Opposing auxiliary conformations produce the same torquoselectivity in an oxazolidinone-directed Nazarov cyclization

Flynn, Bernard L., Manchala, Narasimhulu and Krenske, Elizabeth H. (2013) Opposing auxiliary conformations produce the same torquoselectivity in an oxazolidinone-directed Nazarov cyclization. Journal of the American Chemical Society, 135 24: 9156-9163. doi:10.1021/ja4036434

Author Flynn, Bernard L.
Manchala, Narasimhulu
Krenske, Elizabeth H.
Title Opposing auxiliary conformations produce the same torquoselectivity in an oxazolidinone-directed Nazarov cyclization
Journal name Journal of the American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
Publication date 2013-06-19
Year available 2013
Sub-type Article (original research)
DOI 10.1021/ja4036434
Open Access Status Not yet assessed
Volume 135
Issue 24
Start page 9156
End page 9163
Total pages 8
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Formatted abstract
Most applications of chiral oxazolidinone auxiliaries in asymmetric synthesis operate through a common set of stereocontrol principles. That is, the oxazolidinone is made to adopt a specific, coplanar conformation with respect to the prochiral substrate, and reaction occurs preferentially at whichever stereoheterotopic face is not blocked by the substituents on the oxazolidinone. In contrast to these principles, we report here the discovery of an alternative mechanism of oxazolidinone-based stereocontrol that does not require coplanarity and is driven instead by allylic strain. This pathway has been uncovered through computational studies of an asymmetric Nazarov cyclization. Chiral oxazolidinone auxiliaries provide essentially complete control over the torquoselectivity of ring closure and the regioselectivity of subsequent deprotonation. Density functional theory calculations (M06-2X//B3LYP) reveal that in the transition state of 4π electrocyclic ring closure, the oxazolidinone ring and the cyclizing pentadienyl cation are distorted from coplanarity in a manner that gives two transition state conformations of similar energy. These two conformers are distinguished by a 180° flip in the auxiliary orientation such that in one conformer the oxazolidinone carbonyl is oriented toward the OH of the pentadienyl cation (syn-conformer) and in the other it is oriented away from this OH (anti-conformer). Surprisingly, both conformations induce the same sense of torquoselectivity, with a 3–5 kcal/mol preference for the C5-β epimer of the ring-closed cation. In both conformations, the conrotatory mode that leads to the C5-α epimer is disfavored due to higher levels of allylic strain between the oxazolidinone substituent and adjacent groups on the pentadienyl cation (R4 and OH). The excellent torquoselectivities obtained in the oxazolidinone-directed Nazarov cyclization suggest that the allylic strain-driven stereoinduction pathway represents a viable alternative mechanism of stereocontrol for reactions of sterically congested substrates that lie outside of the traditional coplanar (N-acyloxazolidinone) paradigm.
Keyword Diels-Alder cycloaddition
Dynamic kinetic resolution
Asymmetric cyclopentannelation
Cationic cyclopentannelation
Density functionals
Aldol reactions
Singlet oxygen
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP0985623
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
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Created: Fri, 04 Oct 2013, 21:14:35 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences