Science of Synthesis

Suginome, M.; Ito, Y., Science of Synthesis, (2004) 19, 461.

Phosphoryl chloride is now one of the most popular dehydrating reagents in isocyanide synthesis. Typically, a slight excess (ca. 1.1 equiv) of phosphoryl chloride is used with a base such as triethylamine, diisopropylethylamine, diisopropylamine, pyridine, or potassium tert-butoxide.[‌41‌,‌54‌] ‌Scheme 24‌ illustrates representative isocyanides ‌41‌ synthesized by using the phosphoryl chloride/diisopropylamine system.[‌55‌]

‌Meeeee 88‌ Meeeeeeeeee Meeeeeeeeee ee eee Meeeeeeeee Meeeeeee/Meeeeeeeeeeeeeee Meeeee[‌88‌–‌88‌]

‌Meeeeeeeeee 88‌

M8	Meeee (%)	Mee
MM8MM8Me	88	[‌88‌]
MM8MM8Me	88	[‌88‌]
MM(eMe)MM8Me	88	[‌88‌]
8-Mee	88	[‌88‌]
	88–88	[‌88‌]
Me	88–88	[‌88‌]
8,8,8-eMe8M8M8	88	[‌88‌]
8-M8MM8M8	88	[‌88‌]
8-MMMMMMM8M8	88	[‌88‌]
	88	[‌88‌]
MM8Me	88	[‌88‌]
	88–88	[‌88‌]
	88	[‌88‌]

Meee eeeeee eeeee eeeeeeeee eeee-eeeeeeee ee e eeee ee eeeeeeee eee eee eeeeeeeee ee eeee eeeeeeeeeee; eee eeeeeeeee eeeeee eeee eeeeeeee: eeeeee (88%), 8-eeeee (88%), 8,8-eeeeeeeeeeeeee (88%), eeeeeee (88%), 8-eeeeeeeeeeee (88%), 8-eeeeeeeeeeee (88%), 8-eeeeee-8-eeeeeeeeeeee (88%), 8-eeeeeeeeeeeee (88%), 8-(eeeeeeeeeeee)eeeeee (88%), 8-eeeeeeeeeee (88%), eee 8-eeeeeeee eeeeeeeeee (88%). Meeeee eeeeee eeee eeeeeeee ee eee eeeeeeee eeeeee (eee Meeeeee ‌88.8.8.8.8.8‌), eee eeeeeeee ee eeeeee eeeee. Meeeeeeee eeeeeeeeeee eee eeeeeeeee eeee eeeeeeee ee eeeee eeeee eeeee eeee ee eeeeeeee eeee eeeeeeeeee eeeeeeee.

Meeeeeee eeeeeeeeee eeeeeeee eeeee eeeeeee eeeee eeeeeee eeeee eeee eeee eeeeeee ee eeeeeee eeeeeee eeeeeeeee eee eee eeeeeeeee ee eeeeeee-eeeee eeeeeeeeeee. Mee eeeeeee, ee eee eeeeeeeee ee eeeeeee-eeeee eeeeeeeeee ‌88‌ (MMMMeee), eeeeeeee eeeeeee e eeeeeeeee-eeeeeeeee eeee-eeeeeee eeeeeeeeee eeeeeeeeeeeeee, eeeeeeee ee eee eeee-eeeeeee eeeeeeeeee eeeeeeeeeeeeee ee eee eeeeeeeeee ‌88‌ eeeeeeee ee eeeeeeee eeeee eeee (‌Meeeee 88‌),[‌88‌] eeeeeee e eeeeeeeeee ‌88‌ eeeeeee e eeeeeeeee eeeee eee ee eeeeeeeeeeee eeeeeeeeeee ee eeee e eeeeeeeeeeeee ‌88‌ eeee eeeeeeeee eeeeeeeeeee eeee eeeeeeeeee eeeeeeee/eeeeeeeeeeeeeeee ee eeee eee eeeeeee eeeeeee-eeeeeeeee eeeeeeeeee ‌88‌, eeeeee ee eee eeeee-eeeee eeeeeeeeeeeee eeeeeeeee ee eeeeeeee (eee Meeeeee ‌88.8.8.8.8‌).

‌Meeeee 88‌ Meeeeeeee ee MMMMeee-Meeeeeeee Meeeeeeeeee Meeeeeeeee eeeeeee Meee-Meeeeee Meeeeeeeee Meeeeeeeeeeeee ee Meeeeeeeee-Meeeeeee Meeeeeeee[‌88‌]

Meeeeeeeee eeeeeeee eee eeee ee eeee ee eeeeeee eeeeeee-eeeeeeeeeee eeeeeeeeeeeeeeee ‌88‌ eeee eee eeeeeeeeeeeee eeeeeeeeeee ‌88‌ (‌Meeeee 88‌).[‌88‌] (±)-Meeeeeeeeee M (‌88‌) eee eeee eeeeeeeeeee eeee eeeeeeeee ‌88‌ eeeee eeeeeeeeee eeeeeeee eee eeeeeeee ee eeee (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeeeeee ee 8-Meeeeeeeeeeee Meeeeeeeee[‌88‌]

‌Meeeee 88‌ Mee Meeee Meee ee eee Meeee Meeeeeeee ee Meeeeeeeeee M[‌88‌]

α-Meeeeeee eeeee eeeeee ‌88‌ eee ee eeeeeee eeeeeeeeeee eeee eeeeeeeeeeee eeeeeeeee α-eeeee eeee eeeeee, e.e. Meee eeeee ‌88‌ (‌Meeeee 88‌).[‌88‌] Meeeeeeee eeeeeeee ee Meee eeeee ‌88‌ eeee eeeeeeeeeeeeeeeeeeeeeee eeeee eeeee ‌88‌ (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeeeeee ee α-Meeeeeee Meeeee Meeeeeeee ee Meee Meeee[‌88‌]

‌Meeeee 88‌ Meeeeeeee ee ee Meee Meeeeeeeee Meeeeeeee ee Meee Meeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeeeeeee ‌88‌ eeee Meeeeeeeee; Meeeeee Meeeeeeee:[‌88‌]

MMMe8 (8.88 eee) eee eeeee eeeeeeee eeee eeeeeeee ee e eeee ee e eeeeeeeeee ee eee eeeeeeeee (8.8 eee) eee eMe8MM (8.88 eeee) ee MM8Me8 (888 eM) ee 8°M. Meeeeeee eee eeeeeeeee eee 8 e ee 8°M eee, ee eee eeee ee eeeeeeeee eeeeeee eeeeeeeeee, eee 8 e ee ee. M eeee ee Me8MM8 (88 e) ee M8M (888 eM) eee eeeee ee e eeeeeeeeeeee eeee eeee ee eeeeeeee e eeeeeeeeeee ee 88–88°M. Meeee eeeeeeee eee 8 e ee ee, eeee M8M (888 eM) eee MM8Me8 (88 eM) eeee eeeee eee eee eeeeeee eeeee eee eeeeee eeee M8M (8 × 88 eM), eeeee (Me8MM8), eee eeeeeeeeee. Mee eeeeeee eee eeeeee eeeeeeeee ee eeeee ee eeeeeeeeeeeeee eeee ee eeeeeeeeeee eeeeeee.

8-(eeee-Meeeeeeeeeeeeeeeeee)eeeeee Meeeeeeeee (‌88‌, M8 = 8-MMMMMMM8M8); Meeeeee Meeeeeeee:[‌88‌]

e-MeMeMe8Me (88.8e, 888 eeee) eee eeeee ee e eeeeeeeeee ee (8-eeeeeeeeeeeee)eeeeeeeee (88.8 e, 888 eeee) eee eMe8MM (88 eM, 8.88 eee) ee MM8Me8 (888 eM) ee ee, eee eee eeeeeee eee eeeeeeee eee 8 e. Meeee eeeeeee ee 8°M, MMMe8 (8.88 eee) eee eeeee eeeeeeee eeee eeeeeeee. Meeee eeeeeeee eee 8 e ee 8°M, e eeee ee Me8MM8 (88 e) ee M8M (888 eM) eee eeeee eee eee eeeeeee eeeee eee eeeeee eeee M8M (8 × 88 eM), eeeee (Me8MM8), eee eeeeeeeeee. Meeee eeeeeeeeeee ee eee eeeeeee, eee eeeee eeeeeee eee eeeeeeeee ee eeeee ee eeee e eeeeeeeee eeeeee; eeeee: 88.8 e (88%); ee 88–88°M (8.8 Meee).

8-Meeee Meeeeeeeee (‌88‌, M8 = 8-Mee); Meeeeee Meeeeeeee:[‌88‌]

Meeeeeeee eeee (Mee; Meee, Meeeeee Meeeeeeee, Meeeeeeeee Meeeee M), Meeeeeeee (8888), e 8888, eeee eeeeeeeeee eeee Meee Meeee&Meee, Mee.

MMMMMMM: Meeeeeee eeeeeeeee ee eeeeeeeee eeeeeee ee eee eeeee e eeeeeee ee eeeeeeeee eeeeeeeeee, eeeee ee eeeeeeeee eeeee eeeeeee eeeeeeeeee.

M (888 e, 8.8 eee), eee eeee eeeee eee eeeeee, eee eeeee eeeeeeeeeee ee eee e-MeMM (8888 eM). Mee eeeeeee eeeeee eeeeeeeee ee eee eeeeeeeee eeeeeee eeee eee eeeeeee. Mee eeeeeeee eeee eee eeeeeeeeee ee eeeeeeeee eee eeeeeeee eeeee ee eeee eee eeeeeee eeeeeeee eeeeee. Me eee eeeeeeee eee eee eeeeeeee, eee eeeeeeee eee eeeeeee, eee, ee eeeeeeeee, eee eeeeeeee eeeeee eee eeeeee ee eeeeeeeee ee e eeee eeee. e-MeMM eeeeeeeee eeeeeeeeeeee, eee eee eeeeeee eeeeee e eeeee eeeeeeeeee eeee eee eee eeeeeeeee eee eeeeeee. 8-Meeeeeeeeeeeee (M8 = 8-Mee; 888 e, 8.8 eee) eee eeeee ee eee eee eeeeeee eeeeeeeeee, eeeee eeeeee e eeeee eeee eeeeee e eee eeeeeee. Mee eeee eee eeeeee ee 88–88°M ee eeeeeeeee ee ee eee eeee eee eeeeeeeeee ee eeee eeeeeeeeeee eeeee MMMe8 (88 e, 8.88 eee) eee eeeee ee ee eeee eeeeeeee eeeeee 88–88 eee. Mee eeeeeee eee eeeeeee ee 88–88°M eee 8 e eee eeeeee eeee ee eee-eeee eeeeeee eeee ee MeMMM8 (88 e ee 8 M ee M8M). Mee eeeeeee eee eeeeeeeee eeee eeeeeeeee eeeee eee eee eeeeeeee eeee eeeeee eeee MeMMM8 (8%), eeeee (MMM, 88 e), eee eeeeeeeee (88–88°M/88 Meee) eeeeeee e Meeeeee eeeeee; eeeee: 88–88 e (88–88%).

Meeeeeeeee Meeeeeeeee (‌88‌, M8 = Me); Meeeeee Meeeeeeee:[‌88‌]

Meeeeeeee eeee (Mee; Meee, Meeeeee Meeeeeeee, Meeeeeeeee Meeeee M), Meeeeeeee (8888), e 888, eeee eeeeeeeeee eeee Meee Meeee&Meee, Mee.

MMMe8 (88 e, 8.88 eeee) eee eeeee eeeeeeee eeee 88–88 eee ee e eeee ee eeeeeeeeeeeeeeeeeee (M8 = Me; 888 e, 8.8 eee) eee eeeeeeee (888 eM, 8.8 eee) ee eeeeeeeee eeeee (888 eM) eeeeee ee 8°M. Mee eeeeeee eee eeeeeee eeeee eeeeee eee 88 eee eeeee eee eee MMMe8 eee eeeee. Mee eeeeeee eee eeee eeeeee ee 8–8°M. Me eee eeeee eeeeee, eee eeeee (888 eM) eee eeeeeeeee eeeee eeee eeeeeeee, eeeee eee eeeeeeeee eeeee eee eee eeeee eeeeeeee eeeeeeeee. Mee eeeeeee eee eeeeeeeee eeee eeeeeeeee eeeee, eee eee eeeeeeee eeee eeeeee eeee M8M, eeeee (MeMM8, 88 e), eee eeeeeeeee (88–88°M/88 Meee) eeeeeee e Meeeeee eeeeee; eeeee 88–88 e (88–88%).

Mee eeeeeeeee eeeeeeeee eeeeeeeeeee eeee eeeeeeeee eeeeeeee: eMeMM (88%), MeMM (88%), e-MeMM (88%), eee MeMM (88%).

Meeeeeeeeee Meeeeeeeee (‌88‌, M8 = MM8Me):[‌88‌]

Meeeeeeee eeee (Meeeeeeeee; Meeeeeeee; eee Meeeee, Meeeeee Meeeeeeee, Meeeeeeeee Meeeee MM), Meeeeeeee (8888), e 888, eeee eeeeeeeeee eeee Meee Meeee&Meee, Mee.

M eeee ee MMMe8 (88 eM, 8.88 eee) ee 8,8-eeeeeeeeeeeeee (88 eM) eee eeeee eeee e eeeeeeee eeeeee ee e eeeeeeeeee ee (eeeeeeeeeee)eeeeeeeee (M8 = MM8Me; 888 e, 888 eeee) eee Me8M (888 eM, 8.88 eee) ee MMM (888 eM) eee Me8M (888 eM) eeeeee ee −8°M ee e eeee eeee eeee eee eeeeeeeeeee eeeeeee −8 eee 8°M. Meeee eeeeeeee eee eeeeeee 88 eee ee 8°M, eee eeeee (8.8 M) eee eeeee ee eee eeeeeee eeee eeeeeeeeee eeeeeeee. Meeee eeeeeeee eee ee eeeeeeeeee 88 eee, eee eeeeeeeeeeee eeee eeeeee eeee eeeeeeeee ee eeeeeeeeee eee eeeeee eeee eeee eeeee (888 eM). Mee eee eeeeeee eee eeeeeeeee ee eeee (88–88°M) eeeeeee (888 eM) (MMMMMMM: eeeeeeeeee), eee eeeeeee eeeee eee eeeeeee eeee e eeeeeeeeee eeeeee, eee eee eeee eeeee eeeeeee eeee eee eeeee (MeMM8). Mee eeee eee eeeeeee eeee eeeeeeeee eeeeee (8 e) ee 88°M eee 8 eee eee eeeeeeee. Meeeeeeee eeeee eee eeeee ee eee eeee ee eeeeee eeeeeeeeeeeeeee ee eee eeeeeee. Mee eeeeeeeeeeee eeee eeeeeeeee ee eeeeeeeeee eee eeeee ee eeeee; eeeee: 88–88 e (88–88%).

8-[(Meeeeeeeeeeeee)eeeeeee]eeeeee Meeeeeeeee (‌88‌, M8 = MMM); Meeeeee Meeeeeeee:[‌88‌]

MMMe8 (8.88 eM, 88.8 eeee) eee eeeee eeeeeeee ee 8°M eeee 88 eee ee e eeeeeee ee {8-[(eeeeeeeeeeeeee)eeeeeee]eeeeee}eeeeeeeee (‌88‌, M8 = MMM; 8.88 e, 88.8 eeee) eee Me8M (8.88 eM, 88 eeee) ee MMM (88 eM). Mee eeeeeee eee eeeeeee ee 8°M eee 8 e eeee eee. ee MeMMM8 (88 eM) ee 8°M eee eeeee. Meeeeeeeee eeee MeMMe eeeeeeee ee eeeeee eeeeeeeeeeeeee (Meeeeeee, eeeeee/Me8M 8:8) eeee e eeee eeeeee eee; eeeee: 8.88 e (88%).

(±)-Meeeeeeeeee M (‌88‌):[‌88‌]

MMMe8 (88 μM) eee eeeee ee e eeeeee (−88°M) eeee ee eee eeeeeeeee ‌88‌ (8.8 ee, 8.88 eeee) ee eeeeeeee (8.8 eM) eeeee eeeee eee eee eeeeeee eee eeeeeee ee −88°M eee 88 eee. Me MeMMM8 eeee eee eeeee eee eee eeeeeee eeeeeeee eee eeeeeeeee eeee 88% MeMM ee MM8Me8. Meeeeeeeeee MMM (eeeeee/MeMMe 8:8) eeee eee eeeee eeeeeeee; eeeee: 8.8 ee (88%).

Meee Meeee Meeeeeeee α-Meeeeeee Meeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeeeeee eeeee eeee eeeee eeeee eee eeeeeeeeeee eee eeeee. Mee eee eeeeeeeeeee eeeee eee eeeeeeeee ee MM8Me8. Meeeeeee (8 eeeee), MMM8M (8 eeeee), eee eeee eeeeeeeeeeeeeeeeeeeeeee (8 eeeee) eeee eeeee eeeee eee eeeeeee. Mee eeeeeeeeee eee eeeeeee eee 8 e ee 8°M eee eeee ee ee eee 8 e. Mee eeeeeeeeee ee eee eeeeeeee eee eeeeeee ee eee eeeeeeeee eeee. Mee eeeee eee eeeeee eee eeeee eee eee eeee eeee. Mee eeeeeeeeee eeeee eeee eeeee ‌88‌ eee eeeeeeeee ee eee MM8Me8 eee eMe8MMe (88 eeeee) eee eeeee eeee eee eeeeeee eeeee eeeee. MMMe8 (8 eeeee) eee eeee eeeeee eeeee eee eee eeeeeeeeee eee eeeeeee eee 8 e ee 8°M eee 8 e ee ee. Mee eeeeeeeee eeeee ‌88‌ eee eeeeee eeee MM8Me8 eee Me8M eee eeeee ee eeeee ee e eeeeeeee eeeeee. Mee eeeeeeeeeeeee ee eeeeee MM (∼8888 ee−8) eee eee eeeeeeeee ee MM (∼8888 ee−8) eeeeeeeeee ee eee MM eeeeeeee eeeeeeeee eee eeeeeeeee ee eee eeeeeeeeee.

Meee Meeeeeeeee Meeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

Meee eeeee ‌88‌ eee eeeeeeeeeee eee eeeeeeeee ee MM8Me8. Meeee eee eeeeeee, eeeeeeee (8 eeeee) eee MMM8M (8 eeeee) eeee eeeee, eeeeeeee ee eeeeeeeeeeeeeeeeeeeeeee (8 eeeee). Mee eeeeeeeeee eee eeeeeee eee 8 e ee 8°M eee eeee ee ee eeeee eee eeeeeeee eee eeeeeeee, ee eeeeee ee eee Meeeee eeee. Mee eeeee eee eeeeee eeeeeeeeeeee eeee MMM, MeMM, eee MM8Me8. Mee eeeeeeeeee Meee eeeee eee eeeeeeeee ee eeeee MM8Me8. Meeee eee eeeeeee eee eeeee eeeeeeeeee, eMe8MMe (88 eeeee) eee eeeee eeeeeee e eeeeeee. MMMe8 (8 eeeee) eee eeee eeeee eeeeee. Mee eeeeeeeeee eee eeeeeee eee 8 e ee 8°M eee 8 e ee ee. Mee eeeee eee eeee eeeeee eeee MM8Me8 eee Me8M eee eeeee eeeee eeeeee ee e eeeeeeee eeeeee ee eeee ‌88‌.

References