Science - USA (2022-04-29)

To gauge improvements in the functional
group tolerance, compound X2 and cyclo-
hexanoic acid were resubjected to the earlier
additive screen in the presence of phthalimide,
and overall reaction performance was subs-
tantially better (Fig. 2C, right, and fig. S13). A

range of compounds that previously served as

reaction poisons (e.g., 1,3-dicarbonyls and

benzoic acids) were now well tolerated. Fur-

thermore, examining the data in aggregate

showed that the overall average yield nearly

doubled in the presence of phthalimide, and

the overall number of reaction poisons (de-

fined as decreasing the yield by >33%) fell

from 390 to 208.

With these exciting results in hand, we

sought to benchmark the reaction improve-

ment in a pharmaceutically relevant context

SCIENCEscience.org 29 APRIL 2022¥VOL 376 ISSUE 6592 535

Fig. 3. Scope of the decarboxylative arylation.(A) Scope of the Aryl Halide Informer Library investigated against tetrahydropyran-4-carboxylic acid (% CAD yield
reported). (B) Nanoscale high-throughput scope evaluation (% isolable reported). A product is deemed isolable if the CAD yield is≥10%.n, number of evaluated
compounds in this category; EDG, electron-donating group.

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