Intermolecular Hydropyridylation of Unactivated Alkenes

Abstract

A general method for the hydropyridylation of unactivated alkenes is described. The transformation connects metal-mediated hydrogen atom transfer to alkenes and Minisci addition reactions. The reaction proceeds under mild conditions with high site-selectivities and allows for the construction of tertiary and quaternary centers from simple alkene starting materials.

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

“…Sulfonyl oximes 6a and 6b [32] afforded the carbon–carbon coupled products 4j and 4k in 60% and 48% yields, respectively (Table 1, entries 11 and 12, respectively). Recently, our laboratory reported a formal intermolecular hydroheteroarylation using N- methoxy heteroarenium salts by Co(acac) 2 -mediated HAT [33–34]. In the original reports, 36 discrete unactivated alkenes were coupled with 38 different heteroarenium salts under mild conditions [33–34].…”

“…Recently, our laboratory reported a formal intermolecular hydroheteroarylation using N- methoxy heteroarenium salts by Co(acac) 2 -mediated HAT [33–34]. In the original reports, 36 discrete unactivated alkenes were coupled with 38 different heteroarenium salts under mild conditions [33–34]. A representative example comprises the coupling of methallyl p -methoxybenzoate ( 3a ) with N -methoxypyridinium methyl sulfate ( 6c ) to form the hydropyridylation product 4l in 66% yield and as a 4.7:1 ratio of regioisomers (Table 1, entry 13).…”

“…Additionally, methods to achieve carbon–carbon bond formation to alkenes by HAT have been developed (e.g., reductive coupling [22–28], formal hydromethylation [29], cycloisomerization [8,30–31], hydrooximation [32], hydroheteroarylation [28,33–35], hydroarylation [36–38], and cross-coupling [37]). Many of these transformations have found applications in synthesis [6,39–47].…”

Direct Functionalization of C−H Bonds by Iron, Nickel, and Cobalt Catalysis

“…The group of Herzon reported the hydropyridylation of unactivated alkenes using substituted N ‐methoxypyridinium compounds (e.g., 212 ) as starting material. Again, simple [Co(acac) 2 ] was used as catalyst but as additives tert ‐butylhydroperoxide (TBHP) and Et 3 SiH (to reduce the product to the pyridine products) were required . The reaction can also be considered as an alkylation of the pyridinium species, which took place regioselectively in position‐4 to give 213 (Scheme ).…”

Visible‐Light‐Induced ortho‐Selective Migration on Pyridyl Ring: Trifluoromethylative Pyridylation of Unactivated Alkenes

“…Thep otential of N-alkoxypyridinium salts has been demonstrated in synthesis as easily accessible,v ersatile,a nd bench-stable pyridine surrogates. [7][8][9] Fore xample,c obaltmediated alkene functionalization [8] and ar emote C(sp 3 )ÀH pyridylation strategy by 1,5-hydrogen atom transfer [9] were successfully achieved using N-alkoxyheteroareniums alts to afford various alkylpyridine products.U nfortunately,o nly modest regioselectivity (C2 vs.C 4) has been observed in the trapping of N-alkoxypyridinium salts with secondary alkyl radicals while tertiary alkyl radicals provide para(C4)-selective pyridyl products (Scheme 1b).…”