Science - USA (2020-08-21)

pyridine moiety of the substrate throughp/p
interactions with one of the naphthalene rings
of the phosphite, coupled with C–H/pand
nonclassical C–H···O hydrogen bonds. This
coordination leads to the differentiation of
enantiotopic C(sp^3 )–Hbonds( 5 , 6 ). Inspired
by this reactivity and the outcome of quan-
tum chemical calculations, we envisaged that

the metal-coordinating pyridine and the metal-

activated C–Hbondsitelinkedintramolecu-

larly within the chiral catalytic pocket might

be replaced with a heterodimer composed of

a pyridine-based receptor ligand with a nonco-

valent interaction donor moiety and a C(sp^3 )–H

borylation substrate with a complementary

functional group (Fig. 1B). Here, we report that

a modular approach for producing a chiral

catalyst ( 22 , 23 ) using a new urea-pyridine

receptor ligand (RL)incombinationwith

the chiral monophosphite-Ir catalyst system

[Ir(Bpin) 3 - L*] led to the discovery of the highly

enantioselective C(sp^3 )–H borylation of ali-

phatic carboxylic amides and esters that oc-

curs specifically at theg-methylene group.

Reyeset al.,Science 369 , 970–974 (2020) 21 August 2020 2of5

Fig. 2. Enantioselectiveg-C–H borylation of 1a catalyzed by an Ir-L-RL
system.Conditions:1a(0.30 mmol), [Ir(OMe)(cod)] 2 (1.5 mol %),L(3.0 mol %),
urea-pyridine ligandRL,U1– 3 (3.3 mol %), pinB–Bpin (1 equiv), 2,6-lutidine
(0.75 equiv), PhMe/CPME 1:1 (2 ml), temperature as stated above. In the cases
whenU1– 3 were used, the reactions were conducted at 25°C, 48 hours, in PhMe/

CPME 1:1 (2 ml). (+) and (–) indicate the presence or absence ofRLor additive

in the catalytic reaction, respectively. *Yields of2aand 4 determined by^1 HNMR.

†Reaction with 6 mol %RL.‡Reaction conducted in the absence ofL*using

6mol%RL. Conditions for the oxidation of2ato3a:NaBO 3 ·4H 2 O(3.0equiv),THF

(tetrahydrofuran)/H 2 O 1:1 (2 ml), room temperature, 3 hours.

RESEARCH | REPORT