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Reductive openings of benzylidene acetals revisited: a mechanistic scheme for regio- and stereoselectivity.

Johnsson, Richard LU ; Ohlin, Markus LU and Ellervik, Ulf LU (2010) In Journal of Organic Chemistry 75(23). p.8003-8011
Abstract
Despite the importance of regioselective reductive openings of cyclic acetals, mechanistic details are scarce. In this study 4,6-O-benzylidene acetals were used as model compounds for deciphering the mechanism of regioselective openings using a variety of reducing agents. Competitive isotopic studies aiming at primary and secondary isotope effects, as well as an electron-deficient substrate, were used to evaluate stereo- and regioselectivity. We show that there are three distinctly different mechanistic pathways. In nonpolar solvents, such as toluene, the acetal is activated by the very reactive naked Lewis acid to give a fully developed oxocarbenium ion that is then reduced by the borane, with low stereoselectivity. In THF the reactivity... (More)
Despite the importance of regioselective reductive openings of cyclic acetals, mechanistic details are scarce. In this study 4,6-O-benzylidene acetals were used as model compounds for deciphering the mechanism of regioselective openings using a variety of reducing agents. Competitive isotopic studies aiming at primary and secondary isotope effects, as well as an electron-deficient substrate, were used to evaluate stereo- and regioselectivity. We show that there are three distinctly different mechanistic pathways. In nonpolar solvents, such as toluene, the acetal is activated by the very reactive naked Lewis acid to give a fully developed oxocarbenium ion that is then reduced by the borane, with low stereoselectivity. In THF the reactivity of the Lewis acid is moderated by complex formation with the solvent. These reactions are thus much slower and proceed through an intimate ion pair and thereby show high stereoselectivities. The regioselectivity in these reactions is directed by the interaction between the Lewis acid and the most nucleophilic oxygen of the acetal, thus yielding a free 6-hydroxyl group. Finally, boranes such as BH(3)·NMe(3) are activated by Lewis acid, which results in the borane being the most electrophilic species, and consequently the reaction shows inversed regioselectivity to give a free 4-hydroxyl group. These reactions proceed through an oxocarbenium ion and thus show low stereoselectivity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Organic Chemistry
volume
75
issue
23
pages
8003 - 8011
publisher
The American Chemical Society
external identifiers
  • wos:000284519900003
  • pmid:21033762
  • scopus:78650303107
ISSN
1520-6904
DOI
10.1021/jo101184d
language
English
LU publication?
yes
id
ef15ce22-0dca-4c0b-88a0-2b7c81c4b2c6 (old id 1732581)
date added to LUP
2010-12-16 14:29:19
date last changed
2018-05-29 09:51:27
@article{ef15ce22-0dca-4c0b-88a0-2b7c81c4b2c6,
  abstract     = {Despite the importance of regioselective reductive openings of cyclic acetals, mechanistic details are scarce. In this study 4,6-O-benzylidene acetals were used as model compounds for deciphering the mechanism of regioselective openings using a variety of reducing agents. Competitive isotopic studies aiming at primary and secondary isotope effects, as well as an electron-deficient substrate, were used to evaluate stereo- and regioselectivity. We show that there are three distinctly different mechanistic pathways. In nonpolar solvents, such as toluene, the acetal is activated by the very reactive naked Lewis acid to give a fully developed oxocarbenium ion that is then reduced by the borane, with low stereoselectivity. In THF the reactivity of the Lewis acid is moderated by complex formation with the solvent. These reactions are thus much slower and proceed through an intimate ion pair and thereby show high stereoselectivities. The regioselectivity in these reactions is directed by the interaction between the Lewis acid and the most nucleophilic oxygen of the acetal, thus yielding a free 6-hydroxyl group. Finally, boranes such as BH(3)·NMe(3) are activated by Lewis acid, which results in the borane being the most electrophilic species, and consequently the reaction shows inversed regioselectivity to give a free 4-hydroxyl group. These reactions proceed through an oxocarbenium ion and thus show low stereoselectivity.},
  author       = {Johnsson, Richard and Ohlin, Markus and Ellervik, Ulf},
  issn         = {1520-6904},
  language     = {eng},
  number       = {23},
  pages        = {8003--8011},
  publisher    = {The American Chemical Society},
  series       = {Journal of Organic Chemistry},
  title        = {Reductive openings of benzylidene acetals revisited: a mechanistic scheme for regio- and stereoselectivity.},
  url          = {http://dx.doi.org/10.1021/jo101184d},
  volume       = {75},
  year         = {2010},
}