Preparation and reactions of enantiomerically pure α-functionalized grignard reagents

TY - JOUR

T1 - Preparation and reactions of enantiomerically pure α-functionalized grignard reagents

AU - Rayner, P.J.

AU - O'Brien, P.

AU - Horan, R.A.J.

PY - 2013/5/29

Y1 - 2013/5/29

N2 - A strategy for the generation of enantiomerically pure α- functionalized chiral Grignard reagents is presented. The approach involves the synthesis of α-alkoxy and α-amino sulfoxides in ≥99:1 dr and ≥99:1 er via asymmetric deprotonation (s-BuLi/chiral diamine) and trapping with Andersen's sulfinate (menthol derived). Subsequent sulfoxide → Mg exchange (room temperature, 1 min) and electrophilic trapping delivers a range of enantiomerically pure α-alkoxy and α-amino substituted products. Using this approach, either enantiomer of products can be accessed in 99:1 er from asymmetric deprotonation protocols without the use of (-)-sparteine as the chiral ligand. Two additional discoveries are noteworthy: (i) for the deprotonation and trapping with Andersen's sulfinate, there is a lack of stereospecificity at sulfur due to attack of a lithiated intermediate onto the α-alkoxy and α-amino sulfoxides as they form, and (ii) the α-alkoxy-substituted Grignard reagent is configurationally stable at room temperature for 30 min.

AB - A strategy for the generation of enantiomerically pure α- functionalized chiral Grignard reagents is presented. The approach involves the synthesis of α-alkoxy and α-amino sulfoxides in ≥99:1 dr and ≥99:1 er via asymmetric deprotonation (s-BuLi/chiral diamine) and trapping with Andersen's sulfinate (menthol derived). Subsequent sulfoxide → Mg exchange (room temperature, 1 min) and electrophilic trapping delivers a range of enantiomerically pure α-alkoxy and α-amino substituted products. Using this approach, either enantiomer of products can be accessed in 99:1 er from asymmetric deprotonation protocols without the use of (-)-sparteine as the chiral ligand. Two additional discoveries are noteworthy: (i) for the deprotonation and trapping with Andersen's sulfinate, there is a lack of stereospecificity at sulfur due to attack of a lithiated intermediate onto the α-alkoxy and α-amino sulfoxides as they form, and (ii) the α-alkoxy-substituted Grignard reagent is configurationally stable at room temperature for 30 min.

UR - http://www.scopus.com/inward/record.url?scp=84878389857&partnerID=8YFLogxK

U2 - 10.1021/ja4033956

DO - 10.1021/ja4033956

M3 - Article

AN - SCOPUS:84878389857

SN - 0002-7863

VL - 135

SP - 8071

EP - 8077

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 21

ER -