1,3,2‐Diazaphospholenes Catalyze the Conjugate Reduction of Substituted Acrylic Acids

Abstract

The potent nucleophilicity and remarkably low basicity of 1,3,2‐diazaphospholenes (DAPs) is exploited in a catalytic, metal‐free 1,4‐reduction of free α,β‐unsaturated carboxylic acids. Notably, the reduction occurs without a prior deprotonation of the carboxylic acid moiety and hence does not consume an additional hydride equivalent. This highlights the excellent nucleophilic character and low basicity of DAP‐hydrides. Functional groups such as Cbz group or alkyl halides which can be problematic with classical transition‐metal catalysts are well tolerated in the DAP‐catalyzed process. Moreover, the transformation is characterized by a low catalyst loading, mild reaction conditions at ambient temperature as well as fast reaction times and high yields. The proof‐of‐principle for a catalytic enantioselective version is described.

Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions

“…Building on our previous work 59 , we envisioned that diazaphospholenes of super hydricity 60 – 62 may provide a good chance to realize HDF of trifluoromethylalkenes via an S N 2’ path 63 . A preliminary attempt indicated that the reaction of α-trifluoromethyl-styrene 2a with diazaphospholene 1 primarily gave the hydrophosphination intermediate A .…”

Mechanistic Insight into the 1,3,2-Diazaphospholene-Catalyzed Reductant (HBpin/NH3BH3)-Controlled Reaction of Allyl 2-Phenylacrylate: Claisen Rearrangement or Hydrogenation?

“…Another plausible pathway is the 1,4-addition pathway. − According to whether the P atom of the 1,3,2-diazaphospholene (DAP) moiety is connected to the C1 or O4 atom, the 1,4-addition can be divided into two types, 1,4-addition (PC) and 1,4-addition (PO) pathways. In the 1,4-addition (PC) pathway, 3 approaches allyl 2-phenylacrylate 4 to form compound 5 PC with an association energy of −2.9 kcal/mol (blue lines in Figure ).…”

Stay positive: catalysis with 1,3,2-diazaphospholenes

“…The potent nucleophilic properties of DAP-hydrides, and their remarkably low basicity, was recently exploited by the Cramer group who showed that the combination of DAP-precatalyst 38 and phenylsilane (PhSiH 3 ) as the terminal reductant can effect the selective 1,4-reduction of α,β-unsaturated carboxylic acids (Scheme 15). 29 Despite the presence of the potentially problematic acidic proton, the reaction smoothly proceeds to completion with only 0.35 equivalents of PhSiH 3 , demonstrating that each hydride on the stoichiometric reducing agent is competent for catalyst turnover, and that any acid-base reactivity is virtually negligible under the reaction conditions and is dominated by the nucleophilic delivery of hydride to the β-position of the substrate. A wide variety of functional groups were well tolerated in the reaction, and when the chiral DAP 29 was employed with pinacol borane as the terminal reductant, 2-phenylpropionic acid was obtained with moderate enantioenrichment (64 : 36 er).…”

“…First generation chiral scaffolds have been based around commercially-available chiral amines, giving quick and efficient access to the targeted DAPs 13-18. 22,23 Subsequent chiral DAPs have employed annulated chiral manifolds to give more rigid DAP structures with conformationally locked stereochemical environments (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). 20,24 The methodologies (both racemic and enantioselective) in which these catalysts and precatalysts have been utilized will now be systematically discussed.…”