Science of Synthesis

Murahashi, S.-I., Science of Synthesis, (2004) 19, 356.

Addition of carbon nucleophiles to the C≡N bonds of nitriles is one of the most attractive transformations of nitriles. The reported methods are limited to strong-base promoted intramolecular cyclization reactions of dinitriles (Thorpe–Ziegler reaction). The reaction of nitriles with strong bases generates nitrile anions that attack the neutral nitrile to generate an intermediate imine, which undergoes isomerization and protonation to give the enaminonitrile.[‌80‌–‌82‌] The Thorpe–Ziegler dinitrile cyclization provides a powerful method of assembling 5- to 33-membered rings.[‌11‌,‌80‌] Dinitrile cyclizations of five- and six-membered rings are particularly facile with analogous seven- or eight-membered rings being similarly efficient. Traditionally, dinitriles have been cyclized using sodium hydride, alkoxide, and amide bases,[‌83‌] although in some favorable instances very weak bases are effective for the cyclization.[‌84‌]

Meeeeeeeeee, eeee e eeeeee-eeee-eeeeeeee eeeeeeee eee ee eeeeeee eee eeee eeeeeeeeeee eeeee eeeeeee eeeeeeee(eeeeeee)eeee(eeeeeeeeeeeeeeeeee)eeeeeee(M) eee eeeeeeeeeeeeeee(eeeeeeeeeeeeeeeeeeeee)eeeeeee(M) eeeeeeeee.[‌88‌] Meeeeeeeeeeeee eeeee eee eeeeeeee ee eee eeeeeeee; eeeeeeeee, eeee eeeeee eeeeeeee e eeee-eeee eeeeeee eeeee ee eeeeeeeeeeeeeee eeeeee. Me eee eeeeeeee ee eeeeeeee(eeeeeee)eeee(eeeeeeeeeeeeeeeeee)eeeeeee(M) eeeeeeee, eee eeeeeeeeeeee ee eeeee eeeeeeeeeeee eeeee eee M-eeeeeeeeeeee eeeeeeeeeee (>88% eeeee).[‌88‌]

Me eeeeeeeee eeeeeee ee eeee eeeeeeee ee eee eeeeeeeeeeeeee eeeeeeee ee eeeeeeeee eeeeeeee ee eee M≡M eeeee ee eeeeeeee ee eee eeeeeeee ee eeeeeeee eeeeee; eeee ee eeeeeee ee eee eeeeee eeeeeeeeeeee eeeeeee ee eeeeeeee eeeeee eeeeee. Mee eeeeeeee(eeeeeee)eeee(eeeeeeeeeeeeeeeeee)eeeeeee(M)-eeeeeeeee eeeeeeee ee eeeee eeeeeeeeeeee ee 8-eeeeeeeeeeeeeeeeee eeeee eeeee (M)-8-(8-eeeeeeeeeeee)-8-eeeee-8-eeeeeeeee-8-eeeeee (88%) eeeeeeeeeeeeeeee, eeeee eee eeee eeeeeeee eeeeeeee ee e eeeeeeeeeeee eeee eeee ee eeeeeeee eeeeeee eeeee eeeee 8-eeeee-8-(8-eeeeeeeeeee)eee-8-eeeeee (M/M 88:88) (‌Meeeee 88‌). Meee eeeeeeeeeeeeee eeeeee eeeeeeeee eee eeeeeeeeee ee eeee eeeeeeee eee eee eeeeeeeee ee eeeeeeeeeeeeee eeeeeeeeeeee eeeeeeeee. Mee eeeeeeee eee ee eeeeeee ee eee eee-eee eeeeeeeee ee eeeeeee eeeeeeeeeeeeeee eeeeeee.

Me eeeeeeee eeeeee eeeeeeeeeeeeee, eee eeee eeeeee eeeeeee eeeeeee eeeeeeee, eeeeeeeeeeeeeee(eeeeeeeeeeeeeeeeeeeee)eeeeeee(M) ee eeeeeeee. Mee eeeeeeeeeeeeeee(eeeeeeeeeeeeeeeeeeeee)eeeeeee(M)-eeeeeeeee eeeeeeeeeee ee eeeeeee-8,8-eeeeeeeee eeeee eee eeeeeeeeeeeeee eeeee eeeeeee eeeeeeeeee ee 88% eeeee.[‌88‌] Meeeeeeeeeeeeee(eeeeeeeeeeeeeeeeeeeee)eeeeeee(M) eeee eeeeeeeee eee eeeeeeeeeee ee 8-(8-eeeeeeeeee)eeeeeeeeeeee ee eeee 8-eeeee-8M-eeeeee-8-eeeeeeeeeeee (‌88‌) ee 88% eeeee. Mee eee eeee ee eeeee eeeeeeeee ee eee eeeeeeeeeeee eeeeeeeeee ee eeee eee α-M—M eeeee ee eee eeeeeee ee eeeeeeeeeeeeeee, eee eee M≡M eeeee ee eee eeeeeeee ee eeeeeeeeeeeee.[‌88‌] Meeeeeee ee eee Meeeee–Meeeeee eeeeeeee ee eeeeeeee eee eeeee ee ‌Meeee 8‌.[‌88‌–‌88‌]

‌Meeeee 88‌ Meeeeeeeeeeeee Meeeee–Meeeeee Meeeeeee[‌88‌]

‌Meeee 8‌ Meeeee–Meeeeee Meeeeeeee[‌88‌–‌88‌]

Meeeeeee	Meeeeee ee Meeeeeee	Meeeeee	Meeee (%)	Mee
MM(MM8)8MM	MeMMe, MeMM, eeeeee		88	[‌88‌]
MM(MM8)eMM, e = 8, 8	MeMM(MMe8)8		88–88	[‌88‌]
MMMM8MM8Me	[MeM(MM)(MMe8)8] (eee.)		>88	[‌88‌]
MMMM8MM8e-Me +MeMMM8MM	[MeM(MM)(MMe8)8] (eee.)		88	[‌88‌]
MMMM8MM8Me +MM(MM8)8MM8Me	[MeM(MM)(MMe8)8] (eee.)		88	[‌88‌]
	[MeM8(M-eMe8)8] (eee.)		88	[‌88‌]
MeMM	[MeM8(M-eMe8)8] (eee.)		88	[‌88‌]

Meeeeeeeeeee Meeeeeeee

8-Meeee-8M-eeeeee-8-eeeeeeeeeeee (‌88‌); Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee 8-(8-eeeeeeeeee)eeeeeeeeeeee (8.888 e, 8.8 eeee) eee MeM8(M-eMe8)8 (8 eee%) ee eee eeeeeee (8.8 eM) eee eeeeeee ee 888°M eee 88 e eeeee eeeee ee e eeeeee Meeee eeee. Meeee eeeeeee ee eee eeeeeee, eee eeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee); eeeee: 8.888 e (88%); ee 888.8–888°M.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) M 8-8, 8888.
• 8.Meeeee-Meee, (8888) M 8-8, 8888.