Stereochemistry of the allylation and crotylation reactions of alpha-methyl-beta-hydroxy aldehydes with allyl- and crotyltrifluorosilanes. Synthesis of anti,anti-dipropionate stereotriads and stereodivergent pathways for the reactions with 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes.
J Org Chem. 2003 Feb 21; 68(4):1319-33.JO

Abstract

A new method for the stereoselective synthesis of the anti,anti-dipropionate stereotriad via the reaction of alpha-methyl-beta-hydroxy aldehydes with (Z)-crotyltrifluorosilane (24) is described. These reactions were designed to occur through bicyclic transition states (e.g., 31) in which the silane reagent is covalently bound to the beta-hydroxyl group of the aldehyde and the crotyl group is transferred intramolecularly. This methodology was used to synthesize the C(7)-C(16) segment (58) of zincophorin, which contains a synthetically challenging all-anti stereopentad unit. Surprisingly, 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes react in a stereodivergent manner with 24: 2,3-anti-beta-hydroxy aldehydes give the targeted anti,anti-dipropionate adducts with high selectivity, but the reactions of 2,3-syn-beta-hydroxy aldehydes are poorly selective. The stereodivergent behavior of 2,3-syn- vs 2,3-anti-alpha-methyl-beta-hydroxy aldehydes is also exhibited in their reactions with the allyl- (68) and (E)-crotyltrifluorosilanes (27). Competition experiments performed with beta-hydroxy aldehydes 37a (anti) and the corresponding p-methoxybenzyl (PMB) ether 48, and between aldehyde 39 (syn) and the PMB ether 90, established that the 2,3-anti-beta-hydroxy aldehydes react predominantly through bicyclic transition states while the 2,3-syn aldehydes react predominantly through conventional Zimmerman-Traxler transition states. NMR studies established that both the 2,3-syn and the 2,3-anti aldehydes form stable, pentavalent silicate intermediates (98 and 100) with PhSiF(3), but chelated structures 99 and 101 could not be detected. The activation energies for the competing bicyclic and conventional Zimmerman-Traxler transition states were calculated by using semiemperical methods (MNDO/d). These calculations indicate that the stereodivergent behavior of the 2,3-syn-beta-hydroxy aldehydes and the 2,3-anti-beta-hydroxy aldehydes is due to differences in nonbonded interactions in the bicyclic transition states. Specifically, nonbonded interactions in the bicyclic transition states for the allylation/crotylation reactions of the 2,3-syn-beta-hydroxy aldehydes permits the traditional Zimmerman-Traxler transition states to be preferentially utilized.

Authors+Show Affiliations

Chemler SR

Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. schemler@buffalo.edu

Roush WR

No affiliation info available

MeSH

AldehydesCatalysisCyclizationIndicators and ReagentsModels, MolecularMolecular StructureSilanesStereoisomerismStructure-Activity Relationship

Pub Type(s)

Comparative Study

Journal Article

Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12585871

Citation

Chemler, Sherry R., and William R. Roush. "Stereochemistry of the Allylation and Crotylation Reactions of Alpha-methyl-beta-hydroxy Aldehydes With Allyl- and Crotyltrifluorosilanes. Synthesis of Anti,anti-dipropionate Stereotriads and Stereodivergent Pathways for the Reactions With 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy Aldehydes." The Journal of Organic Chemistry, vol. 68, no. 4, 2003, pp. 1319-33.

Chemler SR, Roush WR. Stereochemistry of the allylation and crotylation reactions of alpha-methyl-beta-hydroxy aldehydes with allyl- and crotyltrifluorosilanes. Synthesis of anti,anti-dipropionate stereotriads and stereodivergent pathways for the reactions with 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes. J Org Chem. 2003;68(4):1319-33.

Chemler, S. R., & Roush, W. R. (2003). Stereochemistry of the allylation and crotylation reactions of alpha-methyl-beta-hydroxy aldehydes with allyl- and crotyltrifluorosilanes. Synthesis of anti,anti-dipropionate stereotriads and stereodivergent pathways for the reactions with 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes. The Journal of Organic Chemistry, 68(4), 1319-33.

Chemler SR, Roush WR. Stereochemistry of the Allylation and Crotylation Reactions of Alpha-methyl-beta-hydroxy Aldehydes With Allyl- and Crotyltrifluorosilanes. Synthesis of Anti,anti-dipropionate Stereotriads and Stereodivergent Pathways for the Reactions With 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy Aldehydes. J Org Chem. 2003 Feb 21;68(4):1319-33. PubMed PMID: 12585871.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Stereochemistry of the allylation and crotylation reactions of alpha-methyl-beta-hydroxy aldehydes with allyl- and crotyltrifluorosilanes. Synthesis of anti,anti-dipropionate stereotriads and stereodivergent pathways for the reactions with 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes. AU - Chemler,Sherry R, AU - Roush,William R, PY - 2003/2/15/pubmed PY - 2003/10/21/medline PY - 2003/2/15/entrez SP - 1319 EP - 33 JF - The Journal of organic chemistry JO - J Org Chem VL - 68 IS - 4 N2 - A new method for the stereoselective synthesis of the anti,anti-dipropionate stereotriad via the reaction of alpha-methyl-beta-hydroxy aldehydes with (Z)-crotyltrifluorosilane (24) is described. These reactions were designed to occur through bicyclic transition states (e.g., 31) in which the silane reagent is covalently bound to the beta-hydroxyl group of the aldehyde and the crotyl group is transferred intramolecularly. This methodology was used to synthesize the C(7)-C(16) segment (58) of zincophorin, which contains a synthetically challenging all-anti stereopentad unit. Surprisingly, 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes react in a stereodivergent manner with 24: 2,3-anti-beta-hydroxy aldehydes give the targeted anti,anti-dipropionate adducts with high selectivity, but the reactions of 2,3-syn-beta-hydroxy aldehydes are poorly selective. The stereodivergent behavior of 2,3-syn- vs 2,3-anti-alpha-methyl-beta-hydroxy aldehydes is also exhibited in their reactions with the allyl- (68) and (E)-crotyltrifluorosilanes (27). Competition experiments performed with beta-hydroxy aldehydes 37a (anti) and the corresponding p-methoxybenzyl (PMB) ether 48, and between aldehyde 39 (syn) and the PMB ether 90, established that the 2,3-anti-beta-hydroxy aldehydes react predominantly through bicyclic transition states while the 2,3-syn aldehydes react predominantly through conventional Zimmerman-Traxler transition states. NMR studies established that both the 2,3-syn and the 2,3-anti aldehydes form stable, pentavalent silicate intermediates (98 and 100) with PhSiF(3), but chelated structures 99 and 101 could not be detected. The activation energies for the competing bicyclic and conventional Zimmerman-Traxler transition states were calculated by using semiemperical methods (MNDO/d). These calculations indicate that the stereodivergent behavior of the 2,3-syn-beta-hydroxy aldehydes and the 2,3-anti-beta-hydroxy aldehydes is due to differences in nonbonded interactions in the bicyclic transition states. Specifically, nonbonded interactions in the bicyclic transition states for the allylation/crotylation reactions of the 2,3-syn-beta-hydroxy aldehydes permits the traditional Zimmerman-Traxler transition states to be preferentially utilized. SN - 0022-3263 UR - https://www.unboundmedicine.com/medline/citation/12585871/Stereochemistry_of_the_allylation_and_crotylation_reactions_of_alpha_methyl_beta_hydroxy_aldehydes_with_allyl__and_crotyltrifluorosilanes__Synthesis_of_antianti_dipropionate_stereotriads_and_stereodivergent_pathways_for_the_reactions_with_23_anti__and_23_syn_alpha_methyl_beta_hydroxy_aldehydes_ DB - PRIME DP - Unbound Medicine ER -

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