Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

Abstract

SummaryRecently, a number of papers have emerged demonstrating copper-catalyzed alkylation reactions of electron-rich small molecules. The processes are generally thought to be related to long established atom-transfer radical reactions. However, unlike classical reactions, these new transformations lead to simple alkylation products. This short review will highlight recent advances in alkylations of nitronate anions, alkenes and alkynes, as well as discuss current mechanistic understanding of these novel reactions.

Cu‐Catalyzed Hydroxymethylation of Unactivated Alkyl Iodides with CO To Provide One‐Carbon‐Extended Alcohols

“…In addition, when the radical‐trapping reagent TEMPO was added to the standard reaction, 2 a was not detected; 28 % of the radical‐trapped product 8 was isolated while 71 % starting material 1 a was recovered (Scheme c). Collectively, these observations are indicative of alkyl radical intermediates during catalysis . Conducting the reaction with styrene under optimized condition resulted in no target alcohol (Scheme d).…”

“…We began our study with 1-iodo-3-phenylpropane (1a)as amodel substrate under 3atm of CO pressure.After screening all the various reaction parameters systematically, a Me IPrCuCl catalyst with the addition of 3.0 equiv of diethoxymethylsilane and 2.0 equiv of LiOMe was found to be critical to achieve good yield of the desired alcohol product ( Table 1, entry 1; see the Supporting Information for more details). Conducting the reaction at 60 8 8Ca nd at 3atm of CO pressure also were found to be required (entries [14][15]. Although other NHC ligands such as IPr, SIPr, Cl IPr, and IMes can be used in this transformation, they only provided moderate yields (entries 3-6).…”

“…[15] Conducting the reaction with styrene under optimized condition resulted in no target alcohol (Scheme 2d). The desired alcohol 2a was observed in 97 %y ield, which shows that the acyl iodide can serve as an intermediate in the catalytic transformation.…”

Cu‐Catalyzed Hydroxymethylation of Unactivated Alkyl Iodides with CO To Provide One‐Carbon‐Extended Alcohols

“…Collectively,t hese observations are indicative of alkyl radical intermediates during catalysis. [15] Conducting the reaction with styrene under optimized condition resulted in no target alcohol (Scheme 2d). This observation allows us to exclude apossible pathway involving base-mediated HI elimination followed by hydrocupration/ formylation.…”

“…Decreasing the amount of catalyst to 5mol %d iminished the yield measurably (entry 13). Conducting the reaction at 60 8 8Ca nd at 3atm of CO pressure also were found to be required (entries [14][15].…”