions of beta-alkoxy methyl ketones: the role of the formyl hydrogen bond

The Journal of Organic Chemistry
Robert S Paton, Jonathan M Goodman

Abstract

The boron-mediated aldol reactions of certain types of beta-alkoxy methyl ketone show remarkably high levels of stereoinduction with achiral aldehydes, leading preferentially to 1,5-anti related stereocenters. Given the low levels of asymmetric induction usually observed in acetate aldol reactions, this is of great synthetic utility and has been used successfully in the total synthesis of a number of polyketide natural products. We have investigated the effects of the alkoxy protecting group (OMe, OPMB, PMP acetal, tetrahydropyran, and OTBS) present in the boron enolate on the level and sense of remote 1,5-stereoinduction, using density functional theory calculations (B3LYP/6-31G**). Our predictions of diastereoselectivity from comparison of the competing aldol transition structures are in excellent qualitative and quantitative agreement with experimentally reported values. We conclude that the boron aldol reactions of unsubstituted boron enolates proceed via boat-shaped transition structures in which a stabilizing formyl hydrogen bond exists between the alkoxy oxygen and the aldehyde proton. It is this interaction that leads to preferential formation of the 1,5-anti adduct, by minimizing steric interactions between the beta-al...Continue Reading

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Citations

Dec 10, 2015·Organic Letters·Luiz C Dias, Emílio C de Lucca
Aug 10, 2016·The Journal of Organic Chemistry·Elodie BrunJanine Cossy
Feb 22, 2017·The Journal of Organic Chemistry·Luiz C Dias, Emilio C de Lucca
Jan 23, 2016·Organic & Biomolecular Chemistry·Luiz C DiasEliezer J Barreiro
Feb 20, 2015·Organic & Biomolecular Chemistry·L C DiasE C de Lucca
Jul 8, 2017·The Journal of Organic Chemistry·Zirong Zhang, David B Collum
Jan 3, 2019·Chemistry : a European Journal·Camille LecourtJanick Ardisson
Aug 21, 2009·Natural Product Reports·Martin E Maier
Mar 7, 2019·Organic & Biomolecular Chemistry·Alessandra A G FernandesLuiz Carlos Dias
Jul 1, 2016·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Pablo BarrioSantos Fustero
Apr 17, 2012·Organic & Biomolecular Chemistry·Ian PatersonChristian Moessner
Aug 8, 2008·Angewandte Chemie·Michael E GreenPaul E Floreancig
Jul 31, 2013·Angewandte Chemie·S B Jennifer KanIan Paterson
Jul 5, 2013·Organic & Biomolecular Chemistry·Ryne C Johnston, Paul Ha-Yeon Cheong
Aug 17, 2019·Chirality·Gaspar Diaz-MuñozMarisa Alves Nogueira Diaz
Apr 3, 2020·Chemistry : a European Journal·Robert R A FreundHans-Dieter Arndt
May 20, 2009·The Journal of Organic Chemistry·Dale E WardM Mehdi Zahedi
Jul 12, 2008·The Journal of Organic Chemistry·Luiz C DiasAndrea M Aguilar
Mar 25, 2009·Journal of Chemical Information and Modeling·Robert S Paton, Jonathan M Goodman
Jul 12, 2011·The Journal of Organic Chemistry·Joana ZambranaCristina Luján
Jan 14, 2012·Journal of the American Chemical Society·Matthew N GraysonJonathan M Goodman
Jul 16, 2014·Organic Letters·Patrick B BradyHisashi Yamamoto
Sep 10, 2011·Journal of the American Chemical Society·Shuangyi WanPaul E Floreancig

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