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Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination
In the most general practice of asymmetric catalysis, a chiral catalyst, typically bearing a center or an axis of chirality, is employed as the chiral source for imparting enantiocontrol over the developing product. Given the current interest toward optically pure compounds, various forms of chiral...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809490/ https://www.ncbi.nlm.nih.gov/pubmed/35222916 http://dx.doi.org/10.1039/d1sc05749a |
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author | Tribedi, Soumi Sunoj, Raghavan B. |
author_facet | Tribedi, Soumi Sunoj, Raghavan B. |
author_sort | Tribedi, Soumi |
collection | PubMed |
description | In the most general practice of asymmetric catalysis, a chiral catalyst, typically bearing a center or an axis of chirality, is employed as the chiral source for imparting enantiocontrol over the developing product. Given the current interest toward optically pure compounds, various forms of chiral induction enabled by diverse chiral sources as well as the use of multiple catalysts under one-pot conditions have been in focus. In one such promising development, an achiral N-sulfonamide protected 1,6-amino allyl alcohol (NaphSO(2)NHCH(2)C(Ph)(2)CH(2)CH[double bond, length as m-dash]CHCH(2)OH) was subjected to Tsuji–Trost activation and an intramolecular amination to form important chiral pyrrolidine frameworks. A dual catalytic system comprising Pd(PPh(3))(4) and DAPCy (β-cyclohexyl substituted double axially chiral phosphoric acid derived from two homocoupled BINOL backbones with a dynamic central chiral axis) under mild conditions was reported to offer quantitative conversion with an ee of 95%. Here, we provide molecular insights into the origin of chiral induction by DAPCy, as obtained through a comprehensive density functional theory (SMD((toluene))/B3LYP-D3/6-31G**,Pd(SDD)) investigation. Two key steps in the mechanism are identified to involve a cooperative mode of activation of the Pd-bound allyl alcohol in the form of a Pd-π-allyl moiety at one end of the substrate, followed by an intramolecular nucleophilic addition of N-sulfonamide from the other end to yield a pyrrolidine derivative bearing an α-vinyl stereogenic center. (S,R,S)-DAPCy is found to steer the dehydroxylation to yield a Pd-π-allyl intermediate with a suitably poised si prochiral face for the nucleophilic addition. In the enantiocontrolled (as well as the turn-over determining step) nucleophilic addition, the chiral catalyst is identified to serve as a chiral phosphate counterion. The chiral induction is facilitated by a series of N–H⋯O, C–H⋯O, C–H⋯π, lone pair (lp)⋯π, O–H⋯O, O–H⋯π, and π⋯π noncovalent interactions, which is noted as more effective in the lower energy C–N bond formation transition state through the si prochiral face of the Pd-π-allyl moiety. These insights into the novel dynamic axially double chiral catalyst could be valuable toward exploiting such modes of stereoinduction. |
format | Online Article Text |
id | pubmed-8809490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-88094902022-02-24 Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination Tribedi, Soumi Sunoj, Raghavan B. Chem Sci Chemistry In the most general practice of asymmetric catalysis, a chiral catalyst, typically bearing a center or an axis of chirality, is employed as the chiral source for imparting enantiocontrol over the developing product. Given the current interest toward optically pure compounds, various forms of chiral induction enabled by diverse chiral sources as well as the use of multiple catalysts under one-pot conditions have been in focus. In one such promising development, an achiral N-sulfonamide protected 1,6-amino allyl alcohol (NaphSO(2)NHCH(2)C(Ph)(2)CH(2)CH[double bond, length as m-dash]CHCH(2)OH) was subjected to Tsuji–Trost activation and an intramolecular amination to form important chiral pyrrolidine frameworks. A dual catalytic system comprising Pd(PPh(3))(4) and DAPCy (β-cyclohexyl substituted double axially chiral phosphoric acid derived from two homocoupled BINOL backbones with a dynamic central chiral axis) under mild conditions was reported to offer quantitative conversion with an ee of 95%. Here, we provide molecular insights into the origin of chiral induction by DAPCy, as obtained through a comprehensive density functional theory (SMD((toluene))/B3LYP-D3/6-31G**,Pd(SDD)) investigation. Two key steps in the mechanism are identified to involve a cooperative mode of activation of the Pd-bound allyl alcohol in the form of a Pd-π-allyl moiety at one end of the substrate, followed by an intramolecular nucleophilic addition of N-sulfonamide from the other end to yield a pyrrolidine derivative bearing an α-vinyl stereogenic center. (S,R,S)-DAPCy is found to steer the dehydroxylation to yield a Pd-π-allyl intermediate with a suitably poised si prochiral face for the nucleophilic addition. In the enantiocontrolled (as well as the turn-over determining step) nucleophilic addition, the chiral catalyst is identified to serve as a chiral phosphate counterion. The chiral induction is facilitated by a series of N–H⋯O, C–H⋯O, C–H⋯π, lone pair (lp)⋯π, O–H⋯O, O–H⋯π, and π⋯π noncovalent interactions, which is noted as more effective in the lower energy C–N bond formation transition state through the si prochiral face of the Pd-π-allyl moiety. These insights into the novel dynamic axially double chiral catalyst could be valuable toward exploiting such modes of stereoinduction. The Royal Society of Chemistry 2021-12-29 /pmc/articles/PMC8809490/ /pubmed/35222916 http://dx.doi.org/10.1039/d1sc05749a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Tribedi, Soumi Sunoj, Raghavan B. Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination |
title | Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination |
title_full | Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination |
title_fullStr | Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination |
title_full_unstemmed | Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination |
title_short | Molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination |
title_sort | molecular insights into chirality transfer from double axially chiral phosphoric acid in a synergistic enantioselective intramolecular amination |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809490/ https://www.ncbi.nlm.nih.gov/pubmed/35222916 http://dx.doi.org/10.1039/d1sc05749a |
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