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 M. Villa

doi:10.1016/j.tet.2016.07.058

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 M. Villa

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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 S_N2′-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 language	English (US)
Pages (from-to)	6052-6063
Number of pages	12
Journal	Tetrahedron
Volume	72
Issue number	40
DOIs	https://doi.org/10.1016/j.tet.2016.07.058
State	Published - 2016

All Science Journal Classification (ASJC) codes

Biochemistry
Drug Discovery
Organic Chemistry

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@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 Villa, {Eric M.}",

note = "Funding Information: This work was supported by the Creighton University President's Faculty Research Fund , grant number 240039-204000 . ",

year = "2016",

doi = "10.1016/j.tet.2016.07.058",

language = "English (US)",

volume = "72",

pages = "6052--6063",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier Limited",

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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 M.

N1 - Funding Information: This work was supported by the Creighton University President's Faculty Research Fund , grant number 240039-204000 .

PY - 2016

Y1 - 2016

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.

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JO - Tetrahedron

JF - Tetrahedron

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