Carbonyl Allylation and Crotylation: Historical Perspective, Relevance to Polyketide Synthesis, and Evolution of Enantioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer Processes

Abstract

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

Chiral-at-Ruthenium-SEGPHOS Catalysts Display Diastereomer-Dependent Regioselectivity: Enantioselective Isoprene-Mediated Carbonyl tert-Prenylation via Halide Counterion Effects

“…Not only was a halide-dependent partitioning of diastereomeric chiral-at-ruthenium-SEGPHOS complexes observed, but it was also found that the diastereomeric complexes display regiodivergent reactivity: chloride- and bromide-bound ruthenium-SEGPHOS catalysts preferentially promote carbonyl sec -prenylation, whereas the pseudo -diastereomeric iodide-bound ruthenium-SEGPHOS catalyst delivers products of carbonyl tert -prenylation. These data represent the first correlation between metal-centered stereogenicity and regio­selectivity in metal catalysis, which, in turn, has enabled a method for catalytic enantio­selective isoprene-mediated carbonyl tert -prenylation beyond premetalated reagents. – …”

β-Hydroxy Esters as Malonic Semialdehyde Proelectrophiles in Enantioselective Butadiene-Mediated Crotylation: Total Synthesis of Octalactins A and B

“…Yields of material isolated by silica gel chromatography are reported. Diastereoselectivities and linear:branched regioselectivities were determined by 1 H NMR analysis of crude reaction mixtures. See the Supporting Information for further details.…”

Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C–C Couplings via Hydrogen Transfer

“…Guided and inspired by this characteristic, our laboratory has developed diverse byproduct-free catalytic carbonyl additions that occur through the reductive activation of π-unsaturated pronucleophiles under the conditions of hydrogenation or hydrogen auto-transfer from alcohol proelectrophiles (Figure ). These processes represent an alternative to carbonyl additions mediated by stoichiometric organometallic reagents, which are often hazardous, functional-group-intolerant, and generate metal-containing waste. Hydrogen auto-transfer for carbonyl addition is mechanistically distinct from related “borrowing hydrogen” reactions that promote hydroxyl substitution of alcohol reactants …”

“…To date, nearly all asymmetric reactions of this type have been catalyzed by iridium­(III) and ruthenium­(II) complexes . Such octahedral d 6 metal ions possess unoccupied d z 2 and d x 2 – y 2 orbitals.…”