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. 2025 Aug 6;147(31):28370-28377.
doi: 10.1021/jacs.5c09358. Epub 2025 Jul 28.

anti-Diastereo- and Enantioselective Ruthenium-Catalyzed C-C Coupling-Oxidative Lactonization of 1,4-Butanediol: Alkynes as Allylmetal Pronucleophiles

Catherine G Santana  1 , Peyton W Meares  1 , Zachary J Dubey  1 , Michael J Krische  1
Affiliations

anti-Diastereo- and Enantioselective Ruthenium-Catalyzed C-C Coupling-Oxidative Lactonization of 1,4-Butanediol: Alkynes as Allylmetal Pronucleophiles

Catherine G Santana et al. J Am Chem Soc. .

Abstract

Reported methods for enantioselective oxidative lactonization affect desymmetrization of prochiral or meso-diols, and processes where C-C bond formation accompanies oxidative lactonization are undescribed. Here, using the ruthenium catalyst assembled from RuHCl(CO)(PPh3)3, JOSIPHOS SL-J009-1 and KI, allylative oxidative lactonizations of 1,4-butanediol (106 tons/yr) are described that occur with high levels of anti-diastereo- and enantioselectivity. As corroborated by deuterium labeling experiments, these processes merge three distinct catalytic events: (a) alkyne-to-allene isomerization, (b) transfer hydrogenative carbonyl (α-aryl)allylation of the allene pronucleophile, and (c) oxidative lactonization of the resulting enantiomerically enriched 1°,2°-diol.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Catalytic oxidative lactonization.
Figure 2.
Figure 2.
Thorpe-Ingold effects promote mono-allylation.
Figure 3.
Figure 3.
Reactions of diols 2b, 2c and deuterium labelling experiments.a aYields are of material isolated by silica gel chromatography. Deuterated compounds were characterized by 1H NMR, 2H NMR and HRMS. See Supporting Information for further experimental details.
Figure 4.
Figure 4.
Corroborating intervention of lactol dehydro-2a and mono-allylated diol 2d.a aYields are of material isolated by silica gel chromatography. See Supporting Information for further experimental details.
Scheme 1.
Scheme 1.
Proposed catalytic cycle for enantioselective ruthenium-catalyzed (α-aryl)allylation-oxidative lactonization.
See this image and copyright information in PMC

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