Merging the characteristics of transfer hydrogenation and carbonyl addition, we have developed a new class of catalytic enantioselective C–C bond formations. In these processes, hydrogen transfer between alcohols and π-unsaturated reactants generates carbonyl–organometal pairs that combine to deliver products of addition. On the basis of this mechanistic paradigm, lower alcohols are converted directly to higher alcohols in the absence of premetalated reagents or discrete alcohol-to-carbonyl redox reactions. In certain cases, due to a pronounced kinetic preference for primary versus secondary alcohol dehydrogenation, diols and higher polyols are found to engage in catalytic stereo- and site-selective C–C bond formation—a capability that further enhances efficiency by enabling skeletal construction events without extraneous manipulations devoted to the installation and removal of protecting groups. While this Account focuses on redox-neutral couplings of alcohols, corresponding aldehyde reductive couplings mediated by 2-propanol were developed in parallel for most of the catalytic transformations reported herein. Mechanistically, two distinct classes of alcohol C–H functionalizations have emerged, which are distinguished by the mode of pronucleophile activation, specifically, processes wherein alcohol oxidation is balanced by (a) π-bond hydrometalation or (b) C–X bond reductive cleavage. Each pathway offers access to allylmetal or allenylmetal intermediates and, therefrom, enantiomerically enriched homoallylic or homopropargylic alcohol products, respectively. In the broadest terms, carbonyl addition mediated by premetalated reagents has played a central role in synthetic organic chemistry for well over a century, but the requisite organometallic reagents pose issues of safety, require multistep syntheses, and generate stoichiometric quantities of metallic byproducts. The concepts and catalytic processes described in this Account, conceived and developed wholly within the author’s laboratory, signal a departure from the use of stoichiometric organometallic reagents in carbonyl addition. Rather, they reimagine carbonyl addition as a hydrogen autotransfer process or cross-coupling in which alcohol reactants, by virtue of their native reducing ability, drive the generation of transient organometallic nucleophiles and, in doing so, serve dually as carbonyl proelectrophiles. The catalytic allylative and propargylative transformations developed to date display capabilities far beyond their classical counterparts, and their application to the total synthesis of type-I polyketide natural products have evoked a step-change in efficiency. More importantly, the present data suggest that diverse transformations traditionally reliant on premetalated reagents may now be conducted catalytically without stoichiometric metals. This Account provides the reader and potential practitioner with a catalog of enantioselective alcohol-mediated carbonyl additions—a user’s guide, 10-year retrospective, and foundation for future work in this emerging area of catalytic C–C bond formation.

中文翻译：

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通过醇介导的氢转移催化对映选择性羰基烯丙基化和炔丙基化：合并格氏和萨巴蒂尔的化学

结合转移加氢和羰基加成的特征，我们开发了新型的催化对映选择性C–C键形成。在这些过程中，醇与π-不饱和反应物之间的氢转移产生了羰基-有机金属对，这些对结合在一起以提供加成产物。基于这种机理范式，在不存在预金属化试剂或不存在醇与羰基的氧化还原反应的情况下，低级醇直接转化为高级醇。在某些情况下，由于伯醇相对于仲醇脱氢的动力学优先考虑，发现二醇和高级多元醇可参与催化的立体和位点选择性C-C键形成，这种功能可通过进行骨架构建事件而无需专门用于安装和去除保护基的额外操作，从而进一步提高了效率。尽管该文献着重于醇的氧化还原-中性偶联，但对于本文报道的大多数催化转化，并行开发了由2-丙醇介导的相应的醛还原偶联。从机理上讲，出现了两类不同的醇C–H功能化，其特征在于亲核试剂的活化方式，特别是醇氧化通过（a）π键加氢金属化或（b）C–X键还原裂解来平衡的过程。 。每个途径均提供通向烯丙基金属或烯丙基金属中间体的途径，并由此提供对映体富集的均烯丙基或均炔丙基醇产物。从最广泛的意义上讲，由预金属化试剂介导的羰基加成在合成有机化学中已经扮演了重要角色，但是一个世纪以来，必需的有机金属试剂构成了安全问题，需要多步合成，并产生化学计量的金属副产物。该报告中描述的概念和催化过程完全是在作者的实验室内构思和发展的，这标志着羰基加成中化学计量有机金属试剂的使用有所偏离。相反，他们将羰基加成想象为氢自动转移过程或其中醇反应物交叉偶联的过程，凭借其天然的还原能力，驱动瞬态有机金属亲核试剂的生成，并在此过程中兼用作羰基亲电子试剂。迄今为止开发的催化烯丙基化和炔丙基化转化显示能力远远超出其经典对应能力，并且它们在I型聚酮化合物天然产物的全合成中的应用引起了效率的逐步变化。更重要的是，目前的数据表明，传统上依赖于预金属化试剂的各种转化现在可以在没有化学计量金属的情况下催化进行。该帐户为读者和潜在从业人员提供了对映选择性醇介导的羰基加成物的目录-用户指南，十年回顾展，