Reductive Decarboxylative Alkynylation of N‐Hydroxyphthalimide Esters with Bromoalkynes

Abstract

An ew method for the synthesis of terminal and internal alkynes from the nickel-catalyzed decarboxylative coupling of N-hydroxyphthalimide esters and bromoalkynes is presented. This reductive cross-electrophile coupling is the first to use aC (sp)ÀXe lectrophile,a nd appears to proceed via an alkynylnickel intermediate.T he internal alkyne products are obtained in yields of 41-95 %w ithout the need for ap hotocatalyst, light, or as trong oxidant. The reaction displays abroad scope of carboxylicacid and alkyne coupling partners, and can tolerate an array of functional groups,i ncluding carbamate NH, halogen, nitrile,o lefin, ketone,a nd ester moieties.M echanistic studies suggest that this process does not involve an alkynylmanganese reagent and instead proceeds through nickel-mediated bond formation.

Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

“…Based on our investigations and related studies, 14,60,64 a tentative mechanism is proposed in Fig. 5.…”

“…Addition of TMSCl (known to activate the Mn(0) surface 66 ) to the reaction system was somewhat detrimental (Table 1, entry 7), whereas ZnCl2 or MgBr2 additives 67 also reduced the yield of 4a (Table 1, entries 8 and 9). Considering the previously reported role of lithium salts in minimizing diyne formation, 14 we found that the use of LiBr (0.5 equiv.) indeed improved results, affording 4a in 76% yield (73% isolated; Table 1, entry 10).…”

“…Starting from an in situ-generated Ni(0) species i (e.g. from reduction of the Ni(II) precatalyst 14,64 , oxidative addition with bromoalkyne 2 followed by single-electron reduction in the presene of Mn gives rise to an alkynylnickel(I) species iii. At this stage, a second molecule of 2 could potentially react with iii to give dialkynylnickel(III) vii that subsequently reductively eliminates to afford the undesired diyne side product 7.…”

“…Our motivation to pursue this approach is twofold: (1) The greater variety of N-(acyloxy)phthalimides accessible from aliphatic carboxylic acids (vs. alkyl halides) means that diverse aliphatic units (tertiary, secondary, primary) can be incorporated; (2) The ability of NHPI esters to promote challenging alkylalkynylations in which alkyl halides fail to deliver, by minimizing rampant undesired pathways arising from homocoupling [63][64] and cross-coupling 14,16 of the alkynyl halide and NHPI ester reactants, as well as alkyne cyclotrimerization 65 (see Fig. 4 for further discussion).…”

Chemoselective Union of Olefins, Organohalides, and Redox-Active Esters Enables Regioselective Alkene Dialkylation

“…As shown in Scheme 7b, the appropriate combination of catalytic reductive dialkylation of unsaturated amides and catalytic decarboxylative cross-coupling can enable multiple carbon-carbon linkages to be installed in a regioselective fashion, thus providing an expedient avenue to create complexity and diversity for compound library synthesis. To further illustrate this versatility, N-(acyloxy)phthalimides derived from dialkylation adducts were subjected to established decarboxylative transformations 13c, 17,18 (furnishing C(sp)C(sp 3 ), C(sp 2 )C(sp 3 ) and C(sp 3 )C(sp 3 ) bonds) to give 15ac in 8186 % yield (Scheme 7b).…”