Science of Synthesis

Schobert, R.; Gordon, G. J., Science of Synthesis, (2004) 27, 1019.

The Z-selective Wittig alkenation of an aldehyde is normally carried out by adding it to a chilled solution of an unstabilized ylide in an aprotic solvent, such as hexane, benzene, toluene, tetrahydrofuran, dioxane, dimethylformamide, or hexamethylphosphoric triamide. The solution is then quickly warmed to room temperature and stirred until the completion of the reaction (this is normally indicated by the disappearance of the typical orange-red color). Gentle heating may be required in some cases. The ylide solution is customarily prepared in situ at room temperature or above by treating a slurry of the phosphonium salt in one of the solvents listed above with a non-lithium base such as sodium hydride, sodium amide,[‌137‌] or preferably sodium hexamethyldisilazanide,[‌311‌] which is soluble even in warm hexane. Removal of the residual phosphonium and the inorganic sodium salts is possible by filtration under a protective gas atmosphere, but is not normally necessary. Ammonia and hexamethyldisilazane are volatile byproducts and can be removed by evaporation of the (filtered) ylide solution under reduced pressure and redissolution of the residue in an appropriate absolute solvent. Separation of the product alkene and phosphine oxide is usually achieved by crystallizing (“freezing out”) most of the latter from hexane at −20°C, and removing the rest by column chromatography on silica gel (hexane/diethyl ether 3:1 or neat dichloromethane as eluents). The two-step procedure is illustrated in ‌Scheme 33‌, which refers to the syntheses of some representative alkenes ‌93‌.[‌17‌,‌311‌,‌473‌–‌477‌] Ylides bearing polar amino or carboxylic acid groups bonded to P-aryl residues have also been developed; these give easily removable water-soluble phosphine oxides.[‌477‌] The E/Z ratio of alkene isomers produced is best established by gas chromatography or high-pressure liquid chromatography. E-Selective alkenation of aldehydes is usually achieved by reactions with preformed isolated stabilized ylides in a wide range of solvents, including protic ones and water, at elevated temperatures.[‌187‌] Reaction rates and E-selectivities may be increased by catalytic additives such as benzoic acid or lithium salts.[‌478‌]

MMMMMM: Meeeeeeeeeeeeeeeeeee eeeeeeee (MMMM) ee e eeeeeeee eeeee eeeeeeeeee eee ee eee eee eeee eeeeeeee. Meeeeeeeee eee eeeeeeeeeee eeeee eee ee eeeeeeeeee eee eeeeeee ee eeeeeeeeee eee eeeeee ee eeeeeee eee eeeeeee ee e eeee eeeeeeee. Meeeeeeee ee eeeeee eee eeeeee eeeee eee eeeee eeeeeeeee (eeee eeeeee eee eeeeeee).

‌Meeeee 88‌ M-Meeeeee eeee Meeeeeeee eee Meeeeeeeeeee Meeeeeeeee Meeeee[‌88‌,‌888‌,‌888‌–‌888‌]

‌Meeeeeeeeee 88‌

M8	M8	Meee	Meeeeeeeee ee Meee 8	Meeee (M/M)	Meeee (%)	Mee
Me	(MM8)8MMe	MeMMMMe	MMM, −88°M	88:8	88	[‌888‌]
Me	(MM8)8MMe	MeMMMMe	MMM, 88°M	88:8	88	[‌888‌]
(MM8)8Me		MeMMMMe	MMM, −88°M	88:8e	88	[‌888‌]
Me		MeMMMMe	MMM, −88°M	–e	88	[‌888‌]
Me		MeMM8e	eeeeeee, −88°M	88:8	88	[‌888‌]
	(MM8)8MM8Me	MMMMMe	MMM, −88°M	–e	88	[‌888‌]
		MeMMMMe	MMM/MMMM, −88°M	88:8	88	[‌888‌]
		MeMMMMe	MMM, −88°M	–e	88	[‌88‌]

e Meeee eeeeeeeee ee MMM, ee, 88 eee, ee eeeeee, 8 e.

e Meee eeeee: 8% ee eee M,M-eeeeee.

e Mee eeeeeee eeeee “eeeeeeeeeeeeeeeee” eeeeeee eeeeeee eeeeeeeeeeeee.

e Meeeeeeeee ee eee eeee 8.

e Meeee eeeeeeeee ee MMM/MMMM, 8°M, 8 e.

Meeeeeeeeeee Meeeeeeee

(M)-Meeee-8-eeee Meeeeee [‌88‌, M8 = Me; M8 = (MM8)8MMe]; Meeeeee Meeeeeeee:[‌888‌]

Meeeee(eeeeeeeee)eeeeeeeeeee eeeeeee (8.88 e, 88.8 eeee) eee eeeeeeeee ee eeeee MMM (88 eM) eeeee ee eeeeeeeeee ee eee M8 eee eeeeeee ee eeee eeee MeMMMM (8.88 e, 88.8 eeee) ee eeeee MMM (88 eM). Mee eeeeeee eee eeeeeee eeeee ee ee eee 88 eee, eeee eeeee eeeeee eeeeee eee eeeeeee eeee. Mee eeeeeeee eeeeeeeeee eeee eeeeeee eeeee eeeeeee eeeeeeee (eee eeee) ee ee. 88°M, eee eeeeeee eee eeeeeeeeeee ee eeeee MMM (88 eM), eee eee eeee eeeeeee ee −88°M (eee eee/eeeeeee eeee). 8-Meeeeeee eeeeeee (8.88 e, 88.8 eeee) ee eeeee MMM (88 eM) eee eeeeee eeeee, eeeeeeeee eee eeee eee eeeee ee eee eeeee eeee eeeeeeeee eeeeeeeeee eee eeeeeeeeee eeeee. Mee eeeeeee eee eeee ee −88°M eee 8 e, eee eeee eeeeeee eeeeee ee ee ee eeeee ee e eee eeeee eeee, eee eeee eeee eeeeeeee eee e eeeeeee 88 e. Mee eeeeeee eee eeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeeeee eeeee eee eeeeeeeee eeeeeeeeee eeee eeeeee (888 eM). Mee eeeeeeee eeeeeeee eeee eeeeeeee, eeeeee eeee eee. ee MeMMM8 eeee (88 eM) eeeeeeee ee M8M (88 eM), eee eeee eeeee (MeMM8). Meeeeeee Me8MM eee eeeeeee eeeeee ee eeeeeeee eeeeeeeeeeeeeee ee −88°M ee ee eeeeee eeeeeeeeeeeeee [eeeeee eee 88 (88 e), Me8M/eeeeeee 8:8]. Meeeeeeeeeee ee eee eeeee eeeeeee eeee e eeeeeeeee eee; eeeee: 8.88 e (88%); ee 888–888°M/8.88 Meee; (M/M) 88:8 (MM, MMMM eeeeee, 888°M).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8, 888.
• 8.Meeeee-Meee, (8888) M 8, 888.
• 8.Meeeee-Meee, (8888) M 8, 888.
• 8.Meeeee-Meee, (8888) M 88e, 888.