Science - USA (2020-03-13)

of the quaternizingN-benzyl group. Encourag-
ingly,L·1c(4-CF 3 C 6 H 4 ) gave increased enantio-
selectivity (39% ee) andL·1d(3,4,5-F 3 C 6 H 2 )
resulted in a further improvement (52% ee).
Focusing attention on the meta positions of
the outer arenes of the teraryl system, we then
evaluated a series of substituents (L·1eto
L·1i). Trifluoromethyl (L·1e) and methoxy
(L·1f) substitution again gave increases (both
60% ee), but the biggest gain came from the
tert-butyl substitutedL·1g(73% ee). At this

point, we investigated aryl groups in these

positions to extend the reach even further, but

both of these proved detrimental (L·1hand

L·1i). Thus, we shifted our attention to other

reaction parameters withL·1g. A solvent eval-

uation identified cyclopentyl methyl ether

(CPME) as being optimal, in that the reaction

temperature could be reduced to−10°C while

high reactivity was maintained, resulting in iso-

lation of3ain 72% yield and with 96% ee, fol-

lowing oxidation to the corresponding phenol

with H 2 O 2 (see inset in Fig. 2A). This deriva-

tization aided separation from any remain-

ing starting material or difunctionalized material.

The undesired borylation of monoborylated3a′

to give a symmetrical diborylated by-product did

occur to varying degrees in the reactions, being

unavoidable at higher conversions. We thus

carried out careful experiments to establish

whether kinetic resolution may be occurring

in such instances, resulting in possible en-

hancement of the observed ee of3a′at the

Genovet al.,Science 367 , 1246–1251 (2020) 13 March 2020 2of6

Fig. 1. Strategy for

incorporating chiral

cations with transition

metals.(A) Applications

of chiral cations in

asymmetric catalysis.

Me, methyl; Ph, phenyl;

R, substituent. (B) General

strategy for integration of

transition metal (TM)

catalysis with chiral

cations. M, metal.

(C) State-of-the-art

methodology for enantiose-

lective remote C–H

activation of arenes.

Boc, butyloxycarbonyl;

Ac, acetyl; BNDHP,

1,1′-binaphthyl-2,2′-diyl

hydrogenphosphate.

(D) Our prior work

controlling regioselectivity

in arene borylation.

Bu, butyl. (E) Summary

of this work.

RESEARCH | REPORT