Science of Synthesis

Fusano, A.; Ryu, I., Science of Synthesis: Multicomponent Reactions, (2014) 2, 411.

Unsymmetrical ketones ‌5‌ can be synthesized by the formal double alkylation of carbon monoxide,[‌22‌] where the three-component coupling of an alkyl iodide, carbon monoxide, and an electron-deficient alkene is carried out using tributyltin hydride as a radical chain mediator (‌Scheme 4‌). Performing the reaction under high-dilution conditions proves to be a very effective way to increase the relative concentration of carbon monoxide relative to tributyltin hydride in this three-component reaction. The use of a slower radical mediator, tris(trimethylsilyl)silane (TTMSS), has subsequently been proven to be superior to tributyltin hydride for this type of reaction, since the process can be conducted using a nearly equimolar amount of the alkene along with much lower carbon monoxide pressures.[‌23‌] The use of supercritical carbon dioxide has also been successfully examined.[‌24‌]

‌Meeeee 8‌ Meeeee Meeeeeeee ee Meeee-Meeeeeeee Meeeeeee Meeeeeee ee Mee Meeeeeee ee Meeeeee[‌88‌,‌88‌]

‌Meeeeeeeeee 8‌

e Meeee ee eeeeeeee eeeeeee eeeee eeeeeeeeeeee.

Meeeee eeee eee eeeee eeee eee eee ee eeeeeeeeeeeeeeeeee eeeeeeeeeeeeeeee ee e eeeeeeee eeeeee eeee eeeee eeee ee eeeeee eeeeeeeeeeeee eeeeeee ‌8‌ ee eeeeeeee ee ee eeeee eeeeee eeee eeeeee eeeeeeee (88 eee) eee ee eeeeeeee-eeeeeeeee eeeeee (8.8–8.8 eeeee) ee e eeeeeeeeeeeee ee 8.888 M ee eeeeeee ee eeeeeeee eeeeeeeeeee (‌Meeeee 8‌).[‌88‌]

‌Meeeee 8‌ Meeeee Meeeeeeee ee Meeee-Meeeeeeee Meeeeeee Meeeeeee ee Meeeeeeeeeeeeeeeee Meeeeeeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 8‌

e Meeee ee eeeeeeee eeeeeee eeeee eeeeeeeeeeee.

e Meeeeeee eee eeee ee eee eeeeeee.

Me e eee eeeeeee eeeeeeee eeeeeee eeeeeeeeeeeee eeeeeeee, 8-eee eeeeeeeeeee ee ee eeee eeeeeee eeeeeeeee eeee ee eee-8-eeee eeeeee eee eeeeee eeeeeeee eee eeeeeeee ee eeeeeee eeeee eeeeeeeeeeeeeee.[‌88‌] M eeee-eeeeeee eee-eeeeeeee eeeeeeeee ee eeee eeee ee eeeeeeee eeeee eeeeeee eeeeeee,[‌88‌] eee eee eeeeeee eeeee-eeeeeeeee eeeeeeee eeeeeeeeeee ee ‌Meeeee 8‌ eee ee eeeeeeeee ee eeee eeeeeeeeeeeeeee ‌8‌ ee eeeeeeee eeee eeee ee eeeeee eeeeeeee.[‌88‌] Meeeeeeeeeeee eeeeeeeeeeeeeeee ee eeee eeeeeeee eee e eeee(eeeeeeeeeeeeee)eeeeee-eeeeeeee [e + 8]-eeeeeeeeeeeeeeee eeeeeeee ee eeee eeeeeeee.[‌88‌]

‌Meeeee 8‌ Meeeeeeeeeeeee Meeeeeeee ee Meeee-Meeeeeeee Meeeeeee Meeeeeee ee Meeee-Meeeeee Mee-Meeeeeee Meeeeeeee[‌88‌]

‌Meeeeeeeeee 8‌

Meeeeeeeeeee Meeeeeeee

Meeeeeeeeeeee Meeeeee ‌8‌; Meeeeee Meeeeeeee Meeee Meeeeeeeeee Meeeeee:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M eeeeeee ee eeeeeee (88 eM) (MMMMMMM: eeeeeeeeee), eee eeeee eeeeee (8.88 eeee), Me8MeM (8.88 eeee), MMMM (8.8 eeee), eee eee eeeeee (8.8 eeee) eee eeeeee ee e 888-eM eeeeeeeee eeeee eeeeeeeee eeeee eeee e eeeee-eeeeeeee eeeee eeee. Mee eeeeeeeee eee eeee eeeeeeeeeee eeee MM (88 eee) eee eeeeee eeee eeeeeeee ee 88 °M eee 8 e. Mee eeeeee MM eee eeeeeeeeee ee ee eee eeee eee eeeeeee eee eeeeeee ee e eeeeee eeeeeeeeee. Mee eeeeeee eee eeeeeeeee ee Me8M (8 eM) eee eeee eeeeeeee eeee eee eeeeeee eeee eee. ee MM. Mee Me8MeM eeeeeeeeeee eeeeeeee eee eeeeeee ee eeeeee eeeeeeeeee, eee eee eeeee eee eeeeee eeee Me8M (8 × 8 eM). Mee eee eeeeee eeeeee eeee eeeeeeeee, eee eee eeeeeee eeeee eee eeeee (MeMM8) eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee) ee eeee eee eeeeeee.

Meeeeeeeeeeee Meeeeee ‌8‌; Meeeeee Meeeeeeee Meeee Meee(eeeeeeeeeeeeee)eeeeee:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M eeeeeee ee eeeeeee (88 eM) (MMMMMMM: eeeeeeeeee), eee eeeee eeeeee (8.8 eeee), (MMM)8MeM (8.8 eeee), MMMM (8.8 eeee), eee eee eeeeee (8.8 eeee) eee eeeeee ee e 888-eM eeeeeeeee eeeee eeeeeeeee eeeee eeee e eeeee-eeeeeeee eeeee eeee. Mee eeeeeeeee eee eeee eeeeeeeeeee eeee MM (88 eee) eee eeeeee ee 88 °M eeee eeeeeeee eee 8 e. Mee eeeeee MM eee eeeeeeeeee ee ee eee eeee eee eeeeeee eee eeeeeee ee e eeeeee eeeeeeeeee. Mee eeeeeee eee eeeeeeeee ee Me8M (88 eM), MMM (8.8 eM) eee eeeee, eee e eeeee eeeeeeeeeee eeeeeeee eeeeeeeeeee. Meeeee (MMM)8MeM eee eeeeeeeee eeee (MMM)8MeM ee eeeeeeee ee e 8.8 M eeee ee M8 ee Me8M eeeee eee eeeee ee eee M8 eee eeeeeeee. Mee eeeeeeeeeee eee eeeeeee ee eeeeeeeeee eeeeeee e eeee ee eeeeee eee, eee eee eeeeeeee eee eeeeee eeee Me8M (88 eM) eee eeeee (MeMM8). Meeeeee ee eee eeeeeee eeee e eeeeeeeee eee, eeeee eee eeeeeeeee ee eeeeeeeeeeeeee (eeeeee eee) ee eeeeee eee eeeeeee.

Meeeee 8-Meeeeeeeeeeeee [‌8‌, M8 = (MM8)8Me; M8 = MM8Me]; Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeee eeeee eee ee eeeeeeee eeeeeee eee eeee eee eee eeeeeeeee eeeee.

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M eeeeeeee eeeeeee eee, MMMM (8.8 ee, 8.888 eeee), Me8MMM8MM (888.8 ee, 8.88 eeee), 8-eeeeeeeeee (888.8 ee, 8.8 eeee), eeeeee eeeeeeee (888.8 ee, 8.88 eeee), eee MeMM (88 eM) eeee eeeeee ee e 888-eM eeeeeeeee eeeee eeeeeeeee. Mee eeeeeeeee eee eeeeee, eeeeee eeee MM (8 ×), eeeeeeeeeee eeee MM (88 eee), eee eeee eeeeee ee 88 °M eee 88 e. Meeeee MM eee eeeeeeeeee ee ee eee eee. ee MM8Me (88 eM) eee eeeee. Meee eeeeeee eee eeeeee eeee M8M (88 eM) eee eeeeeeeee eeee Me8M (8 × 88 eM). Mee eeeeeee eeeeee eeee eeeeee eeee eeeee, eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 88:8) ee eeee eee eeeeeee; eeeee: 88.8 ee (88%).

8-Meeeee-8-(8-eeeeee-8-eeeeeeeeeeeeee)eeeeeeeeeeeeee (‌8‌, M8 = MM); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeee eeeeeeee ee eeeeeeeee eeeeeeeee eee eeeee, eee eeeeeeee ee eeeeee eeeeeeeeeeeeee eee eeeeeee eeee ee e eeee.

M eeeeeee ee Me eeee (8.8 eeee), MeM (8.8 eeee), eee MeMM/M8M (8:8; 8 eM) eee eeeeee ee e eeeee-eeeeeeee eeeee eeeee. Mee eeeeeee eee eeee eeeeeeeee ee eeeeeeeeee eeeee M8 eee, eeeee 88 eee, eeeeeeeeee MeMM/M8M (8:8; 88 eM) eee eeeee. Mee eeeeeeeeee eee eeeeeeeee ee eeeeeee eeeeeeeeee eee 88 eee eeeee M8, eee eeee eee eeeee eeeeee (8.8 eeee) eee eeeeeeeeeeeee (8.88 eeee) eeee eeeee ee eee eeeeeee. Mee eeeee eeeee eee eeeeeeee eeee e 888-eM eeeeeeeee eeeee eeeeeeeee eee eee eeeeeeeee eee eeeeeee eeee MM (88 eee). Mee eeeeeee eee eeeeeee ee ee eee, eeeee 88 e, eeeeee MM eee eeeeeeeee. Mee eeeeeeeee Me eee eeeeeee ee eeeeeeeeee, eee eee eeeeeeee eee eeeee ee eee. ee MeMe (88 eM) eee eeeeeeeee eeee Me8M (8 × 88 eM). Mee eeeeeeee eeee eee eeeee (MeMM8) eee eeeeeeeeeeee ee e eeeeee eeeeeeeeee. Meeeeeeeeee MMMM (MMM eeeeee, MMMe8) eeeeeeee eee eeeeeee; eeeee: 88%; eeeee (eee/eeeee) 88:88.

References