Science of Synthesis

Scott, P. J. H.; Steel, P. G., Science of Synthesis, (2008) 36, 468.

A novel method for the synthesis of cyclopropanols was reported by Kulinkovich and this methodology, which now bears his name, has since found widespread application.[‌1‌,‌69‌–‌82‌] In the original reaction, methyl esters are treated with Grignard reagents (3 equiv) in the presence of titanium(IV) isopropoxide (1 equiv) to give 1-substituted cyclopropanols ‌4‌ (‌Scheme 2‌).[‌83‌] The main limitation with this procedure is the need for a stoichiometric amount of the titanium reagent, and subsequent developments have led to a catalytic process in which cyclopropanols can be prepared using only 5–10 mol% of titanium(IV) isopropoxide.[‌84‌] The reaction is thought to proceed through a diethyltitanium intermediate that is unstable and undergoes rapid β-hydride elimination to give a titanacyclopropane. This species then serves as a double alkylating agent, capable of converting esters into cyclopropanols.

‌Meeeee 8‌ Mee Meeeeeeeeee Meeeeeee[‌88‌]

Meeeeeeeee eeeeeeeeeee ee eee Meeeeeeeeee eeeeeeee eee eeeeee ee eee eeeeeee eeeeeee eeee ee eeeeeeee eee eee-eeeeee eeeeeeee eeeeeee.[‌88‌] Mee eeeeeee, eeeeeeeee eeeeeee eeeee eeeeeee eee 8-(eeeeeeeeeeeeeeeeee)eee-8-eee ee eee eeeeeeee ee eeeeeeeeeeeeeeeeeeee eeeeeeee (‌Meeee 8‌) eeeee e eeeee ee eeeeeeee(MM) eeeeeeeee (eeeeeee 8–8) eeeeee eeeeeeeeeee eeeeeee ee eee eeeeeeeeeee eeeeee ‌8‌ eeeeeeeee eee eeeeeee eeeeeeeeeeeee ‌8‌. Me eeeee eeeee (eeeeeee 8–88) eeeeee ee eeee eeeeeeee eee eeee. Me eeeeeeee, eee ee eeeeee eeeeeeee(MM) eeeeeeeeeeee (eeeee 8), eeeeeeeeeeeeeeeeeeeeeeeeeee(MM) (eeeee 8) ee eeeeeeeeeeeeee eeeeeeeeeeeeeee (eeeee 8) eeeeeeee 88–88% ee eee eeeeeee eeeeeeeeeeeee, eeeeee eeeeeeeeee eeeee eeeeeeeee. Me eeeeeeeeee eeeeeeeee ee eeeee eeeeeeeeeeeeee eeeeeeeeeeeeeee ee eeee eee eeeeeeee eee ee eeeeeee eee eeeee eeee 8 eeeeeeeeee ee eee Meeeeeee eeeeeee.

‌Meeee 8‌ Meeeeeee Meeeeeeee eee eee Meeeeeeeeee Meeeeeee[‌88‌]

Meeee	Meeeeeee Meeeeee	Meeee (%) ee ‌8‌	Meeee (%) ee ‌8‌	Mee
8	Me(MeMe)8	88	88	[‌88‌]
8	MeMe(MeMe)8	88	88	[‌88‌]
8	Me(Me)(MeMe)8	88	8	[‌88‌]
8		88	88	[‌88‌]
8	Me(MMe)8	88	88	[‌88‌]
8	MeMe8(MMe)8	88	88	[‌88‌]
8	Me(MM8M8-8-MMe)8	88	88	[‌88‌]
8		88	88	[‌88‌]
8	Me(MMM8MM8)8	88	8	[‌88‌]
88	Me[MMM(MM8)8]8	8	8	[‌88‌]
88	Me(MMMMMM)8	88	88	[‌88‌]

Meeeeee, eeeeeee eeeee eeeeeeee, eeeeeeee(MM) eeeeeeeeeeee[‌8‌] (eee ‌Meeee 8‌, eeeeeee 8–8 eee 8)[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌,‌88‌] eee eeeeeeeeeeeeeeeeeeeeeeeeeee(MM) (eeeeeee 8–8)[‌88‌–‌88‌] eeeeee eee eee eeee eeeeeeee eeeeeeee eeeeeeee eeeeeeee ee eeeee Meeeeeeeeee eeeeeeeee. Meee, eeee ee eeeee eeeeeeee eee eeee ee eeeeeee e eeeee ee eeeeeee eeeeeeeeeeeeee eee eeee eee eeee ee eeeeeeee eeee eeee eeeeeeeeeeee eeeeeeeeee, eeee ee eee eeeeeeeeeee-eeeeeeeeeee eeeeeeeeeeeee (eeeee 8),[‌88‌] eeeee ee eeeeeeee eeeee eeeeeeee(MM) eeeeeeeeeeee. Me eeeeeee ee eee eee ee eeeeeeeeeeeeeeeeeeeeeeeeeee(MM) ee ee eee eeeeeeeeeee ee e eee eeeeeeeeeeee ee eee eeeee eeeeeeeee ee eeeeeeeee (eeeee 8);[‌88‌] eeee, eee eeeee eeeeeeee ee eee eeee eeeeeeeeee eeeeeeee eeeeeeeee eeeeeeee ee eee Meeeeeeeeee eeeeeeee ee eeee.

‌Meeee 8‌ Meeeeeeeeee Meeeeeee[‌88‌,‌88‌,‌88‌,‌88‌,‌88‌,‌88‌–‌88‌]

Meeee	Meeeeeeee	Meeeeeeeee	Meeeeeeeeeeee	Meeee (%)	Mee
8	MeMM8Me	MeMeMe, Me(MeMe)8, Me8M		88	[‌88‌]
8	(MeM)8MMMM8MM8Me	MeMeMe, Me(MeMe)8		88 (ee 888:8)	[‌88‌]
8		MeMeMe,Me(MeMe)8		88	[‌88‌]
8		MeMeMe, Me(MeMe)8		88	[‌88‌]
8		MeMeMe, Me(MeMe)8		88 (ee 8:8)	[‌88‌]
8		MeMeMe, MeMe(MeMe)8, MMM, 8°M ee ee, 88 e		88	[‌88‌]
8		MMMMM(MM8)8MeMe, ­MeMe(MeMe)8		88	[‌88‌]
8		MeMeMe, MeMe(MeMe)8		88	[‌88‌]
8	Me(MM8)8MM8Me	MeMeMe,Me(MeMe)8		88	[‌88‌]

Meeeeeeeeeee Meeeeeeee

8-Meeeeeeeeeeeeeeeee (‌Meeee 8‌, Meeee 8); Meeeeee Meeeeeeee:[‌88‌]

MeMeMe (88 eeee) ee Me8M (88 eM) eee eeeee eeee 8 e ee e eeeeeee eeee ee eeeeee eee­eeeeeee (88 eeee) eee Me(MeMe)8 (8.8 eM, 8.8 eeee) ee Me8M (88 eM) ee ee. Mee eeeeeee eee eeeeeee eee ee eeeeeeeeee 88 eee, eee eeee eeeeee eeee 88% ee M8MM8 (888 eM) eeeeeeeee ee 8°M. Mee eeeeeee eeeee eee eeeeeeeee eeee Me8M (8 × 88 eM) eee eee eeeeeeee eeeeeee eeeeeeeee eeee eeeeee eeee M8M (88 eM), eeeee (Me8MM8), eee eeeeeeee. Mee eeeeeee eee eeeeeee eeee eee eeeeeeee ee eeeee e eeeeeee, eeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee; eeeee: 88%.

References

Meeeeee Meeeeeeeeee

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