The reaction proceeds by three major steps: (1) the rapid protonation of oxygen, (2) the slow,rate-determining step comprising the1,3-shift of the protonated hydroxy group, and (3) theketo-enol tautomerism followed by rapid deprotonation.[5] Formation of the unsaturated carbonyl compound is irreversible.[6] Solvent is important andsolvent caging is proposed to stabilize thetransition state.[7]
The reaction of tertiary alcohols containing an α-acetylenic group does not produce the expected aldehydes, but rather α,β-unsaturatedmethyl ketones via anenyneintermediate.[8][9] This alternate reaction is called theRupe reaction, and competes with the Meyer–Schuster rearrangement in the case of tertiary alcohols.
The Rupe rearrangementMechanism of the Rupe rearrangement
The traditional Meyer–Schuster rearrangement is induced by strong acids, which introduces competition with the Rupe reaction if the alcohol is tertiary.[1] Milder conditions are possible withtransition metal-based andLewis acid catalysts (for example, Ru-[10] and Ag-based[11] catalysts).Microwave-radiation withInCl3 catalyst to give excellent yields with short reaction times and goodstereoselectivity.[12]
The Meyer–Schuster rearrangement has been used in several syntheses. ω-Alkynyl-ω-carbinollactams convert into enamides using catalytic PTSA[13] α,β-Uunsaturatedthioesters have been prepared from γ-sulfur substituted propargyl alcohols.[14] 3-Alkynyl-3-hydroxyl-1H-isoindoles rearrange under mildly acidic conditions to theα,β-unsaturated carbonyl compounds.[15] The synthesis of a part ofpaclitaxel exploits this rearrangement for adiastereomerically-selective route to theE-alkene.[16]
Part of the synthesis of taxol using the Meyer-Schuster rearrangement
The step shown above had a 70% yield (91% when the byproduct was converted to the Meyer-Schuster product in another step). The authors used the Meyer–Schuster rearrangement because they wanted to convert a hindered ketone to an alkene without destroying the rest of their molecule.
^Chihab-Eddine, Abderrahim; Jilale, Abderrahim; Daïch, Adam; Decroix, Bernard (2000). "Reactivity ofN -benzyl-3-nitrophthalimide: A facile access to isoindolo[1,2-d ][3,5]benzothiazocine derivatives".Journal of Heterocyclic Chemistry.37 (6):1543–1548.doi:10.1002/jhet.5570370622.)
^Yoshimatsu, Mitsuhiro; Naito, Motoyo; Kawahigashi, Masataka; Shimizu, Hiroshi; Kataoka, Tadashi (1995). "Meyer-Schuster Rearrangement of .gamma.-Sulfur-Substituted Propargyl Alcohols: A Convenient Synthesis of .alpha.,.beta.-Unsaturated Thioesters".The Journal of Organic Chemistry.60 (15):4798–4802.doi:10.1021/jo00120a024.)
^Omar, Enouri A.; Tu, Chi; Wigal, Carl T.; Braun, Loren L. (1992). "The meyer-schuster rearrangement and hydrohalide addition of 3-alkynyl-3-hydroxy-1H -isoindol-1-ones".Journal of Heterocyclic Chemistry.29 (4):947–951.doi:10.1002/jhet.5570290445.)
^Crich, David; Natarajan, Swaminathan; Crich, Joyce Z. (1997). "Synthesis of the taxol AB-system by olefination of an A-ring C1 ketone and direct B-ring closure".Tetrahedron.53 (21):7139–7158.doi:10.1016/S0040-4020(97)00411-0.)
^Meyer, Kurt H.; Schuster, Kurt (1922). "Umlagerung tertiärer Äthinyl-carbinole in ungesättigte Ketone".Berichte der Deutschen Chemischen Gesellschaft (A and B Series).55 (4):819–823.doi:10.1002/cber.19220550403.)
