Page 85 - Science

RESEARCH | REPORT

Fig. 2. Initial reac-
tion development.
(A) Stoichiometric
studies: Viability
of cyclometallated
Cp*Ir(III) complex as
aC–H insertion cata-
lyst. (B)DFT-calculated
competitive working
modes from Ir(V)-
acylimido species VI.
(C) Principle of the
catalyst design.
(D) Catalyst optimiza-
tion study. Unless
otherwise indicated,
reactions were run
with 10 mol % of
F
catalyst and NaBAr 4
in dichloromethane-d 2
at room temperature
for 12 hours; the
product yields were
1
measured with H
NMR spectroscopy. Downloaded from
Yields for side product
6 are indicated in
parentheses. *Run
at 40°C. †Run for
6 hours. ‡Run for
F
2 hours. Ar ,3,5-
bis(trifluoromethyl)
phenyl; rt, room http://science.sciencemag.org/
temperature; Ts, p-
toluenesulfonyl; Meoc,
methyloxycarbonyl.

on March 1, 2018

the deleterious inhibitory effect caused by C–H amidation by exploring a wide range of sub- catalystXIVprovidedthecorrespondingg-lactams
strong coordination of the product to the cat- strates (Fig. 3). Various 1,4,2-dioxazol-5-ones were in high yields (5, 7–10), even in the presence of a
alyst (11, 13), such that post-modification was accessed from abundant carboxylic acid feedstock Boc-protected free N–H group (11). The forma-
necessary for catalytic turnover. Our method- by two-step sequences consisting of acid activation/ tion of 2,2-dimethyl lactam 12,however,required
ology enables the direct preparation of unpro- hydroxamic acid formation followed by carbon- slightly higher temperature (80°C), presumably
tected g-lactam products without any additional ylative cyclization; both of these steps are highly as a result of the steric crowding adjacent to the
transformation. efficient, and the dioxazolones can be easily dioxazolone moiety. Functionalization of a sec-
Having identified the optimal catalysts, we in- prepared in excellent yields. The cyclization of ondary benzylic C–H bond in the cyclopentyl ring
vestigated the generality of the iridium-catalyzed substrates containing benzylic C–H bonds with resulted in cis-tricyclic g-lactam (13)asasole

Hong et al., Science 359, 1016–1021 (2018) 2 March 2018 3of 6