Aerobic alcohol oxidation coupled to palladium-catalyzed alkene hydroarylation with boronic esters
Aerobic alcohol oxidation coupled to palladium-catalyzed alkene hydroarylation with boronic esters
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DOI：
10.1002/anie.200705317
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Sigman, Matthew S.
中科院分区：
文献类型：
--
作者：
Iwai, Yasumasa;Gligorich, Keith M.;Sigman, Matthew S.
The Suzuki reaction, which couples an organohalide and an organoboron compound,[1] is an attractive cross-coupling reaction for use in the synthesis of natural products [2] and pharmaceuticals.[3] This utility is mainly because of the excellent functional group compatibility, ease of preparation of boronic acid derivatives, and the low toxicity of the boron byproducts.[2] The mechanistic details have been widely investigated and the reaction is thought to proceed through oxidative addition of the organohalide (R–X) to Pd0 to form R–PdII–X and then transmetalation of the organoborane (R1–B (OR) 2).[1] The resulting R–PdII–R1 intermediate undergoes reductive elimination to form the product. An exogenous base is required to activate the boronic acid derivative for transmetalation, which is proposed to occur through a four-centered transition state (intermediate C, Scheme 1a).[4]Our group has been developing an alterative route to generate the requisite R–PdII–X intermediate by using an alkene as a synthon for an alkylhalide. To this end, we have recently reported the coupling of an alcohol oxidation to the functionalization of an alkene.[5] Specifically, styrene derivatives and organostannanes undergo a Pd-catalyzed reductive crosscoupling reaction in isopropyl alcohol (IPA) under an aerobic atmosphere to yield hydroarylation product 3a in 76% yield (Scheme 1b). The proposed mechanism proceeds by initial oxidation of the alcoholic solvent to generate PdII-hydride E, which reacts with the alkene to yield Pd-alkyl F (Scheme 1c). Subsequent transmetalation forms G and reductive elimination yields the reductive coupling product and Pd0 (H), which is oxidized by O2 to regenerate the active catalyst (D).[6] As discussed above, boronic acids offer significant practical advantages in cross-coupling reactions with respect to organostannane compounds.[1] However, the development of a reductive coupling of alkenes with boronic acid derivatives was thought to be a significant challenge compared to the use of organostannanes because the strong exogenous base needed to facilitate transmetalation [4] will simultaneously affect the rate of the alcohol oxidation [7](Scheme 1c). The addition of a base can also promote a basemediated reductive elimination of the proposed PdII-hydride intermediate (E) to form Pd0.[8] Herein, we report the development of a catalyst system for the reductive coupling of arylboronic esters and styrenes, and studies that highlight the mechanistic complexity of the reaction.
