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Updated: Jul 18, 2025
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Cp2TiCl-Promoted Endo-Trig Radical Cyclization to Six- and Seven-Membered Carbocycles: Synthesis of (±)-Isoclavukerin
Sabnam Begum1, Rajarshi Bhattacharya1, Shashwati Paul1
1Department of Organic Chemistry, Indian Institute of Science, Bengaluru 560012, India.
Abstract:
A systematic study is undertaken to investigate the less explored endo-trig radical cyclization in activated olefin-appended epoxides using Cp2TiCl. The radical generated by the Ti(III)-promoted reductive opening of the epoxy ring promptly underwent endo-trig cyclization, giving access to differently 1,3-disubstituted six- and seven-membered carbocycles in good yields and diastereoselectivity. This protocol was successfully employed in the construction of 5,7- and 6,7-fused bicyclic frameworks entailing a de novo synthesis of (±)-isoclavukerin A belonging to tri-nor-guaiane class of sesquiterpene natural products in eight simple steps from commercially available starting materials. Besides the Ti(III)-mediated reaction serving as a key step in the synthesis, a sequential [2,3]-sigmatropic rearrangement/syn-elimination of an allyl sulfenate intermediate successfully rendered the highly constrained diene moiety in the hydroazulene core of the target molecule.
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