Science of Synthesis

Sellars, J. D., Science of Synthesis Knowledge Updates, (2014) 1, 408.

There are an array of commercially available acid chlorides and anhydrides; however, being able to start from a carboxylic acid allows for much greater substrate scope. As seen in Section ‌26.8.4.1.1.1.5‌, carboxylic acid substrates can be converted in situ into a more reactive acylating agent that then undergoes acylation to produce aryl ketones. However, direct activation of carboxylic acids is possible using a heterogeneous mixture of phosphorus pentoxide and alumina (50% w/w), in 1-butyl-3-methylimidazolium bis(trifluoro­methanesulfonyl)amide/trifluoromethanesulfonimide ([bmim]NTf2/Tf2NH; 1:1) or 1-butyl-3-methylimidazolium tetrafluoroborate/boron trifluoride diethyl ether complex ([bmim]BF4/BF3•OEt2; 2:1) under microwave irradiation. Both methods provide access to aryl ketones in good yield.[‌59‌,‌60‌] Whilst lanthanides, particularly the trifluoromethanesulfonates, have been heavily exploited with acid chlorides and anhydrides (cf. Section ‌26.8.4.1.1.1.3‌), the same cannot be said for carboxylic acids. A screening array of lanthanide trifluoromethanesulfonates has revealed that very high temperatures (250 °C) and long reaction times (>12 h) are required to achieve reasonable levels of conversion into aryl ketones. However, on switching to the more Lewis acidic lanthanide bis(trifluoro­methanesulfonyl)amide salts, an improved yield and conversion are observed.[‌61‌] Similar to the activated carboxylic acids, supported reagents have been utilized with carboxylic acids. Graphite in the presence of 4-toluenesulfonic acid (1:0.1) provides a catalyst system for the conversion of electron-rich arenes and alkane- or arenecarboxylic acids into ketones ‌10‌ (‌Scheme 16‌).[‌62‌]

‌Meeeee 88‌ Meeeeee eeee Meeeeeee-Meee Meeeee eee Meeeeeeeee Meeee[‌88‌]

Meeeeeeeee eeeeeeeee ee eeeeee eee eee eeee eeee eeeeeeee ee eeeeeee eeeeee eeee eee eeeeeeeeeeeee eeee eeeeeee ‌88‌ ee eeeeeeee eeee eeeee- eee eeeeeeeeeeeeeeee eeeee (‌Meeeee 88‌).[‌88‌] Meeeee eee eee eeee eeee eeee ee e eeeeeee eee eeeeeeee eeeeeeeeeee eee eeeeeeee ee eee eeeeeeeeee ee eeee eeeeeee ee eeee eeeeee.[‌88‌] Meeeeeeeeee, e eeeee ee eeeeeeee (M-M, M-eeee, M-M, M-MMM-8) eeee eeee eeeeeeee ee eee eeeeeeee ee eeeeeeee-eeee eeeeee eeee eeee eeeee- eee eeeeeeeeeeeeeeee eeeee.[‌88‌]

‌Meeeee 88‌ Meeeeee–Meeeee Meeeeeeee Meeeeeee ee Meeee-Meeeeeeee Meeeeeeeee Meeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

Meeeeeee eeeee eeeeeeeee eeeeeeee eee eeeeeeeee eeee eeeeeeeeee eeeee, eeeee eee eeee eeeeeeee ee Meøeeeee eeee eeeeeeeee eeeeeeeee. Meeeeeeeeeeeee eeee eee eeee eeeeeeee ee eee eeeeee eeeeeeeee ee eeeeeeeeeeeeeeeeee, eee ee eeeeeee e eeeeeee ee eeeee- eee eeeeeeeeeeeee eeeee eeeeeeeee eeeeeeeeeee.[‌88‌,‌88‌] Meeee eeeeeeeeee eeeee (e.e., M8MM88M88, M8MMe88M, eee M8MeM88M88) eeee eeee eeeeeeeeeeee eeeeeeeee eeeeeeee ee eee Meeeeee–Meeeee eeeeeeeee. Meeeeee eeeeee ee eeeeeeee eeeeeeeeee ee eeeeeeeee ee eeeeee eee eeeeeee eeee eeeeee eeee eeee eeeeeeeeeee (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeeeeeeeee Meeeeeeeee ee Meeeeeeeee Meeee[‌88‌]

‌Meeeeeeeeee 88‌

e Meeeeeeeeee eee eee eeeee eeeeeee eeeee.

Meeeeeeeeeee Meeeeeeee

Meeeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

Mee eeeee (8 eeee) eee eeeeeeeeee eeee (8 eeee) eeee eeeee ee e eeeeeee ee eeeeeeee (MMM Me. 8888–88–8; eeee eeeeee eeeee eeee, eeee Meeee; 8.8 e, 88 eeee) eee eeeee MeMM (88 ee, 8.88 eeee) ee 88 °M ee ee eee eeee. Mee eeeeeee eee eeee ee 88 °M eeeee eeeee eeeeeee eeee e eeeeeeeeee eeeeeee eee eee eeee eeeeeeee ee eeeeeeee eee eeeeeeee. Mee eeeee eeee (eeeeeeee) eee eeee eeeeeeeee eeee MeMMe (88 eM) eee eee MeMMe eeeeeee eee eeeeee eeee ee MeMMM8, eeeee (Me8MM8), eee eeeeeeeeeeee ee eeee eee eeeeeeeeeee eeee eeeeeee.

8-(8-Meeeeeeeeee)-8-(8-eeeee)eeeeeeee (‌88‌, Me8 = 8-Mee); Meeeeee Meeeeeeee:[‌88‌]

Me e eeeeeee ee (8-eeeeeeeeeee)eeeeee eeee (8.88 e, 8.8 eeee) eee eeeeeee (8 eM) eee eeeee M8M8/eeeeee eee (8.8 e), eee eee eeeeeee eee eeeeeee eeeee eeeeee eeeeeeeeee eee 8 e. Meeee eee eeeeeee eee eeee eeeeee, ee eee eeeeeee eeee MeMMe (88 eM) eee eeeeeeee eeeee eeeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeeee eeee MeMMe (8 × 88 eM) eee eee eeeeeeeee eeeeeee eeeeee eeee eeeeee eeee 88% ee MeMMM8 eee eeee eeeee (Me8MM8). Mee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee ee eeee eee eeeeeee; eeeee: 88%.

Meeeee-8,88-eeeeeee (‌88‌, M = M=M); Meeeeee Meeeeeeee:[‌88‌]

8-Meeeeeeeeeeeee eeee (88 eeee), M8MeM88M88 (8 eeee), eee eeeeeeeeeeeee (88 eM) eeee eeeeeee eeee e 88-eM eeeee eeeeeeee eeee e eeeee eeeeeeeeee eee eeeeee eeeeeeeee. Mee eeeeeee eee eeeeee ee eeeeee eee eeeeeeeeee eeeee ee eeeeeee M8M eee eeeeeeeee (ee. 8–88 e). Mee eeeeeee eee eeee eeeeee, eeeeeeee, eee eeeeee eeee MMMe8 eee MeMMe. Mee eeeeeee eeeeee eeee eeeeeeee eee eeee eeeeee eeeeeee e eee ee Meeeee. Mee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee); eeeee: 88%.

References