Letter Cite This: Org. Lett. 2018, 20, 5375−5379
pubs.acs.org/OrgLett
Borinic Acid-Catalyzed, Regioselective Ring Opening of 3,4-Epoxy Alcohols Grace Wang, Graham E. Garrett, and Mark S. Taylor* Department of Chemistry, University of Toronto, 80 St. George St., Toronto, Ontario M5S 3H6, Canada
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S Supporting Information *
ABSTRACT: Diarylborinic acids (Ar2BOH) catalyze the C3selective ring opening of 3,4-epoxy alcohols with aniline, dialkylamine and arenethiol nucleophiles. The regiochemical outcome is consistent with a catalytic tethering mechanism in which the borinic acid interacts with both the electrophile and the nucleophile. The rate acceleration resulting from this induced intramolecularity effect is sufficient to overcome steric biases that would otherwise favor C4-selective opening of the substituted epoxy alcohols.
R
Scheme 1. Proposed Mechanism for Borinic Acid-Catalyzed Chloroacylation of 2,3-Epoxy Alcohols, and Extension to 3,4-Epoxy Alcohol Substrates
ing-opening reactions of epoxides are a useful class of methods for carbon−heteroatom and carbon−carbon bond formation.1 Challenges related to control of stereoselectivity and regioselectivity have prompted the development of new protocols and catalysts for such transformations.2,3 With regard to the latter issue, the introduction of a functional group capable of interacting with a Lewis acidic reagent or catalyst has enabled regioselective ring openings of substrates lacking a strong electronic or steric bias. 2,3-Epoxy alcohols and their derivatives have been especially useful for such transformations.3−8 One-carbon homologation to the 3,4epoxy alcohol congeners changes the situation significantly: few methods for regioselective ring opening of such substrates have been reported. Nickel-catalyzed aminolysis and arylation reactions developed by Yamamoto and co-workers,9,10 and a europium(III) trifluoromethanesulfonate-catalyzed methanolysis reported by the Iwabuchi group,11 are important examples of C4-selective processes. Here, we report a method for C3selective ring-opening of 3,4-epoxy alcohols using an electrondeficient diarylborinic acid (Ar2BOH) as catalyst. Aniline derivatives are particularly efficient nucleophiles in this process, but reactions of arenethiols and dialkylamines are also demonstrated. The C3-selectivity, which apparently results from induced intramolecularity via a catalytic tethering mechanism,12−16 is sufficiently robust as to overcome steric bias in substrates that would otherwise favor attack at the 4position. Our group has developed borinic-acid-catalyzed siteselective chloroacylation and chlorosulfonylation reactions of 2,3-epoxy alcohols.17 Kinetics experiments and computational modeling suggested that the organoboron catalyst influenced the site selectivity of both the ring-opening and Ofunctionalization steps through the formation of a borinic ester intermediate (see Scheme 1).18 While exploring the scope of this process, we applied the chloroacylation protocol to a single 3,4-epoxy alcohol substrate (compound 2a), and obtained product 3.17 The C3-selective ring-opening was inconsistent with chelation by the borinic acid catalyst, but © 2018 American Chemical Society
instead suggested internal delivery of chloride via an adduct such as A. This unexpected observation prompted us to explore borinic acids as catalysts for the ring openings of 3,4epoxy alcohols. Other relevant precedents include the studies by Miyashita and co-workers regarding the organoboronpromoted ring openings of 2,3-epoxy alcohols,7 as well as several reported organoboron-catalyzed or organoboronpromoted transformations of alcohol-bearing substrates that have been proposed to operate through tethering mechanisms.19−23 A survey of catalysts (see the Supporting Information (SI)) revealed that bis(para-fluorophenyl)borinic acid (1b)24 Received: July 21, 2018 Published: August 27, 2018 5375
DOI: 10.1021/acs.orglett.8b02295 Org. Lett. 2018, 20, 5375−5379
Letter
Organic Letters
Scheme 2. Borinic Acid-Catalyzed, C3-Selective Ring Openings of 2b with Aniline, Dialkylamine and Arenethiol Nucleophilesa
a
Yields (0.2−1.0 mmol scale) after purification by silica gel chromatography.
Scheme 3. Variation of the 3,4-Epoxy Alcohol Electrophilea
a
Yield of the mixture of regioisomers (0.2 mmol scale) after purification by silica gel chromatography. Compounds 5b′ and 5c were each isolated as a mixture with a substituted tetrahydrofuran side product.
acylation or sulfonylation was needed for catalyst turnover in the reactions of 2,3-epoxy alcohols,18 this was not the case for the aminolysis of 2b: turnover was presumably achieved by simple protonolysis of the B−O bond. On 1 mmol scale with 4 mol % of catalyst 1b, product 4a was isolated in 99% yield. The scope of nucleophiles capable of participating in the borinic acid-catalyzed, C3-selective ring-opening process proved to be quite broad (see Scheme 2). A variety of
displayed particularly high activity for the addition of aniline to trans-disubstituted 3,4-epoxy alcohol (2b) (product 4a; see Scheme 2). Consistent with the result obtained upon chloroacylation of 2a and the proposed catalytic tethering mechanism, the ring opening was C3-selective (>19:1, as judged by analysis of the unpurified reaction mixture by 1H NMR spectroscopy). Whereas functionalization of the relatively stable five-membered borinic ester adduct by 5376
DOI: 10.1021/acs.orglett.8b02295 Org. Lett. 2018, 20, 5375−5379
Letter
Organic Letters substituted anilines, as well as N-alkylated derivatives, were tolerated (products 4a−4j). Dialkylamines reacted at lower rates, but synthetically useful yields of products 4k and 4l were obtained at higher catalyst loadings. The process was also applicable to arenethiols (products 4m−4o). Whereas the aminolysis reactions were conducted without attempts to exclude air or moisture, the use of an inert argon atmosphere provided an improvement in yields for reactions of thiol nucleophiles. Ring openings of 2b with alkylthiols were less efficient, resulting in 36% and 30% yields of the C3-substituted products from 1-hexanethiol and benzyl mercaptan, respectively (see the SI). Limitations were also encountered using phenol (
