Asymmetric Michael Addition Reaction of Phosphorus-Stabilized Allyl Anions with Cyclic Enones

Scott E Denmark, Jung Ho Kim

Research output: Contribution to journalArticle

Abstract

The asymmetric Michael addition reaction of chirally modified P-allyl anions derived from enantiomerically enriched 2-allyl-l,3,2-oxazaphosphorinane 2-oxides has been investigated with cyclic enone. The racemic 1,3,2-oxazaphosphorinane 2-oxide 3 has been shown to be extremely diastereoselective in the Michael addition to 5-, 6-, and 7-ring enones. With the enantiomerically enriched 2-allyl-1,3,2-oxazaphosphorinane 2-oxides, high regio- and diastereoselectivities (88-90% diastereomeric excess) have been achieved in the Michael addition reaction of one of the diastereomers (cis series). The Michael reaction of the anions derived from the trans series were not diastereoselective (~10% diastereomeric excess). The origin of the addition selectivity can be rationalized by (1) consideration of the structure and conformational preferences of the allyl anion (parallel conformation, s-trans, no lithium contact), (2) conformational analysis of the 1,3,2-oxazaphosphorinane 2-oxide ring (chair, equatorial allyl group) and (3) assumption of a 10-membered ring transition state structure with lithium coordination of the enon.

Original languageEnglish (US)
Pages (from-to)7535-7547
Number of pages13
JournalJournal of Organic Chemistry
Volume60
Issue number23
DOIs
StatePublished - Nov 1 1995

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Addition reactions
Phosphorus
Oxides
Anions
Lithium
Regioselectivity
Conformations

ASJC Scopus subject areas

  • Organic Chemistry

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Asymmetric Michael Addition Reaction of Phosphorus-Stabilized Allyl Anions with Cyclic Enones. / Denmark, Scott E; Kim, Jung Ho.

In: Journal of Organic Chemistry, Vol. 60, No. 23, 01.11.1995, p. 7535-7547.

Research output: Contribution to journalArticle

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abstract = "The asymmetric Michael addition reaction of chirally modified P-allyl anions derived from enantiomerically enriched 2-allyl-l,3,2-oxazaphosphorinane 2-oxides has been investigated with cyclic enone. The racemic 1,3,2-oxazaphosphorinane 2-oxide 3 has been shown to be extremely diastereoselective in the Michael addition to 5-, 6-, and 7-ring enones. With the enantiomerically enriched 2-allyl-1,3,2-oxazaphosphorinane 2-oxides, high regio- and diastereoselectivities (88-90{\%} diastereomeric excess) have been achieved in the Michael addition reaction of one of the diastereomers (cis series). The Michael reaction of the anions derived from the trans series were not diastereoselective (~10{\%} diastereomeric excess). The origin of the addition selectivity can be rationalized by (1) consideration of the structure and conformational preferences of the allyl anion (parallel conformation, s-trans, no lithium contact), (2) conformational analysis of the 1,3,2-oxazaphosphorinane 2-oxide ring (chair, equatorial allyl group) and (3) assumption of a 10-membered ring transition state structure with lithium coordination of the enon.",
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AB - The asymmetric Michael addition reaction of chirally modified P-allyl anions derived from enantiomerically enriched 2-allyl-l,3,2-oxazaphosphorinane 2-oxides has been investigated with cyclic enone. The racemic 1,3,2-oxazaphosphorinane 2-oxide 3 has been shown to be extremely diastereoselective in the Michael addition to 5-, 6-, and 7-ring enones. With the enantiomerically enriched 2-allyl-1,3,2-oxazaphosphorinane 2-oxides, high regio- and diastereoselectivities (88-90% diastereomeric excess) have been achieved in the Michael addition reaction of one of the diastereomers (cis series). The Michael reaction of the anions derived from the trans series were not diastereoselective (~10% diastereomeric excess). The origin of the addition selectivity can be rationalized by (1) consideration of the structure and conformational preferences of the allyl anion (parallel conformation, s-trans, no lithium contact), (2) conformational analysis of the 1,3,2-oxazaphosphorinane 2-oxide ring (chair, equatorial allyl group) and (3) assumption of a 10-membered ring transition state structure with lithium coordination of the enon.

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