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Link to original content: https://pubmed.ncbi.nlm.nih.gov/35076978
Origin of High Diastereoselectivity in Reactions of Seven-Membered-Ring Enolates - PubMed Skip to main page content
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. 2022 Mar 28;61(14):e202114183.
doi: 10.1002/anie.202114183. Epub 2022 Feb 15.

Origin of High Diastereoselectivity in Reactions of Seven-Membered-Ring Enolates

Olga Lavinda  1 , Collin H Witt  1 , K A Woerpel  1
Affiliations

Origin of High Diastereoselectivity in Reactions of Seven-Membered-Ring Enolates

Olga Lavinda et al. Angew Chem Int Ed Engl. .

Abstract

Unlike many reactions of their six-membered-ring counterparts, the reactions of chiral seven-membered-ring enolates are highly diastereoselective. Diastereoselectivity was observed for a range of substrates, including lactam, lactone, and cyclic ketone derivatives. The stereoselectivity arises from torsional and steric interactions that develop when electrophiles approach the diastereotopic π-faces of the enolates, which are distinguished by subtle differences in the orientation of nearby atoms of the ring.

Keywords: Conformational Analysis; Diastereoselectivity; Enolates; Seven-Membered-Rings; Torsional Strain.

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Figures

Figure 1:
Figure 1:
C4-substituted ε-lactam enolates. a) Transition state geometries of TS-26α and TS-26β. b) Enlarged Newman projections of enolate 26, TS-26α and TS-26β, viewing along the C2–C3 bond. c) Schematic depictions of Figure 1b.
Figure 2:
Figure 2:
C4-substituted δ-lactam enolates. a) Transition state geometries of TS-27α and TS-27β. b) Enlarged Newman projections of enolate 27, TS-27α and TS-27β, viewing along the C2–C3 bond. c) Schematic depictions of Figure 2b.
Figure 3:
Figure 3:
C5-substituted ε-lactam enolates. a) Transition state geometries of TS-34α and TS-34β. b) Enlarged Newman projections of enolate 34, TS-34α and TS-34β, viewing along the C2–C3 bond. c) Schematic depictions of Figure 3b.
Scheme 1.
Scheme 1.
Scope of stereoselectivity[a] of alkylations of C4-substituted ε-lactam enolates with various electrophiles. [a] Determined by 13C{1H} analysis of the crude reaction mixture.[16] [b] Isolated yield of purified product. [c] Product of the reaction of 1 with benzaldehyde. The ratio of syn- to anti-aldol adducts was 67:33.
Scheme 2.
Scheme 2.
Enolates of C6-substituted seven-membered-rings.
Scheme 3.
Scheme 3.
Alkylations of C6-substituted cycloheptanones. [a] Determined by 13C{1H} analysis of the crude reaction mixture.[16] [b] Isolated yield of purified product. [c] Product was synthesized by oxidation of the trimethylsilyl enol ether of 41.
Scheme 4:
Scheme 4:
Construction of α-carbon quaternary stereocenters. [a] The reaction was performed at −20 °C.
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