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Please login to access the full content or check if you have access via Variation 3: Synthesis with Unsymmetrical Phosphorus Ylides and Unsymmetrical Ketones

DOI: 10.1055/sos-SD-047-00004

Schobert, R.; Hölzel, C.; Barnickel, B.Science of Synthesis, (20104758.

Alkenations of unsymmetrical carbonyl compounds furnishing mixtures of E- and Z-isomers that deviate significantly from 1:1 are known with stabilized and unstabilized (i.e., reactive) phosphorus reagents. Without distinct built-in stereocontrol, this bias for the Z- or the E-isomer usually originates from differences in steric bulk of substitutents on the carbonyl component. For example, the Wittig reaction of methyl 2-(triphenylphosphoranylidene)propanoate (122)[‌430‌,‌431‌] with acetaldehyde furnishes a 97:3 mixture of methyl (2E)-2-methylbut-2-enoate [(E)-124] and methyl (2Z)-2-methylbut-2-enoate [(Z)-124], respectively in 90% overall yield (Scheme 43).[‌432‌] The reason is the stability of the starting ylide 122, which permits the reversible formation of the intermediate betaines and the accumulation of the more stable threo-betaine 123A. In contrast, reaction of the more reactive ethylidenetriphenylphosphorane with methyl pyruvate leads to a 68:32 mixture of methyl (2E)-2-methylbut-2-enoate and methyl (2Z)-2-methylbut-2-enoate, respectively. Likewise, the HornerEmmons reaction between 6-acetoxy-4-methylhex-4-enal (126) and sodium 1-(diethoxyphosphoryl)-1-(ethoxycarbonyl)ethanide (125) in tetrahydrofuran at 0°C gives a 73% yield of the acetoxy ester 127 with an E,E/Z,E isomer ratio of 88:12 (Scheme 43).[‌433‌]

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