Stereoselective synthesis of exocyclic allenes by double hydride reduction of 3-alkynyl-2-cycloalkenones

Matthew A. Gubbels, Martin Hulce, John M. Kum, Andrew K. Urick, Eric Villa

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Exocyclic allene natural products and pharmaceutical agents are rare but interesting compounds: Fucoxanthin, grasshopper ketone, and analogues of prostacyclins, cephalosporins, antithrombic agents and sterol biosynthesis inhibitors are representative. Syntheses of exocyclic allenes commonly rely on extended conjugate additions to e.g., alk-2-en-4-ynones, syn SN2′-like additions to alkynyl oxiranes, and substitution reactions such as electrophilic substitutions of propargylic silanes. We report that the reaction of 3-alkynyl-2-cycloalkenones with 2 equiv of various hydridoaluminates but not hydridoborates proceeds via diastereoselective 1,4-reduction of a vinylogously propargylic intermediate alcoholate to provide exocyclic allenes as major products. Isomeric 3-alkynylcycloalkanols also are observed.

Original languageEnglish (US)
Pages (from-to)6052-6063
Number of pages12
JournalTetrahedron
Volume72
Issue number40
DOIs
StatePublished - Oct 6 2016

Fingerprint

Hydrides
Prostaglandins I
Substitution reactions
Silanes
Epoxy Compounds
Biosynthesis
Sterols
Cephalosporins
Biological Products
Pharmaceutical Preparations
propadiene
grasshopper ketone
fucoxanthin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Stereoselective synthesis of exocyclic allenes by double hydride reduction of 3-alkynyl-2-cycloalkenones. / Gubbels, Matthew A.; Hulce, Martin; Kum, John M.; Urick, Andrew K.; Villa, Eric.

In: Tetrahedron, Vol. 72, No. 40, 06.10.2016, p. 6052-6063.

Research output: Contribution to journalArticle

Gubbels, Matthew A. ; Hulce, Martin ; Kum, John M. ; Urick, Andrew K. ; Villa, Eric. / Stereoselective synthesis of exocyclic allenes by double hydride reduction of 3-alkynyl-2-cycloalkenones. In: Tetrahedron. 2016 ; Vol. 72, No. 40. pp. 6052-6063.
@article{de960e7301b94c199f0c7fc1f1dfbcc9,
title = "Stereoselective synthesis of exocyclic allenes by double hydride reduction of 3-alkynyl-2-cycloalkenones",
abstract = "Exocyclic allene natural products and pharmaceutical agents are rare but interesting compounds: Fucoxanthin, grasshopper ketone, and analogues of prostacyclins, cephalosporins, antithrombic agents and sterol biosynthesis inhibitors are representative. Syntheses of exocyclic allenes commonly rely on extended conjugate additions to e.g., alk-2-en-4-ynones, syn SN2′-like additions to alkynyl oxiranes, and substitution reactions such as electrophilic substitutions of propargylic silanes. We report that the reaction of 3-alkynyl-2-cycloalkenones with 2 equiv of various hydridoaluminates but not hydridoborates proceeds via diastereoselective 1,4-reduction of a vinylogously propargylic intermediate alcoholate to provide exocyclic allenes as major products. Isomeric 3-alkynylcycloalkanols also are observed.",
author = "Gubbels, {Matthew A.} and Martin Hulce and Kum, {John M.} and Urick, {Andrew K.} and Eric Villa",
year = "2016",
month = "10",
day = "6",
doi = "10.1016/j.tet.2016.07.058",
language = "English (US)",
volume = "72",
pages = "6052--6063",
journal = "Tetrahedron",
issn = "0040-4020",
publisher = "Elsevier Limited",
number = "40",

}

TY - JOUR

T1 - Stereoselective synthesis of exocyclic allenes by double hydride reduction of 3-alkynyl-2-cycloalkenones

AU - Gubbels, Matthew A.

AU - Hulce, Martin

AU - Kum, John M.

AU - Urick, Andrew K.

AU - Villa, Eric

PY - 2016/10/6

Y1 - 2016/10/6

N2 - Exocyclic allene natural products and pharmaceutical agents are rare but interesting compounds: Fucoxanthin, grasshopper ketone, and analogues of prostacyclins, cephalosporins, antithrombic agents and sterol biosynthesis inhibitors are representative. Syntheses of exocyclic allenes commonly rely on extended conjugate additions to e.g., alk-2-en-4-ynones, syn SN2′-like additions to alkynyl oxiranes, and substitution reactions such as electrophilic substitutions of propargylic silanes. We report that the reaction of 3-alkynyl-2-cycloalkenones with 2 equiv of various hydridoaluminates but not hydridoborates proceeds via diastereoselective 1,4-reduction of a vinylogously propargylic intermediate alcoholate to provide exocyclic allenes as major products. Isomeric 3-alkynylcycloalkanols also are observed.

AB - Exocyclic allene natural products and pharmaceutical agents are rare but interesting compounds: Fucoxanthin, grasshopper ketone, and analogues of prostacyclins, cephalosporins, antithrombic agents and sterol biosynthesis inhibitors are representative. Syntheses of exocyclic allenes commonly rely on extended conjugate additions to e.g., alk-2-en-4-ynones, syn SN2′-like additions to alkynyl oxiranes, and substitution reactions such as electrophilic substitutions of propargylic silanes. We report that the reaction of 3-alkynyl-2-cycloalkenones with 2 equiv of various hydridoaluminates but not hydridoborates proceeds via diastereoselective 1,4-reduction of a vinylogously propargylic intermediate alcoholate to provide exocyclic allenes as major products. Isomeric 3-alkynylcycloalkanols also are observed.

UR - http://www.scopus.com/inward/record.url?scp=84986308331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986308331&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2016.07.058

DO - 10.1016/j.tet.2016.07.058

M3 - Article

AN - SCOPUS:84986308331

VL - 72

SP - 6052

EP - 6063

JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 40

ER -