The Chan rearrangement is a

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

that involves rearranging an acyloxy acetate (1) in the presence of a strong base to a 2-hydroxy-3-keto-ester (2). This procedure was employed in the Holton Taxol total synthesis.

Reaction mechanism

The

methylene bridge In organic chemistry, a methylene bridge, methylene spacer, or methanediyl group is any part of a molecule with formula ; namely, a carbon atom bound to two hydrogen atoms and connected by single bonds to two other distinct atoms in the rest of t ...

in the reactant with adjacent

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...

and acetyl substituents is acidic and can be

deprotonated Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...

by strong non-nucleophilic bases such as

lithium tetramethylpiperidide Lithium tetramethylpiperidide (often abbreviated LiTMP or LTMP) is a chemical compound with the molecular formula . It is used as a non-nucleophilic base, being comparable to LiHMDS in terms of steric hindrance. Synthesis It is synthesised by the ...

lithium diisopropylamide Lithium diisopropylamide (commonly abbreviated LDA) is a chemical compound with the molecular formula . It is used as a strong base and has been widely utilized due to its good solubility in non-polar organic solvents and non-nucleophilic nature ...

(LDA) as in an

aldol reaction The aldol reaction is a means of forming carbon–carbon bonds in organic chemistry. Discovered independently by the Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in 1872, the reaction combines two c ...

. The thus formed

enolate In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl () compounds. Rarely isolated, they are widely used as reagents in the synthesis of organic compounds. Bonding and structure Enolate anions are electr ...

then gives a

nucleophilic acyl substitution Nucleophilic acyl substitution describe a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl deriv ...

with the adjacent

of the acetyl group through a short lived intermediate

oxirane Ethylene oxide is an organic compound with the formula . It is a cyclic ether and the simplest epoxide: a three-membered ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless and flammable gas with a faintly swe ...

. Acidic workup liberates the free hydroxyl group.

References

# ''Rearrangement of α-acyloxyacetates into 2-hydroxy-3-ketoesters'' S. D. Lee, T. H. Chan, and K. S. Kwon '' Tetrahedron Lett.'' 1984, ''25'', 3399-3402. () # ''First total synthesis of taxol 1.'' Functionalization of the B ring Robert A. Holton, Carmen Somoza, Hyeong Baik Kim, Feng Liang, Ronald J. Biediger, P. Douglas Boatman, Mitsuru Shindo, Chase C. Smith, Soekchan Kim, et al.; ''

J. Am. Chem. Soc. The ''Journal of the American Chemical Society'' is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the ''Journal of Analytic ...

'' 1994, ''116(4)'', 1597-1598. ({{doi, 10.1021/ja00083a066)

Reaction mechanism

References

See also