amounts of free amine 1 under the standard
conditions afforded no observed product,
whereas substoichiometric amounts of 1 (0.1
equivalents) with 1 ·BF 3 (0.9 equivalents) afforded
product 3 in comparable yields (entries 6 and
7). In all cases examined for allylic C–H ami-
nation cross-coupling (AACC) (vide infra), use
of 1 equivalent of each cross-coupling partner
under conditions open to air and moisture
furnished preparative yields of tertiary allylicamine products as pure regio- (>20:1 linear:
branched) and stereoisomers (>20:1E:Z).
These results contrast with allylic amina-
tions proceeding through tandem olefin
functionalization-elimination pathways, whichSCIENCEscience.org 15 APRIL 2022•VOL 376 ISSUE 6590 279
Fig. 3. Synthesis of complex tertiary aliphatic amine drugs and drug derivatives.(AandB) All reactions were run under ambient conditions. Unless otherwise indicated,
all reactions were run on a 0.2-mmol scale using amine-BF 3 (1 equivalent), olefin (1 equivalent), Pd(OAc) 2 (10 mol %), (±)-MeO-SOX (10 mol %), 2,5-DMBQ (1.1 equivalents), and
dbp in solvent (1 M) at 45°C for 48 hours, followed by basic workup. All amination products were formed in >20:1 L:B and >20:1E:Zselectivity, and isolated yields of the
free tertiary amine products are the average of three experiments. *25% dbp in dioxane.†50% dbp in dioxane.‡25% dbp in toluene. §50% dbp in toluene. ¶50% dbp in methyl
tert-butyl ether. #50% dbp in benzene. **5% dbp in dioxane.††5 mol % (±)-MeO-SOX·Pd(OAc) 2 .‡‡24 hours. §§72 hours. ¶¶Average of two experiments.
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