Ketone Formation via Mild Nickel-Catalyzed Reductive Coupling of Alkyl Halides with Aryl Acid Chlorides

Abstract

The present work highlights unprecedented Ni-catalyzed reductive coupling of unactivated alkyl iodides with aryl acid chlorides to efficiently generate alkyl aryl ketones under mild conditions.

Reductive Cross‐Coupling Reactions between Two Electrophiles

“…The presence of ortho ‐substituents and electron‐withdrawing groups results in decreased yields. A radical mechanism was postulated 42…”

Nickel-Catalyzed Reductive Couplings

“…The coupling protocols are suited for primary and secondary alkyl halides with acid derivatives, including acid chlorides, anhydrides, and in situ activated acids in the presence of Boc 2 O and MgCl 2 [63][64][65][66][67][68]. Although initial development was centered on primary and secondary alkyl iodides, finely tuning the reaction parameters satisfied alkyl bromides.…”

Nickel‐Catalyzed Synthesis of Ketones from Alkyl Halides and Acid Chlorides: Preparation of Ethyl 4‐Oxododecanoate

“…2 While both of these protocols are effective, the organometallic reagents can be limiting with complex, functionalized molecules. More recently, cross-coupling methods based upon the 14 The product exhibited the following physical properties: yellow liquid. 1 H NMR (400 MHz, CDC1 3 ) δ: 0.88 (t, J = 6.5 Hz, 3H), 1.20-1.23 (m, 13H), 1.59 (t, J = 7.0 Hz, 2H), 2.44 (t, J = 7.5 Hz, 2H), 2.57 (t, J = 6.7 Hz, 2H), 2.71 (t, J = 6.5 Hz, 2H), 4.14 (q, J = 7.2 Hz, 2H).…”

“…For example, Gong reported modified conditions that enable coupling with anhydrides 12 as well as the use of tertiary alkyl halides, 13 aryl acid chlorides, 14 and methyl p-toluenesulfonate ester. 15 It is also important to note that one-pot protocols for the generation and coupling of acid chlorides 14 and anhyrides 13 have been reported.…”