Chiral Syn-1,3-diol Derivatives via a One-Pot Diastereoselective Carboxylation/ Bromocyclization of Homoallylic Alcohols
Guanxin Huang,
Minjie Liu,
Fangjun Xiong,
Ge Meng,
Yuan Tao,
Yan Wu,
Haihui Peng,
Fener Chen
Affiliations
Guanxin Huang
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China
Minjie Liu
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China
Fangjun Xiong
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China
Ge Meng
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China
Yuan Tao
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China
Yan Wu
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China
Haihui Peng
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China; Corresponding author
Fener Chen
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, P. R. China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Molecules, Shanghai 200433, P. R. China; Corresponding author
Summary: Chiral syn-1,3-diols are fundamental structural motifs in many natural products and drugs. The traditional Narasaka-Prasad diastereoselective reduction from chiral β-hydroxyketones is an important process for the synthesis of these functionalized syn-1,3-diols, but it is of limited applicability for large-scale synthesis because (1) highly diastereoselective control requires extra explosive and flammable Et2BOMe as a chelating agent under cryogenic conditions and (2) only a few functional syn-1,3-diol scaffolds are available. Those involving halogen-functionalized syn-1,3-diols are much less common. There are no reported diastereoselective reactions involving chemical fixation of CO2/bromocyclization of homoallylic alcohols to halogen-containing chiral syn-1,3-diols. Herein, we report an asymmetric synthesis of syn-1,3-diol derivatives via direct diastereoselective carboxylation/bromocyclization with both relative and absolute stereocontrol utilizing chiral homoallylic alcohols and CO2 in one pot with up to 91% yield, > 99% ee, and >19:1 dr. The power of this methodology has been demonstrated by the asymmetric synthesis of statins at the pilot plant scale. : Chemistry; Organic Chemistry; Stereochemistry Subject Areas: Chemistry, Organic Chemistry, Stereochemistry
