Catalytic Direct Dehydrogenative Cross-Couplings of C–H (Pro)Nucleophiles and Allylic Alcohols without an Additional Oxidant

Transition-metal-catalyzed cross-coupling
reactions between sp2-hybridized C atoms are of prime importance
in both target
and diversity oriented synthesis. Ideal cross-coupling reactions would
neither require any leaving groups nor stoichiometric reagents. In
this article, we report the first direct dehydrogenative cross-couplings
between aromatic C–H bonds (in most cases using indole substrates)
and allylic alcohols, which do not require an additional classical
stoichiometric oxidizing agent and provide β-arylketones as
value-added products. Ruthenocene- or ferrocene-based bismetallacycles,
in which either Pd­(II) or Pt­(II) are the catalytically active centers,
were found to be particularly efficient catalysts. Control experiments
suggest that the bismetallacycles initially transform the allylic
alcohols into vinylketones, which then alkylate the aromatic substrate
in the presence of the catalyst. The fact that the dehydrogenative
coupling does not require a classical stoichiometric oxidizing agent
is explained either by protonolysis of a metallacyclic M­(II)-H intermediate
or by a mechanism in which an excess of the allylic alcohol substrate
serves as a sacrificial hydrogen acceptor. The title reaction is supported
by cocatalytic amounts of Ni­(OAc)2. In preliminary studies,
it was observed that the title reaction can as well be applied to
prochiral CH-acidic pronucleophiles such as α-cyanoacetates,
representing the first examples for direct enantioselective β-ketoalkylations
via allylic alcohols in the absence of an additional oxidant.

过渡金属催化sp²杂化碳原子间的交叉偶联反应（Transition-metal-catalyzed cross-coupling reactions between sp²-hybridized C atoms）在靶向合成与多样性导向合成中均具有核心地位。理想的交叉偶联反应既无需离去基团，也无需化学计量试剂。
本文首次报道了芳香族C-H键（多数以吲哚底物（indole substrates）为反应底物）与烯丙醇之间的直接脱氢交叉偶联反应，该反应无需额外使用经典化学计量氧化剂，可生成β-芳基酮（β-arylketones）作为高附加值产物。
研究发现，以钌茂或二茂铁基双金属环（Ruthenocene- or ferrocene-based bismetallacycles）为催化剂时表现出尤为优异的催化活性，这类催化剂的催化活性中心为Pd(II)或Pt(II)。
对照实验显示，双金属环首先将烯丙醇转化为乙烯基酮（vinylketones），随后在催化剂存在下对芳香底物进行烷基化修饰。
该脱氢偶联反应无需经典化学计量氧化剂的原因可通过两种路径解释：一是金属环型M(II)-氢中间体（metallacyclic M(II)-H intermediate）的质子解过程，二是过量的烯丙醇底物充当牺牲性氢受体的反应机制。
本标题反应可通过催化量的乙酸镍(II)（Ni(OAc)2）实现辅助催化。
在初步研究中，我们发现该反应同样可应用于前手性CH酸性亲核前体（prochiral CH-acidic pronucleophiles）如α-氰乙酸酯（α-cyanoacetates），这代表了无需额外氧化剂、以烯丙醇为原料的对映选择性β-酮烷基化（enantioselective β-ketoalkylations）反应的首例实例。