Determination of the Absolute Configuration of β-Chiral Primary Alcohols Using the Competing Enantioselective Conversion Method

Burns, Alexander S.; Wagner, A. James; Fulton, Jennifer L.; Young, Kyle; Zakarian, Armen; Rychnovsky, Scott D.

doi:10.1021/acs.orglett.7b01189

Cited by 18 publications

(20 citation statements)

References 31 publications

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“…Initial investigationsu sed isobutyric anhydride 7a as the acyl donor, i-Pr 2 NEt as auxiliary base and chloroform as solvent, as this combination is commonly optimal for the KR of point chiral alcohols. [16][17][18][19] All three catalysts provided good conversion (c = 54-58 %, entries 1-3), however only BTM 6 provided good selectivity (s = 26, entry 3). When using (R)-BTM 6 as catalyst, the recovered BINOL was enriched in the (R)-enantiomer (R)-1,c onsistentw ith the proposed acylation TS models (Scheme 2b).…”

Section: Reactiono Ptimizationmentioning

confidence: 99%

“…Lewis basic isothioureas catalysts, first reported for acyl transfer reactions by Birman and Okamoto, have been applied for the acylative KR of primary, secondary and tertiary alcohols bearing point chirality. The KR of secondary alcohols has been most widely explored, with exceptional selectivities obtained in many cases.…”

Section: Introductionmentioning

confidence: 99%

“…Lewis basic isothioureas catalysts, [15] first reported for acyl transfer reactions by Birman and Okamoto, [16] have been applied for the acylativeK Ro fp rimary, [17] secondary [18] and tertiary [19] alcohols bearingp oint chirality. The KR of secondary alcohols has been mostw idely explored,w ith exceptional selectivitieso btained in many cases.C omputational studies have been used to probe the origin of enantiodiscrimination in these KRs, with acylation transition state structure (TS) models proposed for the fast-and slow-reacting enantiomers (Scheme 2a).…”

Section: Introductionmentioning

confidence: 99%

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Isothiourea‐Catalysed Regioselective Acylative Kinetic Resolution of Axially Chiral Biaryl Diols

Greenhalgh

Smith

2019

Chemistry A European J

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An operationally simple isothiourea‐catalysed acylative kinetic resolution of unprotected 1,1′‐biaryl‐2,2′‐diol derivatives has been developed to allow access to axially chiral compounds in highly enantioenriched form (s values up to 190). Investigation of the reaction scope and limitations provided three key observations: i) the diol motif of the substrate was essential for good conversion and high s values; ii) the use of an α,α‐disubstituted mixed anhydride (2,2‐diphenylacetic pivalic anhydride) was critical to minimize diacylation and give high selectivity; iii) the presence of substituents in the 3,3′‐positions of the diol hindered effective acylation. This final observation was exploited for the highly regioselective acylative kinetic resolution of unsymmetrical biaryl diol substrates bearing a single 3‐substituent. Based on the key observations identified, acylation transition state models have been proposed to explain the atropselectivity of this kinetic resolution.

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Section: Reactiono Ptimizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Isothiourea‐Catalysed Regioselective Acylative Kinetic Resolution of Axially Chiral Biaryl Diols

Greenhalgh

Smith

2019

Chemistry A European J

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“…Lewis basic isothiourea catalysts have been applied for the acylative KR of a wide range of alcohols, including primary alcohols, secondary alcohols, and diols . We recently reported an isothiourea‐catalyzed KR of tertiary heterocyclic alcohols, in which coordinated experimental and computational studies were used to identify the origins of enantiodiscrimination (Figure a).…”

Section: Introductionmentioning

confidence: 99%

Isothiourea‐Catalyzed Acylative Kinetic Resolution of Tertiary α‐Hydroxy Esters

Smith

Laina‐Martín

et al. 2020

Angew Chem Int Ed

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A highly enantioselective isothiourea‐catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently‐developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous‐flow process using a polymer‐supported variant of the catalyst.

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“…Lewis basic isothiourea catalysts [8] have been applied for the acylative KR of aw ide range of alcohols,i ncluding primary alcohols, [9] secondary alcohols, [10] and diols. [11] We recently reported an isothiourea-catalyzedK Ro ft ertiary heterocyclic alcohols, [5h] in which coordinated experimental and computational studies were used to identify the origins of enantiodiscrimination (Figure 2a).…”

Section: Introductionmentioning

confidence: 99%