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. 2015 Oct 14;137(40):13066-71.
doi: 10.1021/jacs.5b08019. Epub 2015 Sep 29.

Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls

Tao Liang  1 , Wandi Zhang  1 , Te-Yu Chen  1 , Khoa D Nguyen  1 , Michael J Krische  1
Affiliations

Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls

Tao Liang et al. J Am Chem Soc. .

Abstract

The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo-, and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k, and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k, and 6m, respectively. Primary alcohols 2a, 2l, and 2p were converted to the siloxy-crotylation products 3a, 3l, and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l, and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes.

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Figures

Figure 1
Figure 1
Overview of methods for carbonyl crotylation and the discovery of alkyne mediated crotylation.
Scheme 1
Scheme 1
Dual ruthenium-based catalytic cycles wherein al-kyne-to-allene isomerization occurs in tandem with redox-triggered C-C bond formation.a aArSO3H = 2,4,6-(2-Pr)3PhSO3H.
Scheme 2
Scheme 2
Regio-, diastereo- and enantioselectivity in the redox-triggered C-C coupling of propargyl ether 1a and p-bromobenzyl alcohols 2c.a aArSO3H = 2,4,6-(2-Pr)3PhSO3H. R = p-BrPh. Yield refers to a mixture (Z)-anti-3c and (E)-anti-3c and their enantiomers isolated by silica gel chromatography. See Supporting Information for further experimental details.
Scheme 3
Scheme 3
Deuterium labelling studies exclude allenes as discrete intermediates and are consistent with a hydride shift mechanism.a aYields are of material isolated by silica gel chromatography. See Supporting Information for further details.
Scheme 4
Scheme 4
General catalytic mechanism as corroborated by deuterium labeling experiments.
See this image and copyright information in PMC

References

    1. Selected reviews: O’Hagan D. The Polyketide Metabolites. Ellis Horwood; Chichester: 1991. Rohr J. Angew Chem, Int Ed. 2000;39:2847.Rimando AM, Baerson SR. ACS Symp Ser. 2007;955:1.Itoh T, Dechert-Schmitt AMR, Schmitt DC, Gao X, Krische MJ. Nat Prod Rep. 2014;31:504.

    1. Eribulin mesylate, a truncated derivative of the marine polyether macrolide halichondrin B, is the only commercial polyketide prepared through de novo chemical synthesis: Yu MJ, Zheng W, Seletsky BM. Nat Prod Rep. 2013;30:1158.

    1. Sait M, Hugenholtz P, Janssen PH. Environ Microbiol. 2002;4:654. and references cited therein. - PubMed

    1. For a review on the use of the aldol reaction in polyketide construction, see: Schetter B, Mahrwald R. Angew Chem, Int Ed. 2006;45:7506.

    1. For selected reviews on enantioselective carbonyl allylation and crotylation, see: Yamamoto Y, Asao N. Chem Rev. 1993;93:2207.Ramachandran PV. Aldrichim Acta. 2002;35:23.Kennedy JWJ, Hall DG. Angew Chem, Int Ed. 2003;42:4732.Denmark SE, Fu J. Chem Rev. 2003;103:2763.Yu CM, Youn J, Jung HK. Bull Korean Chem Soc. 2006;27:463.Marek I, Sklute G. Chem Commun. 2007:1683.Hall DG. Synlett. 2007:1644.Li J, Menche D. Synthesis. 2009:2293.Leighton JL. Aldrichim Acta. 2010;43:3.Yus M, González-Gómez JC, Foubelo F. Chem Rev. 2011;111:7774.Ketcham JM, Shin I, Montgomery TP, Krische MJ. Angew Chem, Int Ed. 2014;53:9142.

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