Benzylic Primary Amines Research Articles

Harnessing Sulfur(VI) Fluoride Exchange Click Chemistry and Photocatalysis for Deaminative Benzylic Arylation.

While among the most common functional handles present in organic molecules, amines are a widely underutilized linchpin for C-C bond formation. To facilitate C-N bond cleavage, large activating groups are typically used but result in the generation of stoichiometric amounts of organic waste. Herein, we report an atom-economic activation of benzylic primary amines relying on the Sulfur(VI) Fluoride Exchange (SuFEx) click chemistry and the aza-Ramberg-Bäcklund reaction. This two-step sequence allows the high-yielding generation of 1,2-dialkyldiazenes from primary amines via loss of SO2. Excitation of the diazenes with blue light and an Ir photocatalyst affords radical pairs upon expulsion of N2, which can be coaxed into the formation of C(sp3)-C(sp2) bonds upon diffusion and capture by a Ni catalyst. This arylative strategy relying on a traceless click approach was harnessed in a variety of examples and its mechanism was investigated.

Formal α-Allylation of Primary Amines by a Dearomative, Palladium-Catalyzed Umpolung Allylation of N-(Aryloxy)imines.

N-(Aryloxy)imines, readily accessible by condensation/tautomerization of (pseudo)benzylic primary amines and 2,6-di-tert-butyl-1,4-benzoquinone, undergo efficient allylation to afford a wide range of homoallylic primary amines following hydrolytic workup. Deprotonation of N-(aryloxy)imines generates a delocalized 2-azaallyl anion-type nucleophile that engages in dearomative C-C bond-forming reactions with allylpalladium(II) electrophiles generated from allylic tert-butyl carbonates. This reactivity umpolung enables the formal α-allylation of (pseudo)benzylic primary amines. Mechanistic studies reveal that the apparent regioselectivity of the desired bond-forming event is a convergent process that is initiated by unselective allylation of N-(aryloxy)imines to give several regioisomeric species, which subsequently rearrange via stepwise [1,3]- or concerted [3,3]-sigmatropic shifts, ultimately converging to provide the desired regioisomer of the amine products.

Transforming Benzylic Amines into Diarylmethanes: Cross-Couplings of Benzylic Pyridinium Salts via C-N Bond Activation.

A nickel-catalyzed cross-coupling of benzylic pyridinium salts with arylboronic acids was developed. Coupled with chemoselective pyridinium formation, this method allows benzyl primary amines to be efficiently converted to di(hetero)arylmethanes. Excellent heteroaryl and functional group tolerance is observed, and a one-pot procedure enables benzylic amines to be converted to diarylmethanes directly.

ChemInform Abstract: Nickel Nanoparticles as Racemization Catalysts for Primary Amines.

By combining bases that are known to racemize benzylic amines with a nickel(II) salt, active nickel nanoparticles were obtained that can be used as catalysts in the racemization of both aliphatic and benzylic primary amines. The nanoparticles are stable in the ionic liquid tetrabutylammonium bromide and can complete most racemizations within a few hours with excellent selectivity. The problem of the incompatibility of the strongly reducing racemization catalyst and the enzymatic amine resolution catalyst was overcome by using a two-pot system with a biphasic racemization step. Consecutive contact of a nonane layer that contained the amine with the acylating enzyme and with the racemizing Ni nanoparticles in the ionic liquid allowed the 50 % amide yield limit of a kinetic resolution to be successfully surpassed.

Nickel Nanoparticles as Racemization Catalysts for Primary Amines

AbstractBy combining bases that are known to racemize benzylic amines with a nickel(II) salt, active nickel nanoparticles were obtained that can be used as catalysts in the racemization of both aliphatic and benzylic primary amines. The nanoparticles are stable in the ionic liquid tetrabutylammonium bromide and can complete most racemizations within a few hours with excellent selectivity. The problem of the incompatibility of the strongly reducing racemization catalyst and the enzymatic amine resolution catalyst was overcome by using a two‐pot system with a biphasic racemization step. Consecutive contact of a nonane layer that contained the amine with the acylating enzyme and with the racemizing Ni nanoparticles in the ionic liquid allowed the 50 % amide yield limit of a kinetic resolution to be successfully surpassed.

3,3′-diaryl-BINOL phosphoric acids as enantioselective extractants of benzylic primary amines

We report that 3,3'-diaryl-BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid-liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3'-positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV-Vis, and CD spectroscopy, which provided insight into the structure of the host-guest complex involved in extraction.

Heterogeneous Raney Nickel and Cobalt Catalysts for Racemization and Dynamic Kinetic Resolution of Amines

AbstractRaney metals were studied as heterogeneous catalysts for racemization and dynamic kinetic resolution (DKR) of chiral amines, as an alternative to metals like palladium or ruthenium. Both Raney nickel and cobalt were able to selectively racemize various chiral amines with high selectivity. In the racemization of benzylic primary amines, the minor formation of side products, e.g., secondary amines, can be suppressed by varying the hydrogen pressure. In the racemization of aliphatic amines over Raney catalysts, the selectivity is very high, with the enantiomeric amine as the sole product. DKR of racemic aliphatic amines can be performed with immobilized Candida antarctica lipase B and Raney nickel in one pot; for 2‐hexylamine, a yield of 95 % of the acetylated amide was achieved, with 97 % ee. Attention is devoted to the compatibility of the enzyme and the metal catalyst during the DKR. For benzylic primary amines, a two‐pot process is proposed in which the liquid is alternatingly shuttled between two vessels containing the solid racemization catalyst and the biocatalyst. After 4 such cycles, the amide of (R)‐1‐phenylethylamine was obtained with 94 % yield and more than 90 % ee.

The chemistry of synthetic receptors and functional group arrays. 13. The intramolecular salt effect

Ionic groups and salt bridges in the active sites of enzymes are thought to have important effects upon substrate reactivity. This paper describes the evaluation of an ion pair as an intramolecular effector of reaction rate for an addition reaction, the reaction of benzylic primary amines with methyl propynoate