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. 2009 May 13;131(18):6516-24.
doi: 10.1021/ja900147s.

Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones

Mahmud M Hussain  1 , Hongmei Li, Nusrah Hussain, Mercedes Ureña, Patrick J Carroll, Patrick J Walsh
Affiliations

Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones

Mahmud M Hussain et al. J Am Chem Soc. .

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.

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Figures

Figure 1
Figure 1
Proposed Transition State for Diastereoselective Cyclopropanation of B(pin) Substituted Allylic Alkoxides
Figure 2
Figure 2
Optimized Conditions for Synthesis of 2,3-Disubstituted Cyclobutanones via Ring Expansion
Figure 3
Figure 3
Synthesis of quercus lactones A and B
Scheme 1
Scheme 1
Challenges in the Generation and Reactions of 1-Alkenyl-1,1-bimetallics
Scheme 2
Scheme 2
Generation and Reactions of 1-Alkenyl-1,1-bimetallics
Scheme 3
Scheme 3
Tandem Carbonyl Addition/Alkoxide-directed Cyclopropanation
Scheme 4
Scheme 4
Kulinkovich Reaction to Form Trisubstituted Cyclopropanols
Scheme 5
Scheme 5
Pinacol-type Rearrangement of a-Hydroxycyclopropyl Carbinols
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