One-Pot Alkene Hydroboration/Palladium-Catalyzed Migratory Suzuki–Miyaura Cross-Coupling

Abstract

Chain-walking is a powerful approach toward the functionalization of C−H bonds remote to a functional group. Whereas various Pdcatalyzed migratory cross-couplings have been developed in the past years, the design of an efficient migratory version of the popular Suzuki−Miyaura cross-coupling has remained elusive. The current article reports a one-pot procedure consisting of alkene hydroboration and migratory Suzuki−Miyaura coupling of the resulting alkylboronic acid intermediate. A high regioselectivity for the benzylic position of the initial alkene was achieved by using P(t-Bu) 2 Me as the ligand and an ortho-substituted aryl electrophile. Regioconvergence from alkene positional and geometrical isomers and long-range migration were demonstrated. Mechanistic investigations indicated that the migration occurs through a partially reversible, nondissociative mechanism.

Cobalt-Catalyzed Remote Hydroboration of Alkenyl Amines

“…Unsurprisingly, the reaction of Z - 1a proceeded efficiently to afford aminoalcohol 2a in 74% yield (eq 2), suggesting the configuration of alkenes did not interfere with the chain walking process. Moreover, a deuterated reaction was carried out with allylic amine 1b and DBpin, and the deuterium was found to be incorporated along the alkyl chain (eq 3), which is consistent with the chain walking mechanism (β-hydride elimination and reinsertion). , The deuterium incorporation at the α-position of D - 2b indicated that an enamine might be an intermediate in the isomerization via the β-hydride elimination. Consequently, enamine 1ah was prepared and treated with the standard reaction conditions.…”

Air‐Stable PdI Dimer Enabled Remote Functionalization: Access to Fluorinated 1,1‐Diaryl Alkanes with Unprecedented Speed

“…Aside from the product selectivity, the overall reaction speed of only 10 min at room temperature is unprecedented also (as compared to 24 h reaction times in Ni‐based couplings or 48 h in Pd‐based protocols) [4–6] . Since the chain walking relies on the analogous elementary steps as other Pd‐based protocols (i.e.…”

Air‐Stable PdI Dimer Enabled Remote Functionalization: Access to Fluorinated 1,1‐Diaryl Alkanes with Unprecedented Speed

“…[5] In this context Baudoin recently reported a notable advance which relied on Pd-catalysis and could tolerate ortho-substituents, albeit requiring high temperatures (120 8C) during 48 hours and a terminal blocking group in the substrate to prevent alternative products (see Figure 1 B). [6,7] Ortho-fluorinated 1,1-diaryl alkane motifs were not showcased. These motifs are of distinct importance, being featured in numerous bioactive compounds [8] with anti-HIV, anti-fungal or anti-blood clotting activities, for example.…”

“…Electronic variations of the aryl group of the coupling partner are well tolerated, ranging from electron donating tert-butyl (9) to electron withdrawing trifluoromethyl-substituted aryl moieties (4,10). Notably, the ortho-methyl and -isopropyl groups (6,7) did not affect the reaction speed and efficiency, and only minimally effected the product selectivity (branched vs. linear). While as large substituents as isopropyl have so far not been showcased, the smaller ortho-methyl substituent (as in 6) could otherwise only be tolerated under much harsher conditions, such as Baudoins recent protocol, [6] requiring 120 8C and 48 h reaction time or Zhus protocol, [5c] needing 80 8C for 24 h. Potentially coordinating functionalities such as the cyano group ( 13) did not impede the reaction.…”

“…Aside from the product selectivity, the overall reaction speed of only 10 min at room temperature is unprecedented also (as compared to 24 h reaction times in Ni-based couplings or 48 h in Pd-based protocols). [4][5][6] Since the chain walking relies on the analogous elementary steps as other Pdbased protocols (i.e. Pd II b-H elimination and reinsertion, see Bu)] 2 (0.005 mmol, 2.5 mol %), organozinc reagent (0.24 mmol, 1.2 equiv, in THF) in NMP (1.5 mL) for 10 min at r.t. under argon.…”