Chan rearrangement
The Chan rearrangement is a chemical reaction discovered by Tak-Hang Chan . It is a rearrangement reaction from an acyloxacetate to a 2-hydroxy-3-ketoester.
Overview reaction
In the Chan rearrangement, an acyloxacetate is rearranged in the presence of a strong base , here lithium diisopropylamide (LDA), to form a 2-hydroxy-3-ketoester:
The residues are organic residues. The reaction was successfully used in the total synthesis of paclitaxel ( Taxol ) by Robert A. Holton.
Reaction mechanism
The reaction mechanism of the Chan rearrangement is as follows:
The methylene group of acyloxacetate ( 1 ), here marked in blue , is so acidic that it can be deprotonated with strong but not nucleophilic bases such as lithium diisopropylamide (LDA). As a result of the deprotonation , the carbanion 2 is formed . The nucleophilic attack of the generated anion on the neighboring acyl group leads to an intermediate epoxide 3 . The migration of electrons creates an alcoholate 4 from the epoxide with ring opening . The acidic work-up ultimately leads to a hydroxyl group and the product 2-hydroxy-3-ketoester 5 is formed . The reaction is related to the Darzens glycidic ester synthesis .
Individual evidence
- ↑ SD Lee, TH Chan, KS Kwon: Rearrangement of α-acyloxyacetates into 2-hydroxy-3-ketoesters. In: Tetrahedron Letters. 25, No. 32, 1984, pp. 3399-3402, doi : 10.1016 / S0040-4039 (01) 91030-5 .
- ^ Robert A. Holton, Carmen Somoza, Hyeong Baik Kim, Feng Liang, Ronald J. Biediger, P. Douglas Boatman, Mitsuru Shindo, Chase C. Smith, Soekchan Kim: First total synthesis of taxol. 1. Functionalization of the ring. In: Journal of the American Chemical Society. 116, No. 4, 1994, pp. 1597-1598, doi : 10.1021 / ja00083a066 .
- ↑ Z. Wang (Ed.): Comprehensive Organic Name Reactions and Reagents, 3 Volume Set . John Wiley & Sons, Hoboken, New Jersey 2009, ISBN 978-0-471-70450-8 , p. 624.