Iridium-Catalyzed Regioselective Silylation of Secondary Alkyl C–H Bonds for the Synthesis of 1,3-Diols

We report Ir-catalyzed intra­molecular silyl­ation of secondary alkyl C–H bonds. (Hydrido)­silyl ethers, generated in situ by de­hydro­gen­ative coupling of a tertiary or conformationally restricted secondary alcohol with diethyl­silane, undergo regio­selective silyl­ation at a secondary C–H bond γ to the hydroxyl group. Oxidation of the resulting oxa­silol­anes in the same vessel generates 1,3-diols. This method provides a strategy to synthesize 1,3-diols through a hydroxyl-directed, functionalization of secondary alkyl C–H bonds. Mechanistic studies suggest that the C–H bond cleavage is the turnover-limiting step of the catalytic cycle. This silyl­ation of secondary C–H bonds is only 40–50 times slower than the analogous silyl­ation of primary C–H bonds

Ortho Arylation of Acetanilides via Pd(II)-Catalyzed C−H Functionalization

A remarkable transformation to realize ortho arylation of acetanilides via Pd(II)-catalyzed C−H functionalization with trialkoxyarylsinaes was demonstrated

Iridium-Catalyzed Regioselective Silylation of Secondary Alkyl C–H Bonds for the Synthesis of 1,3-Diols

We report Ir-catalyzed intra­molecular silyl­ation of secondary alkyl C–H bonds. (Hydrido)­silyl ethers, generated <i>in situ</i> by de­hydro­gen­ative coupling of a tertiary or conformationally restricted secondary alcohol with diethyl­silane, undergo regio­selective silyl­ation at a secondary C–H bond γ to the hydroxyl group. Oxidation of the resulting oxa­silol­anes in the same vessel generates 1,3-diols. This method provides a strategy to synthesize 1,3-diols through a hydroxyl-directed, functionalization of secondary alkyl C–H bonds. Mechanistic studies suggest that the C–H bond cleavage is the turnover-limiting step of the catalytic cycle. This silyl­ation of secondary C–H bonds is only 40–50 times slower than the analogous silyl­ation of primary C–H bonds

Copper-Catalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes

We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding <i>N</i>-alkyl products. The reactions lead to functionalization at secondary C–H bonds over tertiary C–H bonds and even occur at primary C–H bonds. [(phen)­Cu­(phth)] (<b>1-phth</b>) and [(phen)­Cu­(phth)₂] (<b>1-phth</b>_<b>2</b>), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of <b>1-phth</b> and <b>1-phth</b>_<b>2</b> with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and <i>t</i>BuOO<i>t</i>Bu for the generation of <i>N</i>-alkyl product. Neither <b>1-phth</b> nor <b>1-phth</b>_<b>2</b> reacted with excess cyclohexane at 100 °C without <i>t</i>BuOO<i>t</i>Bu. However, the reactions of <b>1-phth</b> and <b>1-phth</b>_<b>2</b> with <i>t</i>BuOO<i>t</i>Bu afforded <i>N</i>-cyclohexylphthalimide (Cy-phth), <i>N</i>-methylphthalimide, and <i>tert</i>-butoxycyclohexane (Cy-O<i>t</i>Bu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a <i>tert</i>-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr₄, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)­Cu­(phth)₂] with <i>t</i>BuOO<i>t</i>Bu and (Ph­(Me)₂CO)₂ at 100 °C without cyclohexane afforded <i>N</i>-methylphthalimide (Me-phth) from β-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and <i>d</i>₁₂-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C–H cleavage of cyclohexane by a <i>tert</i>-butoxy radical. These mechanistic data imply that the <i>tert</i>-butoxy radical reacts with the C–H bonds of alkanes, and the subsequent alkyl radical combines with <b>1-phth</b>_<b>2</b> to form the corresponding <i>N</i>-alkyl imide product

Copper-Catalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes

We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding <i>N</i>-alkyl products. The reactions lead to functionalization at secondary C–H bonds over tertiary C–H bonds and even occur at primary C–H bonds. [(phen)­Cu­(phth)] (<b>1-phth</b>) and [(phen)­Cu­(phth)₂] (<b>1-phth</b>_<b>2</b>), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of <b>1-phth</b> and <b>1-phth</b>_<b>2</b> with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and <i>t</i>BuOO<i>t</i>Bu for the generation of <i>N</i>-alkyl product. Neither <b>1-phth</b> nor <b>1-phth</b>_<b>2</b> reacted with excess cyclohexane at 100 °C without <i>t</i>BuOO<i>t</i>Bu. However, the reactions of <b>1-phth</b> and <b>1-phth</b>_<b>2</b> with <i>t</i>BuOO<i>t</i>Bu afforded <i>N</i>-cyclohexylphthalimide (Cy-phth), <i>N</i>-methylphthalimide, and <i>tert</i>-butoxycyclohexane (Cy-O<i>t</i>Bu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a <i>tert</i>-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr₄, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)­Cu­(phth)₂] with <i>t</i>BuOO<i>t</i>Bu and (Ph­(Me)₂CO)₂ at 100 °C without cyclohexane afforded <i>N</i>-methylphthalimide (Me-phth) from β-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and <i>d</i>₁₂-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C–H cleavage of cyclohexane by a <i>tert</i>-butoxy radical. These mechanistic data imply that the <i>tert</i>-butoxy radical reacts with the C–H bonds of alkanes, and the subsequent alkyl radical combines with <b>1-phth</b>_<b>2</b> to form the corresponding <i>N</i>-alkyl imide product

Highly Selective C−H Functionalization/Halogenation of Acetanilide

Highly regioselective C−H functionalization/halogenation of acetanilides to produce ortho-haloacetanilides was catalyzed by Pd(OAc)2 and Cu(OAc) 2 with CuX2 as the halogen source

Highly Selective C−H Functionalization/Halogenation of Acetanilide

Highly regioselective C−H functionalization/halogenation of acetanilides to produce ortho-haloacetanilides was catalyzed by Pd(OAc)2 and Cu(OAc) 2 with CuX2 as the halogen source

Highly Selective C−H Functionalization/Halogenation of Acetanilide

Highly regioselective C−H functionalization/halogenation of acetanilides to produce ortho-haloacetanilides was catalyzed by Pd(OAc)2 and Cu(OAc) 2 with CuX2 as the halogen source

Multiple Deprotonations and Deaminations of Phenethylamines to Synthesize Pyrroles

A unique method was discovered to construct polysubstituted pyrroles via an unprecedented multiple deprotonations/deaminations process from commercially available phenethylamines. During this transformation, twelve bonds were broken and five new bonds were constructed