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. 2022 Oct 18;28(58):e202202059.
doi: 10.1002/chem.202202059. Epub 2022 Aug 18.

Asymmetric Organocatalytic Homologation: Access to Diverse Chiral Trifluoromethyl Organoboron Species

Ramasamy Jayarajan  1 , Tautvydas Kireilis  1 , Lars Eriksson  2 , Kálmán J Szabó  1
Affiliations

Asymmetric Organocatalytic Homologation: Access to Diverse Chiral Trifluoromethyl Organoboron Species

Ramasamy Jayarajan et al. Chemistry. .

Abstract

A broad range of aliphatic, aromatic, and heterocyclic boronic acids were successfully homologated using trifluorodiazoethane in the presence of BINOL derivatives to provide the corresponding chiral trifluoromethyl containing boronic acid derivatives in high yields and excellent enantioselectivity. The in situ conversion of the chiral transient boronic acids to the corresponding alcohols or β-CF3 carboxylates are also demonstrated.

Keywords: asymmetric homologation; enantioselective; organoboron; organocatalysis; organofluorine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Bioactive trifluoromethylated and boronic acid derivatives.
Scheme 1
Scheme 1
Methods to access enantioenriched α‐CF3 organoborons
Scheme 2
Scheme 2
Conversion of boronate functionality. [a] Unless otherwise stated: the homologation was done using 1 a (0.1 mmol), 2 (0.3 mmol) and 3 (0.03 mmol, 30 mol %) in 1.0 mL of DCM at r.t. for 72 h [b] d.r. based on 19F NMR. [c] 5 (0.1 mmol) was hydrolyzed with 1.5 M H2SO4 in DME, and then 4 was extracted with toluene under Ar.
Scheme 3
Scheme 3
Scope of asymmetric homologation. [a] Unless otherwise stated the reactions were conducted at room temperature for 72 h using 30 mol % catalyst and 3 h for DanH protection. [b] with 20 mol % catalyst. [c] with 10 mol % catalyst. [d] 1 mmol scale. [e] reaction time 48 h. [f] reactions at 50 °C for 48 h and 2 h for DanH protection. [g] reaction time 54 h.
Scheme 4
Scheme 4
Interconversion of transient chiral boronic acid derivative. [a] the homologation reaction was carried out at 50 °C for 54 h. [b] oxidation was done in THF for 24 h.
Scheme 5
Scheme 5
Catalytic cycle for enantioselective 1,2‐borotropic migration.
See this image and copyright information in PMC

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