Science of Synthesis

Heaney, H.; Christie, S., Science of Synthesis, (2004) 3, 625.

One of the most comprehensively studied areas of copper chemistry is 1,4-addition to α,β-unsaturated systems. The fact that this area of chemistry was reviewed 30 years ago gives an indication of the volume of work that has been carried out.[‌131‌,‌201‌] In this respect, dialkylcuprates are among the most widely used reagents since they are reactive, relatively easy to prepare, and, perhaps most importantly, give reproducible results. As with other copper reagents, the source of the copper and the quality of all reagents is of critical importance, and one should always screen a number of different copper reagents in any new reaction. However, in the main, Gilman cuprates react well in conjugate addition reactions and have provided a wealth of mechanistic information over the years. One study that deserves mention is the effect that coordinating solvents have on conjugate addition reactions.[‌1644‌] The necessity of having an ethereal solvent is highlighted in this paper. If a Michael reaction was carried out in toluene, the product of 1,2-addition was isolated. When diethyl ether was used, at least 2 equivalents were required but a significant jump to almost exclusive 1,4-addition was noted. This suggests that theoretical calculations on the stabilization of a copper(III) intermediate during the conjugate process may be correct.

Mee eeeeee eeeeee eeeeeeeeee, eeeeeeeee eeeeeee eeeeeeeeeeeeeeeee, eee eeeee ee e eeee eeeeee ee eeeeeee eeeee eeeee eeeeeeeeeeeee eee eeeeeee. Me eeeeeee, eee eeeeee eee eeeeeeeee eeeeee eeeee ee ee eee eeeeeeee eeeeee, eee eeeeeee eee eeeee ee eeeeeeeeeeeee eeeeeeee (‌Meeeee 888‌).[‌8888‌,‌8888‌] Meee eee eeee eeeeeeeee ee eee eeeeeeeeee eeeeeeee ee eeeeeeeeeeeeeee ee e eeeeeeee eeeee ee eeeeeee eee MM eeee ee eeeeeee M.[‌8888‌]

‌Meeeee 888‌ Meeeeeeee Meeeeeee Meeeeeeee ee Meeeeeeeeeeeeee[‌8888‌,‌8888‌]

Mee ee e eeeeee eeeeeeeee eee eeee eeee eeeeeee eeeeeeeeeee. Me eee eeeeeeeeeeeeee eeeeeeee ee ‌Meeeee 888‌ (e.e., ‌888‌), eee eeeeee eeeeeee eeeeeee eeeeeee ee eee eeeeeeee eeeeee eee eeeeeeeeeeeeeee ee eee eeeeeeee. Me eeeeeee, eee eeeeeee eeee eeeeee eee eeeeeeeee eeee eee eeeee eeeeeeee eeee, eeeeee ee eeeeeee ee eeeeeee eee eeeeeeeeee ee eee eeeeeeee. Meeeee eeeeeeeeee eee eee eeee eeeeee eee eeeeeeee eeee eee eeeeeee eeeeee ee eeeeeee; eeeeeee, eeeeeee eeeeeeeee eeee eeee eeee eeeeeeee.[‌8888‌–‌8888‌] Meeeeeeee eee eeeeeee eeeeeee eeeeeee eee eee eeeeeeee eeee eeeeee ee eeeeeeeeeeeee.[‌8888‌,‌8888‌] Meeeeeeee ee e eee-eeeeeeeeeee eeeeeeeee eeeeeeee ee eeeeeeeee eeeeeeee eee eee eeeeee eeeeeeeeeeeeeee eeeeeeeeeee ee eeeeeee eeeeeee.[‌8888‌]

‌Meeeee 888‌ Meeeeeeee Meeeeeee Meeeeeeee ee Meeeeeeeeeeeeee ee Meeeee Meeeeee[‌8888‌,‌8888‌–‌8888‌]

Me e eeeeeee eeee, Meeeee eee eeeeeeeee ee eeeeeeeee eeeee ee eee eeeeeeeeeeeeee eee eeeeeeeeeee eeeeeeeee eee eeeeeeeee eeeeeeee ee eeeeeeee ee eeeeeee eeeeee, eeeeeeeeeee ee eeee eeeeee eeeee eee eeeeeeeeeeeeeeeeee.[‌8888‌] Me eeeeeee, eeee eee eeeeeeee ee eeeeeee eee eeeee eeeeeeee eeeeeeee eeeeeeeeee ee ee eeeeeeee eeeeeee ee 8°M, eee eeeeeeeee eeeeeeee eee eeeeee eeeeeeeeeee ee e eeeeeeeeeeeee eeeeee. Meee eeeeeeeeeeeeeeeeeeeee ee eeeeeeeeee eeee eee eeeeee, eeeeee eeeeeeeeeee ee eeeeeeeeeee eeeeeeeeee. Meeeeee eeeeeee eeeeeee eeee eeeeeeee eeee eee eeeee eeee ee eee eeeeeeeee ee eee eeeeeeeeee ee eee eeeeeeee eeeeee. Meeeeee, eeeee eeee eeeeeeeeeee eeeeeeeeeee eeeeeee eeeeeeee, eeee eee eeeeee ee eeeeeeeeeeeeeeeeeeeee eeeee eeee eeee eeeeeeeeee ee eeeeeeeeeeeeeee eeee ee eeeeeee eeeee.[‌8888‌]

Meee ee eeeeeeeee ee eeeeeee ee eee eeeeeeee eeeeeeee, eeeeeeeee eeeeeeee eee ee eeeeeeee eeeeeeeeeeeeee ee eeeeeeeee e eeeeee eeeeee ee eeeeeee eee eeeeeeee. Meeeeee eee eeeeeeeeee eeee eeee eeeee eee eeeeeee eeeeeeeeeeee ee eeee eeee, eeeee e eeeeeee-eeeeeee eeeeeeeeeeeeee (‌Meeeee 888‌).[‌8888‌,‌8888‌,‌8888‌]

‌Meeeee 888‌ Meeeeeeeee Meeeeeeee Meeeeeee ee Meeeeeeeeeeeeee Meeee e Meeeee Meeeee[‌8888‌,‌8888‌]

Me eee eeeeeee eeee eeeee eee eeeee eeeeeeeeeeee eeeeeee, eee eeeeeeeeeeee ee e eeeeeeeee eeeeeeee, eee eeeeeee eeeee, eee ee eeeeeee ee eeee eeeeee eeeeeee eeeeeeee. Mee eeee eeeeee ee eeeeeeee eeee e eeeee eeeeeeee ee eeee e eeeee eeee eeeee, e.e. ‌888‌, eeeee ee eeeeeeee ee eee eee eeeee (‌Meeeee 888‌).[‌888‌,‌8888‌,‌8888‌]

‌Meeeee 888‌ Meeeeeeee Meeeeeee–Meeeeee Meeeee ee Meeeeeeeeeeeeee[‌888‌,‌8888‌,‌8888‌]

Meeee eeeeeeee eee eeee ee eeee ee eeeeee eee eeeeeeeee eee eeeeee e eeeeee M—M eeee eeeeeeeee ee eee eeee eee. Meee eeeeee e eeeeee eeeeeeeee eee ee eee eeeeeeeeeeeeee eeeeeeeeeeeeee eeeeeee ee e eeeeeeeeeeeeeee eeeeee. Mee eeeeeee, eeeeeeee eeeee eeeeeee,[‌8888‌] eeeeeee eeeee,[‌8888‌] eeeeeeeee,[‌8888‌] eee eeee eeeeeeeee[‌8888‌] eee eee ee eeeeeee eeee eee eeeeeeeeeeee eeeeeee eeeee (‌Meeeee 888‌).

‌Meeeee 888‌ Meeeeeeee Meeeeeee–Meeeeee Meeeee ee Meeeeeeeeeeeeee[‌8888‌–‌8888‌]

Meee eeeeeee eeeeeeeeee eee ee eeeeeeeeeeee eeee eee eeeeeee, eee eeeeeee eeeeeeee eeeeeeeeee eeeeee eeee eeee ee ee eeee. Mee eeee eeeeee eeeeeeee eee eeeee eeeeeeee eeeeee eee eeeeeeeee ee eeeeee ee eeeeeeeeee. Meee eeeee ee ee eeee eee eeeeeee eee eeeeee eeeeeee eeee eeeeeeeeee eeee, eee eeeee eee eeeeeeeeeeeee eeeeeeeee eeee eeeeee eee eeeeeeee (‌Meeeee 888‌).[‌8888‌,‌8888‌]

‌Meeeee 888‌ Mee ee Meeeeeeeee Meeeee ee e Meeeeeeeeeeeee[‌8888‌,‌8888‌]

Meeeeeeeeeee Meeeeeeee

eeee-Meeee 8-Meeee-8-[(eeeeeeeee)eeeeeee]-8-eeeeeeeeeeeeeeeee (‌888‌); Meeeeee Meeeeeeee:[‌8888‌]

M 8.8 M eeee ee MeMe ee eeeeeee (888 μM, 8.8 eeee) eee eeeee ee e eeeeeeeeee ee MeM (888 ee, 8.88 eeee) ee eee Me8M (8.8 eM) eeeeeeee ee 8°M eee eeeeeee eee 8 eee. Meeee eeeeeee ee −88°M, e eeee ee eeee-eeeee 8-[(eeeeeeeee)eeeeeee]-8-eeeeeee-8-eeeeeeeeeeeeeeeeeee (8.88 eeee) ee eee Me8M (888 μM) eee eeeee, eeeeee ee −88°M, eee eeeeeee eeeeeeeee; eee eeeeeee eee eeeeeeee ee eeee eeeee ‌888‌ ee e eeeeeee ee eeeeeee eeeee eeeeeeeee ee eeeee; eeeee: 88%.

8-Meeee-8-(eeee-eeeeeeeeeeeeeeeeeee)-8-(8-eeeeee-8-eeeeeeeeeeee)-eeeeeeeee-8-eee (‌888‌); Meeeeee Meeeeeeee:[‌8888‌]

MMMMMMM: Meeeeeeeeeeeeeeeeeee eeeeeeee (MMMM) ee e eeeeeeee eeeee eeeeeeeeee eee ee eee eee eeee eeeeeeee.

M eeee ee eeeeeee eeeeeeeeeeeeee eee eeeeeeee eeee eeeeeeee ee e 8.88 M eeee ee MeMe ee eeeeeee (88.8 eM, 88.8 eeee) ee MeM (8.8 e, 88 eeee) ee eee Me8M (88 eM) ee −88°M. Meeee eeeeeee ee −88°M eee eeee eee eeeeeee eeee 8-(8-eeeeee-8-eeeeeeeeeeee)eeeeeeeee-8-eeeee (8.8 e, 88 eeee) ee Me8M (88 eM) eee eeeeeee eee 88 eee. Mee eeeeeee eee eeee eeeeeee eeee MMM (88 eM), Me8M (8 eM) eeeee, eeeeeeee ee MMMMMMe (8.8 e, 88 eeee) ee MMM/MMMM (88 eM, 8:8), eee eeeeeee eeeeeeeee ee ee. Mee eeeeeee eee eeee eeeeee eeee e eeee ee eeeeee (888 eM) eee M8M (888 eM), eee eeeeeee eeeee eeeeeeeee, eeeee (MeMM8), eee eeeeeeeeeeee ee eeeee. Mee eeeee eeeeeee eee eeeeeeeee ee MMMM (88 eM) eee eee eeeee eeee eeeee eee eeeeeeeee ee eeeeeeeeee eeee eeeeee (8 × 88 eM), eeeeee eeee 88% MeMMM8 (8 × 888 eM), eeeee (MeMM8), eee eeeeeeeeeeee ee eeeee; eeeeeeeeeeee ee eee eeeee eeeeeee eeee ‌888‌; eeeee: 8.8 e (88%); ee 888–888°M/8.88 Meee.

References

Meeeeee Meeeeeeeeee

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