Science of Synthesis

Schobert, R.; Gordon, G. J., Science of Synthesis, (2004) 27, 1033.

Wittig alkenations have been carried out with various types of phosphoranes (e.g., alkyl,[‌514‌–‌516‌] benzyl,[‌515‌–‌517‌] allyl,[‌518‌,‌519‌] methyl,[‌515‌,‌516‌] methoxycarbonylmethyl,[‌517‌] cyanomethyl,[‌516‌] or α-iodoalkyl ylides[‌516‌]) immobilized by attachment to polymer supports, such as insoluble 0.5–2% divinylbenzene cross-linked polystyrenes. The most popular, commercially available, starting compound for the synthesis of resin-bound phosphonium salts, the 2% cross-linked diphenyl(poly-4-styryl)phosphine ‌122‌, can be prepared with varying loadings (1–3 mmol phosphine·g−1 resin) and in different ways. For example, it is synthesized from 4-bromostyrene (via poly-4-bromostyrene and poly(4-lithiostyrene) or from monomeric diphenyl(4-styryl)phosphine (by suspension copolymerization with three parts of styrene and 2% divinylbenzene).[‌515‌] The direct lithiation of cross-linked polystyrene with butyllithium/N,N,N′,N′-tetramethylethylenediamine, followed by treatment with chloro(diphenyl)phosphine is also recommended.[‌517‌] Alkylation of the polymer ‌122‌ with alkyl halides gives the corresponding phosphonium salts ‌123‌, which in turn can be deprotonated to afford the respective ylides; subsequent Wittig alkenation affords alkenes ‌124‌ (‌Scheme 43‌). The solvent/base system used for the deprotonation is crucial for access to the reactive sites, and thus for the rate and completeness of ylide generation; these include sodium hydride/tetrahydrofuran, potassium tert-butoxide/tetrahydrofuran, buthyllithium/dioxane, sodium hydride/dimethylsulfoxide, sodium ethoxide/ethanol/tetrahydrofuran, and sodium hexamethyldisilazanide/tetrahydrofuran. For reactions with more highly cross-linked supports or with bulkier phosphonium salts and bases, the use of more polar solvents or the addition of small quantities of alcohols proves advantageous due to better swelling of the phosphonium ion sites. The resulting ylides are not normally isolated, but merely washed extensively to remove excess base and then reacted with the carbonyl compound straightaway. Occasionally, the immobilized precursor alkoxycarbonylphosphonium salts themselves are prepared in situ by adding bromoacetates to the polymer ‌122‌ in the presence of an aldehyde and a suitable base.[‌520‌] Immobilized reactive ylides can be reacted with aldehydes and ketones in a Z or E stereoselective manner using lithium salt free or Wittig–Schlosser protocols, respectively.[‌521‌] A phase-transfer catalyzed variant for the alkenation of aldehydes with benzyl ylides and allyl ylides, immobilized on soluble linear or insoluble 1% cross-linked polystyrene supports, is also reported.[‌519‌] Higher degrees of cross-linking (up to 20%) do not generally result in significantly better yields of alkenes or improved E/Z selectivities than those obtained under homogenous conditions.[‌522‌] The byproduct polymer-bound phosphine oxides can be reduced to phosphines with trichlorosilane and recycled. Comprehensive reviews covering the pioneering work of the 1970s, and 1980s,[‌523‌] and developments up to 2000[‌524‌] are available.

‌Meeeee 88‌ Meeeee Meeeeeeeee eeee Meeeeee-Meeee Meeeee[‌888‌–‌888‌,‌888‌,‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

M8	M8	M	M8	M8	Meeeeeeeee M	Meeeeeeeee MM	Meeee (%) ee ‌888‌	Mee
M	M	Me	(MM8)8		MMMM	MeMM8MMMe; MMM, MMMM	88	[‌888‌]
Me	M	Me	Me	Me	MMM, eeeeee, 88 e	MeMe, eeeeeee; 88°M, 8 e	88	[‌888‌]
Me	M	Me	Me	M	MMMM	MeMM8MMMe; MMM, MMMM	–e	[‌888‌]
Me	M	Me	Me	M	MMM, 88–88°M, 88 e	MeMMe, −88°M; 88°M, 8 e	88e	[‌888‌]
Me	M	Me	(MM8)8Me	M	eeeeeeeeeeeee	MM8Me8, 88% ee MeMM, Me8MM, ee, 8 e	88e	[‌888‌]
	M	Me		M	eeeeeee	MeMMe, MeMM, −88°M; ee 88 e	88e	[‌888‌]
MM8Me	M	Me	8-MMMM8M8	M	eeeeeee, 88 e, ee	88°M, 8 e, eeeeeee	88	[‌888‌]
Me	Me	M	8-MeM8M8	M	MMM, 88–88°M, 88 e	MeMMMM, ee, 8.8 e; MMM, ee, 8 e	88	[‌888‌]
MM	M	Me	8-MeMM8M8	M	MMM, 88–88°M, 88 e	MeMMMM, ee, 8.8 e; MMM, ee, 88 e	88e	[‌888‌]
M	M	M	8-MeMM8M8	M	MMM, ee, 88 e	MeMMMM, ee, 8.8 e; MMM, ee, 8 e	88e	[‌888‌]

e (M/M) 88:88.

e (M/M) 88:88.

e (M/M) eeeee eee eeeee.

e Meeee eeeeeee; 88.8% ee eee eee-eeeee eeeeee, eeeee eeeeeeeee.

e (M/M) 8:8.

e (M/M) 8:8; eeeeeee eeeeeeeeeee eeeeeeeeee.

Meeeeeeeeeee Meeeeeeee

Meeeeee ‌888‌ ee Meeeee Meeeeeee eeee Meeeeee-Meeee Meeeee; Meeeeee Meeeeeeee:[‌888‌]

Me eeeee eeeeee (8–8 eeeee) eee eeeee ee e eeeeeeeeee ee eeeeeeeeeeee eeeeeeeee 8% eeeee-eeeeee eeeeeeee(eeee-8-eeeeee)eeeeeeeee ‌888‌[‌888‌,‌888‌] (8–8 e; 8–8 eeee eeeeeeeee) ee eee MMM (88–88 eM). Mee eeeeee eee eeeeeee eeeee eeeeeeeeeee eeeeeeeeee, eeeeeeeee eee 88 e ee 88–88°M. Meeeeeeeee, eee eeeeeee eee eeeeeeeee eeeeeeee eee eeeee eeeee, eee eeeeeeeeeee eeeeee eeeeeeeeeeee eeee eee eeeeeee (88 eM), eee MM8Me8 (88 eM), eee eee Me8M (88 eM). Mee eeee ee eeeee eeeeee eee eeeee eeeee eeeeeee eeeeeeee. Meeeeeeee ee eee eeeeee eeeeeeee eee eeeeeee eee eeeeeeeee ee ee ee eee eeeee ee 8.8–8.8 eeee eeeeeeeeeee eeee eee eeee eeeeeee.

M eeeeeee eeeeeeee eeee e eeeeeeee Meeeee eeee eee eeeeeee eeee eee eeeeeee-eeeeeeeee eeeeeeeeeee eeee ‌888‌ (888 ee; 8.88–8.8 eeee eeeeeeeeeee eeee). Mee eeeeeee eee eeeeee eeeee ee eeeee eeeeeeeeee eee eeeeee eeee eee MMM (8 eM). Meeeeeee ee 8 M MeMMMM ee MMM (8.8 eM) ee ee eeeeeeee eee eeeeeeeeee ee eee eeeee eeeeee 88 eee. Meeeee eeee eee eeeeeeeee eeeeeee ee eeeeeeeee eeeeeee ee eee eeeeeee eeeee ee eeeee eeeeeee eeee eee MMM (88 eM). Meeeeeeeee, eee eeeeeee eee eeeeeeeeeee ee eee MMM (8 eM) eee eee eeeeeeee eeeeeeee (8.88–8.88 eeee) eee eeeee ee ee. Meeeeeeee ee MM eeeeeeee eee eeeeeeeeee eeeeeeee eee eeeeeeeee eeeeeeee eeeeee 88–88 eee (eeeeeeeeee >88%). Mee eeeeee-eeeeeeeeee eeee eee eeeeeeeee, eeeeeeee eeee eeeeeeeeee eeeeeee eeeeeeee (88 eM ee eee MMM), eee eeeeeeee eeeeeee e eeeee eeeeee ee eeeeee eee (8.8–8.8 e). Meeeeeeeeee ee eee eeeeeeee eeeee eeeeeee eeeeeeee eeee eee eeeee eeeeee.

References