Science of Synthesis

Heaney, H.; Christie, S., Science of Synthesis, (2004) 3, 325.

Conjugate addition reactions where the reactive species is generated by the interaction of an aryl Grignard reagent with a copper(I) catalyst have been reported with a wide range of α,β-unsaturated carbonyl compounds.[‌201‌] Some early examples concentrated on reactions of octalone derivatives.[‌202‌,‌203‌] The addition of phenylmagnesium bromide in the presence of about 8 mol% of copper(I) chloride to 3,4,4a,5,6,7-hexahydronaphthalen-1(2H)-one followed by kinetic protonation of the enolate gives 8-phenyl-trans-3,4,4a,5,6,7,8-octahydronaphthalen-1(2H)-one.[‌204‌] Although the majority of the reports have involved the use of a catalytic amount of a copper(I) salt there are examples where a copper(II) salt is reduced in situ as part of the experimental protocol. For example, the addition of phenylmagnesium bromide to 1,1-dimethyl-4a,5,6,7,8,8a-hexahydronaphthalen-2(1H)-one in the presence of copper(II) acetate resulted in conjugate addition with the phenyl group at position 4 in an equatorial location.[‌205‌] The addition of phenylmagnesium bromide in the presence of 10 mol% of copper(II) acetate to 3,4,4a,5,6,7-hexahydronaphthalen-1(2H)-one followed by protonation of the enolate and base-catalyzed epimerization gives 8-phenyl-cis-octahydronaphthalen-1(2H)-one (‌5‌) in a 72% yield of useable material (‌Scheme 23‌).[‌206‌]

‌Meeeee 88‌ Meeeeeeee ee 8-Meeeee-eee-eeeeeeeeeeeeeeeeeee-8(8M)-eee[‌888‌]

M eeeeeeeeeeee eeee-eeeee eeeeeeeeeee ee e eeeeeee ee eee eeeeeeee 8-eeeeeeeeeeeeeee ‌8‌, [(8M,8M)-(+)-8-eeeeee-8-(8-eeeeee-8-eeeeeeeeeee)eeeeeeeeeeeee eee eee 8M-eeeeee], eeee eeeeeeee eee eeee eeeeeeee eeeee ee. 8 eee% ee eeeeee(M) eeeeee ee eeeeeeee ee eeeeeeeeeee eeee eeeeeeeeeeeeeee eeeeeee (‌Meeeee 88‌).[‌888‌] Me eee eeee eeeee eeee eee eeeeee(M) eeee eeeeeeeee eeeeeeeee eeeeeeee ee (8,8-eeeeeeeeeeeeee)eeeeeeeee eeeeeee ee eeeeeeee-8-eeeee eee ee eeeeeee eee eeeeeee eee eeeee eeeeeeeeeee ee (8-eeeeeeeeee)eeeeeeeee eeeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeeeeeee ee eee Meeeeeee 8-Meeeeeeeeeeeeee eeee Meeeeeee ee Meeeeeee eeee Meeeeeeeeeeeeee Meeeeee Meeeeeeee ee Meeeee(M) Meeeee[‌888‌]

8,8-Meeeeeeeeeeee eeeeeeeeeeeeeee eee eeeee ee e eeeeee ee eeeeeeeeeeee eeeeee eeeeeeeee, e.e. ee eee eeeeeeeee eeeeeeeeee eeeeeeeeee. Meeeeeeee, eeeeeeeee eeeeeeee ee e 8-eeeeeeeeeee eeeeeeeee-8-eeeee ee ee eeeeeeeeeeee eeeeeee eeeeeeee eeeeee ee e eeeeeeeee eeeee ee eeeee eeeeeeeee. Mee eeeeeeee eeeeeee (8-eeeeeee-8-eeeeeeee)eeeeeeeee eeeeeee ee eee eeeeeeee ee 8 eee% ee eeeeee(M) eeeeeeee eee 8-(eeeeeeeeeeeeeee)eeeeeeeee-8-eeeee eeeee eee eeeeeeeee eeeeeeee eeeeeee eeeee ee ‌Meeeee 88‌ ee 88% eeeee.[‌888‌] Meeeeee ee eee eeeeeee eeeeeeeeeeeeeeee ee eeeeee eeeeee, eee eeeeeeee eeee eeeeeeee eeeeeeeeeee eeee eeeeeeeeee eeeeeeeeeeee eeeeeeeeeeeee eeeeeeee. Mee eeee eeeeeee ee eeee eeeeeeeeee ee eee eeeeeeee ee (8-eeeeeee-8-eeeeeeee)eeeeeeeee eeeeeee ee eee eeeeeeee ee 8 eee% ee eeeeee(M) eeeeeeee eee eeeeeeee eee-8-eee-8,8-eeeeee.

‌Meeeee 88‌ Meeeeeeee Meeeeeee ee 8-Meeeeee-8-eeeeeeeeeeeeeeeee Meeeeee eeee 8-(Meeeeeeeeeeeeee)eeeeeeeee-8-eeeee[‌888‌]

Me eeeeeee Meeeeee eeeeeeee eeeeee ee eee eeeeeeee ee eeeeeeeeeeeeeee eeeeeee eeee eeeeeee (8,8-eeeeeeeeeeeeeee)eeeeeeee ee eee eeeeeeee ee 8 eee% ee eeeeee(M) eeeeee. Mee eeeee eeeeeee eeee ee eeeeee eeee eeeeeeee eee eeeeeeeeeeeeee eeeeeeeee. Mee eeeee eeeeeeee eeeee eee eeeeeee eeee eee eeee ee eeee eeeeeeee ee eeeeeeeeeeeee, ee eeeee ee ‌Meeeee 88‌.[‌888‌]

‌Meeeee 88‌ Meeeeeeee Meeeeeee ee ee α,β-Meeeeeeeeee γ,δ-Meeee Meeeeee[‌888‌]

M eeeee eeeeeeee ee eeeeeeeeeeeeeeeeee eeeeeeeee eeeeeeee eeeeeeeee eeeeeeee eeeeeeee ee eeeeeeeee eeee eeeeeee eeeeeeeeeeee eeeeeeee.[‌888‌] Mee eeeeeeeeeeeeeee eeeeeeeee ee e eeeeee ee eeee Meeeeeee eeeeeeee ee (8M)-8-[(8M)-8-eeeeeeeeee-8-eeeee]-8-eeeeee-8,8-eeeeeeeeee-8-eee eeeeeee eeeeeeeeeee ee eee eeeeeeee ee eeeeeeeee eeeeeee ee eee eeeeee(M) eeeeeee–eeeeeeee eeeeeee eeeeeee. Mee MMM eeeeeee ee eee eeeee eeeeeeee eeee eee eeeeeeee ee eeee eee eeeeeeeeeeee. Mee eeeee ee eeeeeee ee eeee eeee eeee eeeee eee eeeeeeeeee eeeeeeee (8,8-eeeeeeeeeeeeee)eeeeeeeee eeeeeee, ee eeeee ee ‌Meeeee 88‌.[‌888‌] Me M-eee eeeeeee eeeeeeeee eeeeeeee ee eee eeeeeee eeeeeee eeee eee eeeeeeee eeeeeeeee (8,8-eeeeeeeeeeeeee)eeeeeeeee eeeeeee eeeeee eeee eee eee eeeeee eeeeee eee eeee ee M eeeeeeeeeeeee. Meee eeeeeeee eeee eee eeeeeeeeeeeee ee eee β-eeeeee eeeeeee eeee Me-eeee eeeeee ee e eeeeee ee eeeeeeeee ee eee Me-eeee ee eee eeeeeeeeee eeeee ee eee eeeeeeeeeeeee eeeeee eeee.

‌Meeeee 88‌ Meeeeeeeeeeeeeeeee Meeeeeeee Meeeeeee ee Meeeee(M)-Meeeeeeee Meee Meeeeeee Meeeeeee Meeeeeeeee ee e Meeeee Meeeee Meeeeeeeeeeee[‌888‌]

Me ee ee eeeeeeee ee eeee eeee eeeeeeeee ee eee eeee eeeeeeeee eeeeeeeee Meeeeeee eeeeeeee eeee eeeee e 8-eeeeeee eeeeeeeeeee eeee eeee eeeeeeee eeeeeeeee eeeeeeee ee eee eeeeeeee ee 8 eeeeeeeeee ee eee eeeeee(M) eeeeeee–eeeeeeee eeeeeee eeeeeee (eee Meeeeee ‌8.8.8.8.8.8‌).

Mee eeeeeeeee eeeeeeee eeeeeeeee ee eeee Meeeeeee eeeeeeee eeee e eeeeee ee α,β-eeeeeeeeeee eeeeee eeee eeeee eeeee eeeeeeeeeeee eeee eeee eeee eeeeeeee. Mee eeeeeeee ee, eee eeeeeee, (8-eeeeeeeeeeee)eeeeeeeee eeeeee eeee 8,8-eeeeeee-8,8:8,8-ee-M-eeeeeeeeeeeeee-M-eeeeeee-eeeee-eeee-8-eeeeee eeeee 8 eee% ee eeeeee(M) eeeeee eeeee eee eeeeeeeee eeeeeeee eeeeeee eeee eeee eeeeeeeeeeeeeeeee ee 88% eeeee.[‌888‌] Mee eeeeeeee eeee eee eeeeeeee eeee e eeeeee ee eeee Meeeeeee eeeeeeee eee eeee eee M-eeeee eeeeeeeeeeeee, eee eeeeeeeeee (8-eeeeeeeeeeee)eeeeeeeee eeeeeee eee 8-eeeeeeeeeeeeee eeeeeee eeee eeeeeeee eee ee eeeee eeee eee eeeee eeeeeeeeee. Meeeeeeee eeeeeeee ee (M)-M-(M)-eee-8-eeeee-8,8-eeeeeeeeeeeeeeeeeeeee eee eeee eeeeeeee ee e eeee eeeee eee eeee eeeeeeeee eeeeeeeeeeeeeeeeeeee eeeee eee eeeeee Meeeeeee eeeeeee ee eee eeeeeeee ee eeeeee(M) eeeeee eeee eeeeeeee eeeeeee ee eee eeeeeee.[‌888‌]

Meeeeeeee eeeeeeee eeeeeeee ee Meeeeeee eeeeeeeeee ee e eeeeeeeeee eeeeee eee eee eeeeeeeeeee eeeeeeeee ee e M—M eeee eeeeeeee ee eeeeee eeee eeeeeeeee. Meee eeeeeeee eee eeee eeee ee e eeeeeeee eeeee eeeeee 8-eeeeeeeeeeeeeeeeeeeeee ee eeeeeee eeee eeeeeeeeeeeeeee eeeeeee ee eee eeeeeeee ee 8.8 eee% ee eeeeee(M) eeeeeeee eeeeeeee ee eeeeeeee eeee eeeeeeeeeeee.[‌888‌] Meeeeeeee ee e eeeee ee eeee Meeeeeee eeeeeeee, eeeeeeee ee e 8:8 eeeeee, eeee eeeeee eeeeeeeeeeeeeeeeeee ee eeeeeee eeeee/eeeeeee ee eee eeeeeeee ee 8 eee% ee eeeeee(M) eeeeee eeee eeeeee ee eeeeeeeeeee eeeeeeeeeee ee eee eeeee 88–88%. Meeeeeee eee eeeeeee eeeee eeee eeeeeeeeeee eeeee eee eeeeeee eeeee ee ‌Meeeee 88‌.[‌888‌] α,β-Meeeeeeeeee eeeeee eee eeeeeee eeee eeee eeee eeeee ee eeee eeee ee eeeeeeeee eeeeeeee eeeeeeeee eeee eee eeee Meeeeeee eeeeeee–eeeeee(M) eeeeee eeeeee.[‌888‌]

‌Meeeee 88‌ Meeeeeeee Meeeeeee ee Meeeeeeeeeeeeee Meeeeee eeee Meeeee 8-Meeeeeeeeeeeeeeeeee eeeeeeee ee Meeeeeeeee eeee Meeeeeeeeee[‌888‌]

Meeeeeeee eeeeeee ee eeeeee eeee eeee eeee eeee ee eeeeeeeeeee eeee eeee Meeeeeee eeeeeeee ee eeeeee eeeeeeeee eeeeeeee ee eeeeeeeeeeee eeeeeee. Meeeeeeeeeeeeee eeeeeee eee (8-eeeeeeeeeeeee)eeeeeeeee eeeeeee ee eee eeeeeeee ee eee eeeeee(M) eeeeeee–eeeeeeee eeeeeee eeeeeee eeeee eeee 8-eeeeeeeeeeeeeee-8M-eeeeeeeee-8-eee, eee eeeeeeeeeeee eee eeee 8M-eeeeeeeee-8-eee eeeeee.[‌888‌] Meeeeeeeeee eeeeeeee eeeeeeeee eeeeeeee eeeeeeeeeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeeee eeeeeee–eeeeee(M) eeeeee (8 eee%) eeee eee eeeeeeee eeeeeee ee eee eeeeeeee eeeeeee eeeeee eeeeeeeeeeeee eee ee eeeee 8-eeeeeee eeeeee.[‌888‌]

Meeeeeeeeeee Meeeeeeee

8-Meeeee-eee-eeeeeeeeeeeeeeeeeee-8(8M)-eee (‌8‌); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee 8,8,8e,8,8,8-eeeeeeeeeeeeeeeeeee-8(8M)-eee (88 e, 888 eeee) eee eeeee Me(MMe)8 (8.88 e, 88 eeee) ee MMM (888 eM) eee eeeee ee e 8.88 M eeee ee MeMeMe (888 eM, 888 eeee) ee Me8M eee eee eeeeeee eee eeee eeeeeee eee 88 e. Mee eeeeeeee eee eeeeeeee eeee ee MM8/MM8Me eee eee eeeeeee eeeee eeeeeeeee eeee Me8M. Meeeeeeeeeeee ee eee eeeee eeeeeee eee eeeeeee eee eeeee eeeeeeeeee MeMMe [Me (88 e) ee MeMM (888 eM)] eeeee eeeeee eee 88 e, eeeeeeee ee eee eeeeeeee ee M8M eee eeeeeeeeee eeee Me8M. Meeeeeeeeee ee eee eeeee eeee eee eeeeeeeeeeeeeeee (eeeeee) eeee ‌8‌; eeeee: 88.8 e (88%); ee 88–88°M. Me eeeeeeeeee 8% ee eeeeeee eee eeeeeeee eeee eee eeeeee eeeeeee eee eeeeeeeeeeeeee ee eee eeeeeee ee eeeeeee (eeeeeeee eeeee MM) eeee ee eeeeeeeeee 8%.

8-Meeeeeeeeeeeeee ‌8‌; Meeeeee Meeeeeeee:[‌888‌]

M eeee ee MeMeMe, eeeeeeee eeee MeMe (88 e, 8.88 eee) eee Me eeeeeee (88 e, 8.88 eee) ee Me8M (888 eM) eee eeeeee ee −88°M eee MeM (8 e, 88 eeee) eee eeeee. Mee eeeeeee eee eeee ee −88°M eee 88 eee eeeeee e eeee ee (8M)-8-eeeeee-8-(8-eeeeeeeeeeeeeeee)eeeeeeeeeeeee [(M)(−)-eeeeeeee] (88 e, 8.88 eee) ee Me8M (888 eM) eee eeeee eeeeeeee. Mee eeeeeeeee eeeeeee eee eeeeeee ee eeee ee ee eee eeeeeee ee ee eee e eeeeeee 88 e eeeeee eeeee eeeeee ee ee eee eeee eee eeeeeeee eeee M8M (88 eM) eee eeee e eeee ee MM8Me (88 e) ee M8M (888 eM) eee eeeee MMe (88 eM). Mee eeeeeee eeeee eee eeeeeeeee eee eeeeeeeee eeee Me8M (8 × 88 eM). Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee e eee. ee eeee ee MeMMM8 eee eeeee (MeMM8). Meeeeeeeeee ee eee eeeeeee eee eeeeeeeeeeee ee eee eeeeeee eeee eee eeeeeeee 8-eeeeeeeeeeeeeee ‌8‌ (8:8 ee MMMM eee 88M MMM eeeeeeeeeeee); eeeee: 88 e (88%); ee 88–88°M/8.88 Meee.

References

Meeeeee Meeeeeeeeee

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