Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions

Wesley J. Olivier; Rasool Babaahmadi; Nigel T. Lucas; Alireza Ariafard; Alex C. Bissember; Jason A. Smith

doi:10.1021/acs.orglett.1c03205

Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions

Wesley J. Olivier, Rasool Babaahmadi, Nigel T. Lucas, Alireza Ariafard, Alex C. Bissember^*, Jason A. Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Letter › peer-review

11 Citations (Scopus)

Abstract

This report investigates the fundamental basis for rather surprising patterns of reactivity in Brønsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.

Original language	English
Pages (from-to)	8494-8498
Number of pages	5
Journal	Organic Letters
Volume	23
Issue number	21
DOIs	https://doi.org/10.1021/acs.orglett.1c03205
Publication status	Published - 5 Nov 2021
Externally published	Yes

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10.1021/acs.orglett.1c03205

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title = "Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions",

abstract = "This report investigates the fundamental basis for rather surprising patterns of reactivity in Br{\o}nsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.",

author = "Olivier, \{Wesley J.\} and Rasool Babaahmadi and Lucas, \{Nigel T.\} and Alireza Ariafard and Bissember, \{Alex C.\} and Smith, \{Jason A.\}",

note = "Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

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doi = "10.1021/acs.orglett.1c03205",

language = "English",

volume = "23",

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journal = "Organic Letters",

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TY - JOUR

T1 - Exploring Cyclization Strategies to Access Stemona Alkaloids

T2 - Subtle Effects Influencing Reactivity in Intramolecular Michael Additions

AU - Olivier, Wesley J.

AU - Babaahmadi, Rasool

AU - Lucas, Nigel T.

AU - Ariafard, Alireza

AU - Bissember, Alex C.

AU - Smith, Jason A.

PY - 2021/11/5

Y1 - 2021/11/5

N2 - This report investigates the fundamental basis for rather surprising patterns of reactivity in Brønsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.

AB - This report investigates the fundamental basis for rather surprising patterns of reactivity in Brønsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.

UR - https://www.scopus.com/pages/publications/85118716030

U2 - 10.1021/acs.orglett.1c03205

DO - 10.1021/acs.orglett.1c03205

M3 - Letter

C2 - 34677072

AN - SCOPUS:85118716030

SN - 1523-7060

VL - 23

SP - 8494

EP - 8498

JO - Organic Letters

JF - Organic Letters

IS - 21

ER -

Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions

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