Primary Allylic Amines Research Articles

Primary Allylic Amine Synthesis via Pd-Catalyzed Direct Amination of Allylic Alcohols with Ammonium Acetate.

Pd/DPEphos-catalyzed direct amination of allylic alcohols with readily available ammonium acetate as a nitrogen source provides access to convenient and scalable syntheses of primary allylic amines with high monoallylation selectivity. Mechanistic studies revealed that ammonium acetate functions as a Brønsted acid to activate the hydroxyl groups and inhibit overreaction.

Synthesis of Allylic Amines by Asymmetric Transfer Hydrogenation of α,β-Unsaturated N-(tert-Butylsulfinyl)imines.

Primary allylic amines with enantiomeric excesses from 97 to >99% were prepared by asymmetric transfer hydrogenation of α,β-unsaturated N-(tert-butylsulfinyl)ketimines followed by removal of the sulfinyl group. The effect caused by different substituents at the C═C bond and at the iminic carbon atom on the chemoselectivity of the reduction was studied. The desired enantiomer of the final allylic amine can be synthesized by choosing the sulfinyl group with the appropriate absolute configuration.

Rearrangement Reactions Leading to Optically Active α,α‐Disubstituted Primary Allylamines

Synthetic routes to α,α‐disubstituted allylamines have been examined. Racemic compounds were conveniently prepared by thermal Overman rearrangements of primary allylic alcohols with trisubstituted double bonds, but rearrangement of these substrates using the only commercially available compound known to catalyze enantioselective Overman rearrangements, the cobalt oxazoline palladacycle (R)‐COP‐Cl, failed. Instead, optically active secondary allylic alcohols with trisubstituted double bonds, obtained by Corey–Bakshi–Shibata reduction of the corresponding methyl ketones, were synthesized and converted into α,α‐disubstituted allylamines through a thermal Overman rearrangement or an allylic‐cyanate‐to‐isocyanate rearrangement. High chirality transfer (90–99 %) was obtained for both reaction sequences, but the yields were greatly improved when the allylic‐cyanate‐to‐isocyanate rearrangement was used.

Palladium-Catalyzed Stereospecific Allylation of Nitroacetates with Enantioenriched Primary Allylic Amines

An unprecedented stereospecific allylation reaction of nitroacetates with enantioenriched primary allylic amines has been developed. A range of nitroacetates smoothly underwent allylation with enantioenriched primary allylic amines in the presence of a palladium catalyst and boric acid followed by one-pot decarboxylation to afford structurally diverse homoallylic nitro compounds in good to excellent yields with excellent retention of configuration. On the other hand, the allylation followed by denitronation provided a facile synthetic route to optically active β-chiral γ,δ-unsaturated esters.

ChemInform Abstract: Enantioselective Construction of C‐Chiral Allylic Sulfilimines via the Iridium‐Catalyzed Allylic Amination with S,S‐Diphenylsulfilimine: Asymmetric Synthesis of Primary Allylic Amines.

We have devised a highly regio- and enantioselective iridium-catalyzed allylic amination reaction with the sulfur-stabilized aza-ylide, S,S-diphenylsulfilimine. This process provides a robust and scalable method for the construction of aryl-, alkyl- and alkenyl-substituted C-chiral allylic sulfilimines, which are important functional groups for organic synthesis. Additionally, the combination of the allylic amination with an in situ deprotection of the sulfilimine constitutes a convenient one-pot protocol for the construction of chiral nonracemic primary allylic amines.

ChemInform Abstract: Deammoniative Condensation of Primary Allylic Amines with Nonallylic Amines.

AbstractThe first examples of an efficient deammoniative condensation of primary allylic amines with nonallylic amines are given.

Enantioselective construction of C-chiral allylic sulfilimines via the iridium-catalyzed allylic amination with S,S-diphenylsulfilimine: asymmetric synthesis of primary allylic amines.

We have devised a highly regio- and enantioselective iridium-catalyzed allylic amination reaction with the sulfur-stabilized aza-ylide, S,S-diphenylsulfilimine. This process provides a robust and scalable method for the construction of aryl-, alkyl- and alkenyl-substituted C-chiral allylic sulfilimines, which are important functional groups for organic synthesis. Additionally, the combination of the allylic amination with an in situ deprotection of the sulfilimine constitutes a convenient one-pot protocol for the construction of chiral nonracemic primary allylic amines.

Kinetic resolution of primary allylic amines via palladium-catalyzed asymmetric allylic alkylation of malononitriles.

A range of primary allylic amines were resolved with selectivity factors of up to 491 through [Pd(allyl)Cl]2/(S)-BINAP-catalyzed and mesitylsulfonyl hydrazide-accelerated asymmetric allylic alkylation of malononitriles involving enantioselective C-N bond cleavage under aerobic conditions. Moreover, the reaction proved useful for the asymmetric synthesis of α-branched allyl-substituted malononitriles with high enantiopurity.

ChemInform Abstract: Catalytic Allylation of Hypophosphorous Acid and H‐Phosphinic Acids with Primary Allylic Amines.

AbstractOptimized conditions render possible the efficient allylation of hypophosphorous acid and H‐phosphinic acids with various primary amines.

A new entry to azomethine ylides from allylic amines and glyoxals: shifting the reliance on amino ester precursors.

The first examples of azomethine ylides derived from allylic amine and glyoxal precursors are reported. The condensation of primary allylic and α-aryl amines with glyoxylates or α-aryl glyoxals affords conjugated azomethine ylides that undergo facile [3 + 2] cycloaddition, providing 5-alkenyl pyrrolidine cycloadducts that cannot be accessed through the classical use of amino esters as ylide precursors.

Deammoniative Condensation of Primary Allylic Amines with Nonallylic Amines

AbstractAn unprecedented deammoniative condensation reaction of primary allylic amines with nonallylic amines has been developed through CN bond cleavage. In the presence of 5 mol% palladium diacetate, 10 mol% 1,4‐bis(diphenylphosphino)butane (dppb), and 5 mol% p‐toluenesulfonic acid (TsOH), a range of α‐unbranched primary allylic amines smoothly underwent deammoniative condensation with nonallylic amines in an α‐selective fashion to give structurally diverse secondary and tertiary amines in good to excellent yields and E selectivity. Replacing dppb with racemic 2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl (BINAP) permitted the deammoniative condensation of enantioenriched α‐chiral primary allylic amines with nonallylic amines to proceed with complete retention of configuration. Electrospray ionization (ESI) mass spectrometric analysis of the reaction mixture permitted the identification of some π‐allylpalladium intermediates, and plausible mechanisms have been proposed to account for the regioselectivity and stereospecificity of the deammoniative condensation reaction.

Catalytic stereospecific allylation of protected hydrazines with enantioenriched primary allylic amines

An unprecedented allylation reaction of protected hydrazines with enantioenriched allylic amines has been developed in a stereospecific manner with net stereoretention. A wide variety of protected hydrazines underwent palladium/acid-catalyzed allylation with highly enantioenriched primary allylic amines to give structurally diverse N-allylhydrazines in moderate to excellent yields with extremely high regioselectivity and complete retention of the configuration. Importantly, the reaction exhibits high atom-economy by yielding ammonia as the sole byproduct.

Catalytic Allylation of Hypophosphorous Acid and H‐Phosphinic Acids with Primary Allylic Amines

AbstractPrimary allylic amines serve as suitable allylic electrophiles for the allylation reactions of hypophosphorous acid and H‐phosphinic acids. In the presence of tris(dibenzylideneacetone)dipalladium(0) ([Pd2(dba)3], 0.1 mol %) and Xantphos (0.2 mol %), aqueous hypophosphorous acid was allylated by α‐unbranched primary allylic amines in a highly regioselective fashion to give structurally diverse allylic H‐phosphinic acids in good to excellent yields with exclusive E selectivity. Moreover, increasing the catalyst loading to 1 mol % and adding aqueous phosphoric acid (1.2 equiv.) permitted the allylation of H‐phosphinic acids with α‐unbranched primary allylic amines to proceed to give disubstituted phosphinic acids in good to excellent yields.

ChemInform Abstract: Non‐enzymatic Acylative Kinetic Resolution of Primary Allylic Amines.

AbstractA non‐enzymatic acetyl‐transfer kinetic resolution of primary amines (I), (IV), (VI), and (VIII) is reported.

Palladium-catalyzed aerobic oxidative coupling of enantioenriched primary allylic amines with sulfonyl hydrazides leading to optically active allylic sulfones

A range of highly enantioenriched primary allylic amines underwent palladium-catalyzed oxidative coupling with sulfonyl hydrazides open to air at room temperature to give structurally diverse allylic sulfones in moderate to excellent yields with excellent retention of ee.

Correction to “Stereospecific Substitution of Allylic Alcohols To Give Optically Active Primary Allylic Amines: Unique Reactivity of a (P,alkene)Ir Complex Modulated by Iodide”

Correction to “Stereospecific Substitution of Allylic Alcohols To Give Optically Active Primary Allylic Amines: Unique Reactivity of a (P,alkene)Ir Complex Modulated by Iodide”

Catalytic Allylation of Stabilized Phosphonium Ylides with Primary Allylic Amines

A range of ketone-stabilized phosphonium ylides were allylated with high regioselectivity by primary allylic amines in the presence of 5 mol % Pd(PPh3)4 and 10 mol % B(OH)3, and subsequent one-pot Wittig olefination gave structurally diverse α,β-unsaturated ketones in good to excellent overall yields with excellent E selectivity. The one-pot allylation/olefination reaction was extended to ester- and nitrile-stabilized phosphonium ylides by replacing B(OH)3 with TsOH, and the corresponding α,β-unsaturated esters and nitriles were obtained in moderate overall yields.

Overman Rearrangement of Fluorinated Allylic Alcohols as a Key Step for the Synthesis of Glycyldecylamide (GDA) Mimics

O verman rearrangements based on secondary 2-fluoroallylic alcohols were performed to synthesize fluorinated primary allylic amines for the first time. The vinylic fluorine atom dramatically slows down the reaction rate. Long alkyl chain fluorinated allylic amine, which is a mimic of a drug against schizophrenia, was further coupled with Boc-protected phenyl glycine, forming a Gly-Phe peptide mimic.

Lewis Acid Mediated Vinyl‐Transfer Reaction of Alkynes to N‐Alkylimines by Using the N‐Alkyl Residue as a Sacrificial Hydrogen Donor

A variety of N-alkyl-α,α-dichloroaldimines were vinylated by terminal acetylenes in the presence of Lewis acids such as In(OTf)3 or BF3 ⋅OEt2 and hexafluoroisopropanol (HFIP) as an additive. The reaction proceeds at ambient temperature and leads to geometrically pure allylic β,β-dichloroamines. This approach is complementary to previously reported transition-metal-catalyzed vinyl-transfer methods, which are not applicable to aliphatic imines and are restricted to imines that contain an electron-withdrawing nitrogen substituent. In the present approach, terminal alkynes were used as a source of the vinyl residue, and the N-alkyl moiety of the imine acts as a sacrificial hydrogen donor. The additional advantage of this methodology is the fact that no external toxic or hazardous reducing agents or molecular hydrogen has to be used. This new methodology nicely combines a C(sp(2) )C(sp) bond formation, hydride transfer, and an unusual cleavage of an unactivated CN bond, thereby giving rise to functionalized primary allylic amines. A detailed experimental study supported by DFT calculations of the mechanism has been done.

ChemInform Abstract: Direct Substitution of Primary Allylic Amines with Sulfinate Salts.

AbstractThe process is applied to a broad spectrum of substrates where high regioselectivity is observed.