Tags

Type your tag names separated by a space and hit enter

Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones.
J Am Chem Soc. 2009 May 13; 131(18):6516-24.JA

Abstract

1-Alkenyl-1,1-heterobimetallics are potentially very useful in stereoselective organic synthesis but are relatively unexplored. Introduced herein is a practical application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of versatile cyclopropyl alcohol boronate esters, which are valuable building blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ transmetalation with dialkylzinc reagents furnishes 1-alkenyl-1,1-borozinc heterobimetallic intermediates. Addition of the more reactive ZnC bond to aldehydes generates the key B(pin) substituted allylic alkoxide intermediates. An in situ alkoxide directed cyclopropanation proceeds with the formation of two more CC bonds, affording cyclopropyl alcohol boronate esters with three new stereocenters in 58-89% isolated yields and excellent diastereoselectivities (>15:1 dr). Oxidation of the BC bond provides trisubstituted alpha-hydroxycyclopropyl carbinols as single diastereomers in good to excellent yields (75-93%). Facile pinacol-type rearrangement of the alpha-hydroxycyclopropyl carbinols provides access to both cis- and trans-2,3-disubstituted cyclobutanones with high stereoselectivity (>17:1 dr in most cases) from a common starting material. This methodology has been applied in the synthesis of quercus lactones A and B.

Links

PMC Free PDF
PMC Free Full Text

Authors+Show Affiliations

Hussain MM
P. Roy and Diana T. Vagelos Laboratories, University of Pennsylvania, Department of Chemistry, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
Li H
No affiliation info available
Hussain N
No affiliation info available
Ureña M
No affiliation info available
Carroll PJ
No affiliation info available
Walsh PJ
No affiliation info available

MeSH

Boronic AcidsButanonesCyclobutanesEthers, CyclicOrganic Chemistry PhenomenaStereoisomerismZinc

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

19382808

Citation

Hussain, Mahmud M., et al. "Applications of 1-alkenyl-1,1-heterobimetallics in the Stereoselective Synthesis of Cyclopropylboronate Esters, Trisubstituted Cyclopropanols and 2,3-disubstituted Cyclobutanones." Journal of the American Chemical Society, vol. 131, no. 18, 2009, pp. 6516-24.
Hussain MM, Li H, Hussain N, et al. Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones. J Am Chem Soc. 2009;131(18):6516-24.
Hussain, M. M., Li, H., Hussain, N., Ureña, M., Carroll, P. J., & Walsh, P. J. (2009). Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones. Journal of the American Chemical Society, 131(18), 6516-24. https://doi.org/10.1021/ja900147s
Hussain MM, et al. Applications of 1-alkenyl-1,1-heterobimetallics in the Stereoselective Synthesis of Cyclopropylboronate Esters, Trisubstituted Cyclopropanols and 2,3-disubstituted Cyclobutanones. J Am Chem Soc. 2009 May 13;131(18):6516-24. PubMed PMID: 19382808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones. AU - Hussain,Mahmud M, AU - Li,Hongmei, AU - Hussain,Nusrah, AU - Ureña,Mercedes, AU - Carroll,Patrick J, AU - Walsh,Patrick J, PY - 2009/4/23/entrez PY - 2009/4/23/pubmed PY - 2009/7/28/medline SP - 6516 EP - 24 JF - Journal of the American Chemical Society JO - J Am Chem Soc VL - 131 IS - 18 N2 - 1-Alkenyl-1,1-heterobimetallics are potentially very useful in stereoselective organic synthesis but are relatively unexplored. Introduced herein is a practical application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of versatile cyclopropyl alcohol boronate esters, which are valuable building blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In situ transmetalation with dialkylzinc reagents furnishes 1-alkenyl-1,1-borozinc heterobimetallic intermediates. Addition of the more reactive ZnC bond to aldehydes generates the key B(pin) substituted allylic alkoxide intermediates. An in situ alkoxide directed cyclopropanation proceeds with the formation of two more CC bonds, affording cyclopropyl alcohol boronate esters with three new stereocenters in 58-89% isolated yields and excellent diastereoselectivities (>15:1 dr). Oxidation of the BC bond provides trisubstituted alpha-hydroxycyclopropyl carbinols as single diastereomers in good to excellent yields (75-93%). Facile pinacol-type rearrangement of the alpha-hydroxycyclopropyl carbinols provides access to both cis- and trans-2,3-disubstituted cyclobutanones with high stereoselectivity (>17:1 dr in most cases) from a common starting material. This methodology has been applied in the synthesis of quercus lactones A and B. SN - 1520-5126 UR - https://www.unboundmedicine.com/medline/citation/19382808/Applications_of_1_alkenyl_11_heterobimetallics_in_the_stereoselective_synthesis_of_cyclopropylboronate_esters_trisubstituted_cyclopropanols_and_23_disubstituted_cyclobutanones_ L2 - https://doi.org/10.1021/ja900147s DB - PRIME DP - Unbound Medicine ER -