Cobalt‐Catalyzed Reductive Allylation of Alkyl Halides with Allylic Acetates or Carbonates

Abstract

Transition-metal-catalyzed allylic alkylations, using a broad range of metal complexes, have been intensively studied because of their potential applications in the synthesis of new olefinic compounds in particular for total synthesis.[1] Soft nucleophiles are usually used in Pd-, [1] Mo-, [2] Ir-, [3] Ru-, [4] Rh-, [5] Pt-, [6] and even Fe-catalyzed [7] allylic substitutions. Ni, [8] Co, [9] and Cu [10] catalysts allow the use of hard nucleophiles such as alkylzinc or Grignard reagents, but limited functional group compatibility and/or poor regioselectivity can be observed if the system is not designed carefully. To avoid handling the air-and moisture-sensitive organomagnesium and organozinc reagents, straightforward procedures, which do not require organometallic reagents, are highly desirable and many have now been developed. [11] To the best of our knowledge, direct transition-metal-catalyzed alkyl-allyl cross-couplings using in situ generated catalytic organometallic reagents are still unknown. However, a few years ago, we reported a related Co-catalyzed coupling reaction of aryl halides with allylic acetates; [12] these reactions in the presence of an appropriate reducing reagent, gave allylaromatic compounds. Such allylic carboxylates, whilst less reactive than allyl halides, are much more environmentally friendly.Given our previous experience with the direct Cocatalyzed functionalization, including alkylation, [11c] of aryl halides [13] we were interested to take the chemistry further, and herein we report a new and general method for direct reductive cross-coupling of allylic acetates with alkyl halides using a CoBr 2 /Mn system with an acetonitrile/pyridine solvent mixture. The approach accommodates a variety of simple and functionalized alkyl halides and substituted allylic compounds and is experimentally straightforward. Indeed it uses off-theshelf reagents without any particular precautions against air and moisture. First, we investigated the use of the readily available yet poorly reactive ethyl 4-bromobutanoate with a simple allyl acetate as the electrophile. The major challenge here lies in promoting cross-coupling rather than the formation of reduction and homocoupling products.

Cobalt‐Catalyzed C−C Homocoupling

“…We identified that a combination of CoBr 2 /Mn/pyridine in CH 3 CN, as previously reported for the allyl-alkyl cross-coupling reaction, [13] afforded the desired coupling product in 84% yield (Table 1, entry 1). Without pyridine, the reduction product was rapidly the main product (Table 1, entry 2).…”

“…Alkyl bromides bearing electron-donating groups and electron-withdrawing groups, such as ester ( Table 2, entry 9), ketal (Table 2, entry 13) efficiently reacted. Interestingly, whereas isoindole-1,3-dione and ketone groups were not tolerated in the cobalt-catalyzed allyl-alkyl cross-coupling reactions, [13] they provided moderate to good yields in this homocoupling reaction (Table 2, entries 10 and 16). Benzyl chloride, which is more reactive, could also be used in this reaction (Table 2, entryies 14 and 15).…”

Nickel-catalyzed dimerization of pyrrolidinoindoline scaffolds: systematic access to chimonanthines, folicanthines and (+)-WIN 64821

“…20 All reactions were performed under a nitrogen atmosphere unless otherwise specified. NMR spectra were recorded on JEOL α400, JNM-ECX 400 ( 1 H/400 MHz, 13 C/100 MHz), and Bulker VSP 500 ( 1 H/500 MHz, 13 The medium pressure liquid chromatography (MPLC) purifications were performed on a YAMAZEN YFLC-AI-580. Where necessary, solvents were distilled from appropriate drying agents prior to use.…”

“…The residue was purified by silica-gel column chromatography to afford (+)-WIN 64821 (6) (33.2 mg, 0.050 mmol, 59%). The NMR spectra were identical to the 13 …”

Nickel-Catalyzed Reductive Couplings

“…While most transformations based on activated alkyl electrophiles emphasize C(sp 3 )-C(sp 2 ) bond forming methods (see Sects. 2.2-2.5), the cross-coupling of allylic acetates (or carbonates) with unactivated alkyl halides represents the only example for the construction of hetero C(sp 3 )-C(sp 3 ) bonds utilizing activated alkyl electrophiles [36][37][38].…”