Science of Synthesis

Witulski, B.; Alayrac, C., Science of Synthesis, (2006) 24, 1007.

General Introduction

Stable members of this product subclass are represented by the N,N-disubstituted alk-1-yn-1-amines ‌1‌; they are extremely electron-rich compounds since the amino function is conjugated directly with the triple bond (‌Scheme 1‌). The first example was obtained, by chance, through a reaction between 3-bromoprop-1-yne and phenothiazine, which takes place by a hitherto unknown propargylamine to ynamine rearrangement.[‌1‌] Two years later, the synthesis of N,N-diethylacetylenamine was achieved, but the yield was only 2%.[‌2‌] The first reliable method for the preparation of these compounds was reported in 1963; it is based upon the treatment of 1-chloro-1-fluoroethene with lithium dialkylamides.[‌3‌] Since then, new methods have been developed that rely either on substitution, elimination, isomerization, or on fragmentation reactions.[‌4‌–‌10‌] N,N-Disubstituted acetylenamines are used in a broad range of addition and cycloaddition reactions and, to a lesser degree, as building blocks in organic synthesis.[‌4‌–‌11‌] They can also serve as dehydrating agents in peptide synthesis, and in esterification reactions.[‌5‌] N,N-Disubstituted 2-acylalk-1-yn-1-amines ‌2‌ (‌Scheme 1‌), so-called push–pull-substituted ynamines, are also useful activating agents in peptide synthesis.[‌12‌–‌14‌]

Mee eee-8-ee-8-eeeeee ‌8‌ eee ‌8‌ eeeeee eeeeee e eeeeeeeee ee eeeeeee eeeee eeeeeeee eeeeeee eeeeeeeeeee ee eee eeeeeeeeeeeeeeeee eeee eeeeee eeeeeeeeeee ‌8‌ eee eeeeeeee ‌8‌, eeeeeeeeeeee, eee eeeeeee ee eeee eeee eeeeee ee eeeeeeee eeeee eeeeeeee eeeeeeeeee eeeeeeeeee (‌Meeeee 8‌).[‌8‌] Meeeeee, eeeeeee eee eeeeeeeee eee-8-ee-8-eeeeee eee ee eeeeeeee eee eeeeeeeeeeeee ee ee eeeee eeeeee (−888°M) ee ee “eeeeee eeeeeeeee” ee eee eee eeeee.[‌8‌]

‌Meeeee 8‌ Mee-8-ee-8-eeeeee eee Meeee Meeeeeeeeeeee Meeeeeee[‌8‌–‌88‌]

Mee eeeeeee, eee eeeeeeeee eee eeeeeeeeeeeeee ee eeeeeeeee eee-8-ee-8-eeeeee ‌8‌ eee eeeeeeee ee 8888 ee eeeee-eeeeee eeeeeeeee ee eeeeeeeeeee eeeeeeee-8(8M)-eeee.[‌88‌] Mee eeeeeeeee ee eee eeeeee eeeeeeee, eeeeeeeeeeeee (‌8‌, M8 = M), eee eeeee eeeeeeeee ee 8888, eeee ee eee eeeeeeeee ee eee eeeee-eeeeee eeeeeeeee ee “eeeeeeeeeeeeeeeeeeeeeeee”.[‌88‌] Mee eeee eeee, eeeeeeeeeeeee eee eeeeeeee eee eeeeeeeeeeeee ee eee eee eeeee ee eeeeeeeeeeeeee/eeeeeeeeeeee eeee eeeeeeeeeeee.[‌88‌,‌88‌] Mee eeeee eeeee, eeeeeeeeeeeee eee 8-eeeeeeeeeeeeee-8-eeeee (‌8‌, M8 = Me) eeee eeeeeeee ee eeeee-eeeeee eeeeeeeee eeeeeeeeeee eee eeeeeeeeee ee eee-eeeeeeeeeee MM eeeeeeeeeeee.[‌88‌] Meeeeeeeeeeee ee eeeeeeeeee ee ee ee eeeeeeeee eeeeeeee ee eeeeeeeeeeeee eeeeeeee, eeeeeee ee eeeeeee eeeeeeee ee eeeeeeeeeee eee eeeeeeeee ee eee eeeeeeeeeeee eeeeeeeee ee eeeeeeeeeeee.[‌88‌]

Meeeeeeeeee eeeeeeeee eeeeeee ee eeee eeeeeeee eee ee eeeee ee Meeeee–Meee, Mee. 8/8e, ee 888–888, eee Mee. M 88, ee 8888–8888. Mee eeeeeeeee, eeeeeeeeee eee eeeeeeeee ee eee-8-ee-8-eeeeee eeee eeee eeeeeeee,[‌8‌–‌88‌] eee eeeeee eeeeeeeeeeee eeeeeeeeee eee ee ee eeeee ee e eeeeeeeee.[‌88‌]

Me eeeeeee, eee-8-ee-8-eeeeee ‌8‌ eee eeeeeeeee eeeeee, eeeeeeeeee ee M8 ee eeee eeeeeeeeeee;[‌8‌–‌88‌] eee eeeeeee, M,M-eeeeeee-8-eeeeeeeeeeeeee-8-eeeee eeeeeeeeee eeeeeee ee ee 888°M. Mee eeeeeee eeeeeeeee ee eee eee-8-ee-8-eeeeee ‌8‌ ee eee eeeeeee ee eee eeeeeeee ee e eeeeeeeeeeeee eeeee ee M8; eeeeeee, eeeee eeeeeeeee eeeeeeeee eee eeeeee eeeeeeeee eeeeee eeeeeeeeee, eeeeee eeee eeeee eeeeeeeee ee eeeeee. Mee eeeeeeeeee ee eee eee-8-ee-8-eeeeee ‌8‌ eeeeeee eeee eee eeeeeeeeeeeeee ee eee eeeeeeee eeee eeee ee eee M-eeee eeee eee eeeeeeee eeeeee eeee, eeeeeeeee ee ee eeeeeeee-eeee eee eeeee β-eeeeee (M8) eeeeee. M-Meeeeeee eeeeeeeeeeeeee ‌8‌ eee eeee eeeeee eeee eeeee M-eeeee eeeeeeeee eee ee eeeeeee eeeeeeeeeee eeeeeee. Mee eeeee eeeeee eeeeeeeee eee eee M,M-eeeeeeeeeeee eeeeeeeeeee eeeeee e eeeeeeee eeeeee eeee; eeee eeeeeeeee eeeeeee eeeeeee eeeeeeeeee ee eeeeeeeeeeeeee. Meeee eee eeeee eeeeeeee, M-eeeeeeeeeeeeeeeeeee ee eee eeeeeee ee eeeeee.[‌88‌] Meeeeeeee eeeeee eeeeeeeeee ee eee eeeeeeee ee eeeeeeeeeeeee ee eeeeeeeeee eeee M8 eeeee ee eeeeeeee-eeeeeeee eeeee (ee ee eee ee-eeeeee eeee–eeee-eeeeeeeeeee eee-8-ee-8-eeeeee ‌8‌ eee 8-eeeeeeeeeeeeeeeeeeeeeee-8-eeeeee ‌8‌) (‌Meeeee 8‌).[‌8‌–‌88‌] Me eeeeeeee, eee-8-ee-8-eeeeee eeeeeee ee eeeeeeee-eeeeeeee eeeee ee eee eeeeeeee eeee eee eeeeeeeeeeeee eeee eeeeee eee eeeeee ee eeeeeeeee eeeeeeee eeeeee ee eeeeeee eeeeeeeee (eee Meeeeee ‌88.8.8.8‌). M eeeeeee eeeeeeee ee eeeeeeeee, eee ee eee eeeeeee ee eeeeeeeeee, ee eeeeeeee eeee eee eeeee eeeee ee eeeeeeeeeee ee eee eeeeee ee, eeee eeeeee, ee eee eeeeeeeeeeeeeee eeeeee.[‌8‌–‌88‌]

Mee-8-ee-8-eeeeee ‌8‌ eee eeeeeeeeeeee eeeeeeee eeeeee e eeeee eeeee ee eeeeeeeeeeeee.[‌8‌–‌88‌] Me eeeeeeeee eeee eeeee eeeeeeeee eeeeeeeeee, eeeeeeeeeeeee eeeeee eeeeee ee eee β-eeeeee eeee (M8), eeeeeee eeeeeeeeeeee eeeeee eee eeee eeeee ee eee α-eeeeee eeee (M8) ee eeeeeeeeeeee ee eeeee ee eee eeeeeeeeeeee eeee (‌Meeeee 8‌). Meee-eeeeeeeee eeeeeeeee ee eeeee, eeeeeeee eeeeeee, ee eeeeeee eeeeee eeee ee eeeeee ‌8‌ (M = M), eeeeeeeeee ‌8‌ (M = M), ee eeeeeeee ‌8‌ (M = MM8), eeeeeeeeeeee (‌Meeeee 8‌).[‌88‌–‌88‌] Meeeeeee eeeeeee eeee eee “eeeeee” eeeeeeee eeee eeee ee eeeeeeee, eeeeeee, eeeeeeeee eeeeee, ee eeeeee eee eeeeeeeeeeeeeeee ee eee-8-ee-8-eeeeee ‌8‌ ee eeee eee eeeeeeeeeeeee eeeeeeee ‌8‌ (‌Meeeee 8‌).[‌8‌,‌8‌] Mee-8-ee-8-eeeeee eee ee eeeeeeee eeee eeeeeee eeee eee ee eeeee MM-eeeee ee eeee eeeeee.[‌8‌,‌8‌] Meee eeee eeeeeee eeeeeeeee eeee eeeee[‌88‌] ee eeee eeeeeeeeeeeee,[‌88‌] ee eee eeeeeeee ee eeeeeeeee(MM) eeeeeeeee, ee eeeeee eee eeeeee ‌88‌ (M = M); eeeeeee eeeeeeeee eeee eeeeeeeee eeeeee eeeee ee eee eeeeeeeeee ‌88‌ (M = M) (‌Meeeee 8‌).[‌8‌,‌88‌]

‌Meeeee 8‌ Meeeeeeeee ee Mee-8-ee-8-eeeeee[‌8‌–‌88‌]

Meee- eee eeeeeeeeeeeee eeeeeeeeeeeeee eee eeeeeeeeeeeee ee eeeeee MM eeeeeeeeeee ee eee eeeeee 8888–8888 eee ee 8888 ee−8, eeeeeeeeeeee, eee ee eeeeeeeeee eeeeeeeeee eeee eee eeeeeeeeeeeeeee eeeeeeeeeee M≡M eeee. Me eee 8M MMM eeeeeee ee eeeeeeee eee-8-ee-8-eeeeee, e eeeeeee ee δ 8.8 ee eeeeeeee eeee eeee eeeee eeeeeeeeeeee eee eeeee, eee ee δ 8.8 eeee eee ee eeee ee ee eeee eeeee.

References

Meeeeee Meeeeeeeeee

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