Science of Synthesis

Landais, Y.; Vincent, J. M., Science of Synthesis, (2005) 26, 662.

Addition of organometallic reagents such as Grignard, cuprates, and organolithium to 1,2-diacyl precursors provides a straightforward route to 1,2-diketones. Oxalyl chloride is the simplest of these precursors and reacts efficiently with Grignard reagents in the presence of 1 equivalent of copper(I) bromide and, importantly, 2 equivalents of lithium bromide (‌Scheme 20‌).[‌50‌] In the absence of lithium bromide, the coupling reaction results in low conversion and a mixture of dione ‌70‌, a ketone, and a large amount of the homocoupling product results. With alkynyl precursors ‌71‌, good yields of diones ‌73‌ are obtained by addition of a solution of lithium acetylide to a suspension of 1 equivalent of copper(I) bromide and 2 equivalents of lithium bromide.[‌51‌] Better results are observed using this one-pot procedure, which generates the copper acetylide (e.g., ‌72‌) in situ, than when the freshly prepared copper acetylide is used. This suggests that lithium acetylides are more readily transmetalated by copper bromide than their magnesium counterparts, leading to a better transfer of the organic moiety from copper to oxalyl chloride. This cross-coupling reaction is thus a simple, general, and high yielding process giving access to symmetrical aryl-, heteroaryl-, and alkyl-substituted 1,2-diketones in one step from oxalyl chloride. The reaction proceeds at 0°C for aryl and alkynyl Grignard reagents and at −78°C for their alkyl counterparts. Other organometallics such as aryltrimethylsilanes react with oxalyl chloride affording 1,2-diketones in good yields.[‌52‌]

‌Meeeee 88‌ Meeeeeeeeee 8,8-Meeeeeeee eeeeeee Meeee Meeeeeee ee Meeeeeeeeeeeee Meeeeeee eeee Meeeee Meeeeeee[‌88‌,‌88‌]

Meeeeeeeeeeee 8,8-eeeeeeeee eee eeeeeeee eeeee eeee eeeeeeee ee eeeeeee eeeee ee eeeee ee eee eeeeeeeee ee eee(eeeeee) ‌88‌ eeee eee eeeeeeeee eeeeee eeeeeeeeee ‌88‌ eee ‌88‌ (‌Meeeee 88‌).[‌88‌] Mee eeeee eeeeeeee ee ee eeeeeeeee ee ‌88‌ eeee eeeeee eeeeeeee, eeeee ee eeee eeeeeeee ee eee eeeee eeeeeeee ee eee eeee eeeee ee eeeeee ‌88‌ eeee eeee eeeeeeee ‌88‌. Me eeeeeeeee eeeee ee ‌88‌ ee eeee eeeeeeee eeeee eeee eeeeeeee.

‌Meeeee 88‌ Me Meeeeeeeeeeee 8,8-Meeeeeee eeeeeee Meeee Meeeeeee ee ee Meeeeeeeeeeeee Meeeeee eeee Meeeee Meeeeeee[‌88‌]

Meeeeeee ee 8,8-eeeeeeee eeee eeeeeeeeeeeeee eeeeeeee eeee eeeee ee 8,8-eeeeeeeee, eeeeeeeee ee eeee eeeeee. Meeeeeeee ee eee eeeeeeeeeeee ee eee eeeee eeeeee, ee ee eeeeeeee ee eeeeeee eeeeeeeeeee ee eeee ee eeeeeeeeeeeee 8,8-eeeeeeeee. Meeeeeee ee 8 eeeeeeeeeee ee eeee Meeeeeee eeeeeeee eeee 8,8-ee(8M-eeeeeeee-8-ee)eeeeee-8,8-eeeee (‌88‌) eeee eeeeeee eeeeeeeeeee eeeeee-eeeeeeeeee 8,8-eeeeeeeee ‌88‌ ee 88–88% eeeee, eeeeeeeee e eee-eeee eeeeeee (‌Meeeee 88‌).[‌88‌] Meeeeeeee, eeeeeeee eeeeeee eeeeeeeeeee eeeeeeee eee Meeeeee-eeee M,M′-eeeeeeeee-M,M′-eeeeeeeeeeeeeee (‌88‌) eeeee eee eeeeeeeeeeeee eeeeeeeeeee 8,8-eeeeeeeee ‌88‌ ee eeeeeeee ee eeee eeeeee (‌Meeeee 88‌).[‌88‌] Mee eeeeeeeee ee e eeeeee eeeeeee eeeeeeeeeeee eeee ‌88‌, eeeee eee eeeeeeeeeeee eeeeee eeeeeeee eeeeeee eeeeeeeee. Meeeeeeeeee eeeeeeee ee eeeeeeeeeeeeeee ee eee eeeeeeeeeee eeeeeee eeeeee eeeeee eeee eee Meeeeeee eeeeeeee. Meeeeeee eeee eeeeeeeeeeee eee eee eeeeeeee ee eee eeeeeeeeeeee. Mee eeee eeeeee eee eeeeeeee eeeee 88–88 eeeee, eeeeeeeeee ee eee eeeeeeee eeeeeeeeeee ee eee eee-eeeeeeee eeeeeeeeeeee eeeeee eeee eeeeeeee ee 8 eeeeeeeeeee ee eeeeeeeeeeeee eeeeeee ee ‌88‌. Meeeeee, eeeeeee ee eee eeeee ee eee eeeeeeee eeee eeee eeeeeeeeeeee eeeeeeeeeeee eeee eeeeeeee eeeeee, eeeee eeeeeeeee eeeeeeeeeeeee eeee eeee e eeeee ee eee eeeeeee 8,8-eeeeeeeee.

‌Meeeee 88‌ Meeeeeeeeee 8,8-Meeeeeeee eeeeeee Meeeeeee ee Meeeeeeeeeeeee Meeeeeee eeee 8,8-Meeeeeee[‌88‌,‌88‌]

Meeeeeeee ee eeee eeeeeeeeeee ee eee eeeeeeeee ee eeeeeeeeeeeee eeee eee eeeeeeeee 8,8-eeeeeeeee ee eee eeeeeeeeeeeeeee. Meeeeeeeeee eeeeeeee ee eee eeeeeeeee eeeeeeeeeeeeee eeeeeeee ee 8,8-eeeeeeee eeeee eeee-eeeeeee eee eeeeee eee eeeee eeeeeee ee eee eeeeeee 8,8-eeeeeeeee. Meeeeeeeeee eeeeeeee ee eee eeeee eeee eeeeeeeeeeeee eeeeeee. Meeeeee, eeeeeeeeee eeeeeeee ee eee eeeeeeeee eeeeeeeeeeeee eeeeeeee eeee eeeeee, eeeeee eeeeee ­eeeeeeeeee eeeeeeee eeeee eeeeeeeeeee 8,8-eeeeee ee eeeeeeeee eeeeee (‌Meeeee 88‌).[‌88‌] 8,8-Me­eeeeeeeeeeeeeeee-8,8-eeeee (‌88‌) ee eeeeeee eeeeeeee eeeeeee eeeeeeeeeeee ee ee eeeeeeeee eeeeee ee M,M′-eeeeeeeeeeeeeeeeeeeeeee eee eeeeeee eeeeeee ee eeeeeee eeeee ee eeeeee-8-ee. Meeeeee eeeeeeee ee 8 eeeeeeeeeee ee ee eeeeeeeeeeeee eeeeeee eeee 8,8-eeeeeeeeeeeeeeeeee-8,8-eeeee (‌88‌) ee eeeeeeeeeeeeeee eeeee ee eeeeeeeeeee 8,8-eeeeeeeee ‌88‌ ee eeee eeeee. Meeeeeeee ee eeeeeeeeeeeeeee eee eeeeeeeee eeeeee eeee ee eeeeeee eeeee eee ee eee eee eeeeeeeeee ee 8,8-eeeeeeeeeeeeeeeeee-8,8-eeeee (‌88‌) ee eeee eeeeeee. Meeeeeee eeeeeeee eee eeee ee eeee ee eeee eeeeeee eee eeeeeee eee eeeeeee eeeeeeee eeee eeeeeeee eeeee eeeeee. Mee eeeeeeee eeeeee eeeeeeee ee eeeeeee ee eeee eeeee eeeee ee eee eeeee eee-eeeeeeee eeee eeeeeeeee ee eee eeeeee eeeeeee. Meeeeeeeeee ee eeee eeeeeeee ee eee eeeeeeeeeee ee eeeeeeeeeeeee 8,8-eeeeeeeee eee ee eeeeeeeeeeeee eeeeeee eeeee 8,8-eeeeeeeeeeeeeeeeee-8,8-eeeee (‌88‌), eeeee eee ee eee eeee eeeeeeeeee ee eeeeeee eeeeeeee. Meeeeee, eeee-eeeee 8,8-eeeeeeeeeeeeeeeee-8,8-eeeee (‌88‌), eeeeeee ee eeeeeee eeeee eee eeeeeeeeeeeeeee eeeee ee eeeeeeeee eeeee ee eeeeeeeeeeeee 8,8-eeeeeeee ‌88‌. Meeeee eeeeeeeee eeeeee eee M,M′-eeeeeeeeeeeeeeeeeeeeee ee ee eeeeeeee (eeeeeee eeeeeeeee eeeee: 88%). Me eeeeeee, eeee eeeeee ee ee eeeeeee eee eee ee eeeeeeeeee ee eee eeeeeeeeeee ee eeee eeeeeeeeeee eee eeeeeeeeeeeee 8,8-eeeeeeeee eeeeeeee eeee eee eeee eeeeee eeeeeee.

‌Meeeee 88‌ Meeeeeeeeee eee Meeeeeeeeeeee 8,8-Meeeeeeee eeeeeee Meeeeeee ee Meeeeeeeeeeeee Meeeeeee eeee 8,8-Meeeeeeeeeeeeeeee-8,8-eeeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

8,8-Me(8-eeeeeee)eeeeee-8,8-eeeee (‌88‌, M8 = 8-Meeeeee); Meeeeee Meeeeeeee:[‌88‌]

M MMM eeee ee eeeee MeMe (88 eM, 88.88 eeee) eee eeeee ee ee, eeeee M8, ee e eeeeeee eeeeeeeeee ee MeMe (8.88 e, 8.88 eeee) ee MMM (88 eM). Mee eeeeeeeee eeeeeee eee eeeeeee ee eee eeee eeeeeeeeeee eeeee ee eeeeee eeeeeeeeeee, eeee eeeeee ee 8°M. M eeeeeee eeeeeeee eeee ee 8.88 M 8-eeeeeeeeeeeeeeee eeeeeee ee MMM (8.8 eM, 8.88 eeee) eee eeee eeeeee eeeeeeee ee MMM (88 eM, 8.88 eeee) eeee eeeeeee eeeee ee eee eeeeeee eeee ee eeeee. Mee eeeeeee eee eeeeeee ee 8°M eee 88 eee, eeeeeeee eeee eee. ee MM8Me, eee eeeeeeeee eeee MeMMe. Mee eeeeeee eeeeeeee eeee eeeee (MeMM8) eee eeeeeeeeeeee eeeee eeeeee ee eeeeee e eeeeeee eeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (eeeeee eee, eeeeeeeee eeeee/MeMMe 88:8) ee eeee e eeeeee eeeee; eeeee: 888 ee (88%); ee 88–88°M.

8-Meeeee-8-(8,8,8,8-eeeeeeeeee-8M,8M-eeeee[ee]eeeeeeeeee-8-ee)eeeeee-8,8-eeeee (‌88‌, M8 = 8,8,8,8-Meeeeeeeee-8M,8M-eeeee[ee]eeeeeeeeee-8-ee); Meeeeee Meeeeeeee:[‌88‌]

8-Meeee-8,8,8,8-eeeeeeeeee-8M,8M-eeeee[ee]eeeeeeeeeee (8-eeeeeeeeeeeeeee; 8.8 e, 88.8 eeee) ee eee MMM (88 eM) eee eeeeeee eeee 8.8 M MeMe ee eeeeee (8 eM, 88.8 eeee) ee −88°M. Mee eee eeeeeeeeee eee eeeeeee ee −88°M eee 8 e. Meeeee eeee eeee, 8.88 M MeMe ee eeeeeeeeeee/Me8M (8 eM, 8.88 eeee) eee eeeee eeee eeeeee (88 eee) ee 8°M ee e eeee ee 8,8-eeeeeeeeeeeeeeeee-8,8-eeeee (‌88‌; 8.88 e, 8.88 eeee) ee eee MMM (88 eM). Meee eeeeeee eee eeee eeeeeee eee 8 e. Mee eeee eeeeee ee 8,8,8,8-eeeeeeeeee-8M,8M-eeeee[ee]eeeeeeeeee-8-eeeeeeeee eee eeee eeeeeeeeeee eeeee eeeeeeee M8 eeeeeeee eeeeeee e eeeeeee ee eee 8,8-eeeeeeeeeeeeeeeee-8,8-eeeee/MeMe eeeeeee ee eeee e eeeeeeee eeee eeeee eee eeeeeee ee 8°M eee 8 e eee ee ee eee 8 e. Mee eeeeeee eeee eee eeeeeeeeee eeee eee. MM8Me (888 eM) eee eeeeeeeee eeee MM8Me8 (8 ×). Mee eeeeeeeee eeeee eeeeeeee ee eeee eeeee eee eeeeeeee eee eeeee ee eeeee ee eeee eee M,M′-eeeeeeeeeeeeeeeeeeeeee eeeeeeeeeeeee eeee; eeeee: 8.88 e (88%). Mee eeeeee eeeeeee eeeeeeee eee eeeeeeeeee ee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, MM8Me8) ee eeeeee eeeeee eeeeeeee; eeeee: 8.8 e (88%); ee 888–888°M; 88M MMM (MMMe8, δ): 888.8 (M=M), 888.8 (M=M).

References

Meeeeee Meeeeeeeeee

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