Atom-efficient processes that occur via addition, redistribution, or removal of hydrogen underlie many large-volume industrial processes and pervade all segments of chemical industry. Although carbonyl addition is one of the oldest and most broadly utilized methods for C–C bond formation, the delivery of nonstabilized carbanions to carbonyl compounds has relied on premetalated reagents or metallic/organometallic reductants, which pose issues of safety and challenges vis-à-vis large-volume implementation. Catalytic carbonyl reductive couplings promoted via hydrogenation, transfer hydrogenation, and hydrogen autotransfer allow abundant unsaturated hydrocarbons to serve as substitutes to organometallic reagents, enabling C–C bond formation in the absence of stoichiometric metals. This Perspective (a) highlights past milestones in catalytic hydrogenation, hydrogen transfer, and hydrogen autotransfer; (b) summarizes current methods for catalytic enantioselective carbonyl reductive couplings; and (c) describes future opportunities based on the patterns of reactivity that animate transformations of this type.

The evolution of methods for carbonyl allylation and crotylation of alcohol proelectrophiles culminating in the design of iodide-bound ruthenium-JOSIPHOS catalysts is prefaced by a brief historical perspective on asymmetric carbonyl allylation and its relevance to polyketide construction. Using gaseous allene or butadiene as precursors to allyl- or crotylruthenium nucleophiles, respectively, new capabilities for carbonyl allylation and crotylation have been unlocked, including stereo- and site-selective methods for the allylation and crotylation of 1,3-diols and related polyols.1 Introduction and Historical Perspective2 Ruthenium-Catalyzed Conversion of Lower Alcohols into Higher Alcohols3 Conclusion and Future Outlook

The first correlation between metal-centered stereogenicity and regioselectivity in a catalytic process is described. Alternate pseudo-diastereomeric chiral-at-ruthenium complexes of the type RuX(CO)[η 3 -prenyl][(S)-SEGPHOS] form in a halidedependent manner and display divergent regioselectivity in catalytic C−C couplings of isoprene to alcohol proelectrophiles via hydrogen autotransfer. Whereas the chloride-bound ruthenium-SEGPHOS complex prefers a trans-relationship between the halide and carbonyl ligands and delivers products of carbonyl secprenylation, the iodide-bound ruthenium-SEGPHOS complex prefers a cis-relationship between the halide and carbonyl ligands and delivers products of carbonyl tert-prenylation. The chlorideand iodide-bound ruthenium-SEGPHOS complexes were characterized in solution and solid phase by 31 P NMR and X-ray diffraction. Density functional theory calculations of the iodide-bound catalyst implicate a Curtin−Hammett-type scenario in which the transition states for aldehyde coordination from an equilibrating mixture of sec-and tert-prenylruthenium complexes are rate-and product-determining. Thus, control of metal-centered diastereoselectivity has unlocked the first catalytically enantioselective isoprene-mediated carbonyl tert-prenylations.