Catalytic enantioselective ethylalumination of terminal alkenes: substrate effects and absolute configuration assignment

The chemo- and enantioselectivity of the reaction of alkenes with AlEt3 catalyzed by bis(1-neomenthylindenyl)zirconium dichloride has been studied. The reaction with linear alkenes in a chlorinated solvent (CH2Cl2) gives mainly carbometallation products in 70–80% yield and with enantiomeric purity of 47–70%ee with an (S)-configuration. In the case of vinylcycloalkanes and styrene, the reaction provides roughly equal amounts of carbometallation products and substituted alumolanes with enantioselectivities of 39–69%ee and 40–57%ee, respectively.(R)-MTPA and (R)-2-phenylselenopropionic acid [(R)-PSPA] were used as the derivatization reagents for enantiomeric excess estimation and the absolute configuration assignment of β-chiral primary alcohols and 2-substituted 1,4-butanediols resulting from oxidation and hydrolysis of the organoaluminum products. It was shown that the specific rotation changes sign in the series of enantiomerically enriched 2-ethyl-1-alkanols when going from β-ethyl-substituted octanol to nonanol. The conformational analysis of the MTPA and PSPA esters of 2-ethyl-1-alkanols was performed and a dependence of their conformational composition on the type of substituent at the β-stereogenic center was established. Calculation of the 77Se NMR chemical shifts of the possible conformers of the PSPA esters demonstrated that the conformation of the selenium moiety has the most pronounced effect on the δSe value. The high efficiency of PSPA application for the enantiomeric purity estimation and the absolute configuration assignment of 2-ethyl-1-alkanols is shown.

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(2S)-Ethyl-1-heptanolC9H20OEe = 60%[α]D25 = +1.7 (c 1.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Ethyl-1-oсtanolC10H22OEe = 47%[α]D25 = +1.2 (c 4.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Ethyl-1-nonanolC11H24OEe = 70%[α]D25 = −1.5 (c 4.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Ethyl-1-decanolC12H26OEe = 69%[α]D25 = −1.3 (c 4.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Ethyl-4-methyl-1-pentanolC8H18OEe = 60%[α]D25 = +2.7 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Cyclohexyl-1-butanolC10H20OEe = 62%[α]D25 = +4.5 (c 0.4, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Cyclooctyl-1-butanolC12H24OEe = 39%[α]D25 = +2.5 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Phenyl-1-butanolC10H14OEe = 69%[α]D25 = −8.7 (c 0.4, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Benzyl-1-butanolC11H16OEe = 52%[α]D25 = +1.1 (c 0.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Cyclohexyl-1,4-butanediolC10H20O2Ee = 57%[α]D25 = −5.3 (c 1.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-Cyclooctyl-1,4-butanediolC12H24O2Ee = 45%[α]D25 = −7.5 (c 1.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2R)-Phenyl-1,4-butanediolC10H14O2Ee = 40%[α]D25 = −11.7 (c 1.2, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)