Allylic Amides Research Articles

Overcoming catalytic bias

Metathesis reactions can be used to make carbon–carbon double bonds — bar one isomeric class. By using new catalysts and balancing out the stabilities of intermediates in the reaction, the elusive isomers can be made. See Article p.461 The Z-alkene bond is one of the most important chemical bonds in nature. Many natural products contain one or several Z alkenes, consisting of a double bond with two substituents at each end pointing in the same direction. The potency or function of these natural products disappears or changes significantly if the two substituents point in opposite directions — a structure called an E alkene. Convenient methods for the stereoselective synthesis of 1,2-disubstituted Z alkenes are scarce. Amir Hoveyda and colleagues now describe catalytic Z-selective cross-metathesis reactions of terminal enol ethers and allylic amides, previously used only in E-selective processes. The potential of this reaction is demonstrated by its use in syntheses of antioxidant plasmalogen phospholipids found in electronically active tissues and implicated in Alzheimer's disease, and the potent immunostimulant and antitumour agent KRN7000.

Catalytic Z-selective olefin cross-metathesis for natural product synthesis

Alkenes are found in a great number of biologically active molecules and are employed in numerous transformations in organic chemistry. Many olefins exist as E or higher energy Z isomers. Catalytic procedures for stereoselective formation of alkenes are therefore valuable; nonetheless, methods for synthesis of 1,2-disubstituted Z olefins are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and allylic amides, employed thus far only in E-selective processes; the corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. Transformations, promoted by catalysts that contain the highly abundant and inexpensive molybdenum, are amenable to gram scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. Utility is demonstrated by syntheses of anti-oxidant C18 (plasm)-16:0 (PC), found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000.

Iridium‐Catalyzed Asymmetric Intramolecular Allylic Amidation: Enantioselective Synthesis of Chiral Tetrahydroisoquinolines and Saturated Nitrogen Heterocycles

For the first time iridium catalysis has been used for the synthesis of chiral tetrahydroisoquinolines with excellent yields and high enantioselectivities (see scheme; cod=1,5-cyclooctadiene, DBU=1,8-diazabicyclo[5.4.0]undec-7-ene). These products are important chiral building blocks for the synthesis of biologically active compounds, in particular alkaloids.

Iridium‐Catalyzed Asymmetric Intramolecular Allylic Amidation: Enantioselective Synthesis of Chiral Tetrahydroisoquinolines and Saturated Nitrogen Heterocycles

Ausgezeichnete Ausbeuten und hohe Enantioselektivitäten zeichnen die Titelreaktion aus (siehe Schema; cod=1,5-Cyclooctadien, DBU=1,8-Diazabicyclo[5.4.0]undec-7-en). Als Produkte entstehen wichtige chirale Bausteine für die Synthese von biologisch aktiven Verbindungen wie den Alkaloiden.

Nickel-Catalyzed Annulative Synthesis of 1,2-Benzothiazine-1,1(2H)-dioxides

Based on previous work on the enantioselective synthesis of 3,4-dihydroisoquinolin-1(2H)-ones by nickel-catalyzed denitrogenative annulation of allenes to 1,2,3-benzotriazin-4(3H)-ones (M. Yamauchi, M. Morimoto, T. Miura, M. Murakami J. Am. Chem. Soc. 2010, 132, 54), Murakami and co-workers report the regio- and enantioselective synthesis of 3,4-dihydro-1,2-benzothiazine-1,1(2H)-dioxides 3 from 1,2,3,4-benzothiatriazine-1,1(2H)-dioxides 1. Ni(cod)2 as catalyst and (R)-quinap as ligand afforded stereoselectively the optically active products 3 along with small amounts of regioisomers 4. The reaction is compatible with various primary and secondary alkyl and aromatic groups R¹ on the nitrogen (except R¹ = t-Bu probably due to steric hindrance) as well as with a variety of allene substituents R³. The scope of R² variation was poorly evaluated. A mechanism involving oxidative addition of the N-N bond to nickel(0) and extrusion of N2 to form a five-membered azanickelacycle, followed by allene insertion and allylic amidation at the more substituted carbon is assumed.

ChemInform Abstract: Organoselenium- and Proton-Mediated Cyclization Reactions of Allylic Amides and Thioamides. Syntheses of 2-Oxazolines and 2-Thiazolines.

A variety of allylic amides and thioamides were treated with phenylselenenyl bromide in chloroform to give, via 5-exo cyclization, 2-oxazolines and 2-thiazolines, respectively, carrying a (phenylselenenyl)methyl substituent in the 5-position. In some cases (N-crotyl- and N-cinnamylamides/thioamides), dihydro-1,3-oxazines/-thiazines were formed via 6-endo cyclization. The phenylselenenyl group of the cyclofunctionalization products was slowly eliminated by treatment with m-chloroperbenzoic acid to introduce unsaturation in the resulting oxazoline/thiazoline. Reductive removal of the phenylselenenyl group was effected by treatment with triphenyltin hydride. This reaction was sometimes accompanied by a rearrangement of the heterocyclic ring. Proton-induced cyclizations of allylic thioamides to give 2-thiazolines was slowly but efficiently effected in boiling toluene containing a catalytic amount of p-toluenesulfonic acid

Nickel-Catalyzed Denitrogenative Annulation Reactions of 1,2,3-Benzotriazin-4(3H)-ones with 1,3-Dienes and Alkenes

1,2,3-Benzotriazin-4(3H)-ones react with 1,3-dienes in the presence of a nickel(0)/phosphine complex to give a variety of 3,4-dihydroisoquinolin-1(2H)-ones. Oxidative insertion of nickel(0) into the triazinone moiety prompts extrusion of dinitrogen to give a five-membered ring azanickelacyclic intermediate. Subsequent insertion of 1,3-dienes into the nickel-carbon bond followed by allylic amidation affords 3,4-dihydroisoquinolin-1(2H)-ones. Alkenes also undergo insertion into the five-membered ring azanickelacyclic intermediate, and subsequent reductive elimination gives 3-substituted 3,4-dihydroisoquinolin-1(2H)-ones.

Efficient Iron-Catalyzed Tsuji-Trost Coupling Reaction of Aromatic Allylic Amides through a sp³-Carbon-Nitrogen Breaking

The catalytic activation of sp 3 -carbon-nitrogen of allylic amides is generally difficult because of the inefficient leaving-group ability of the amide group. In this article, we have discovered for the first time that FeCl 3 -catalyzed Tsuji-Trost coupling reaction of aromatic allylic amides with active methylene compounds, cyclohexanone, and allytrimethylsilane work efficiently under mild conditions.

Synthesis and applications of a chiral-oxygenated 3-chloro-3,6-dihydro-2 H-pyran obtained under Overman rearrangement conditions

A chlorinated side product was formed under Overman rearrangement conditions from a trichloroacetimidate along with the expected allylic amide. The chlorinated product derived from a hex-2-enopyranoside was obtained in a totally stereoselective manner, and it can be a useful synthetic intermediate for chlorinated sugars. In order to improve the isolated yields of either the expected Overman rearrangement product or the chlorinated compound, we carried out a thorough study on the experimental conditions. The application of the latter for the synthesis of potential calpain inhibitors is also reported.

Molecular iodine-catalysed amidation reaction of secondary benzylic and allylic alcohols with carboxamides or sulfonamides

A highly efficient method for the C–N bond formation via 2 mol% of molecular iodine-catalysed amidation reaction of benzylic and allylic alcohols with carboxamides or sulfonamides in MeCN is described, giving the corresponding substituted amides and allylic amides in moderate to excellent yields. The significan features of the procedure include mild and metal-free reaction conditions, operational simplicity, inexpensive reagents, short reaction time, and good yields.

Enantioselective, Iridium-Catalyzed Monoallylation of Ammonia

Highly enantioselective, iridium-catalyzed monoallylations of ammonia are reported. These reactions occur with electron-neutral, -rich, and -poor cinnamyl carbonates, alkyl and trityloxy-substituted allylic carbonates, and dienyl carbonates in moderate to good yields and excellent enantioselectivities. This process is enabled by the use of an iridium catalyst that does not require a Lewis acid for activation and that is stable toward a large excess of ammonia. This selective formation of primary allylic amines allows for one-pot syntheses of heterodiallylamines and allylic amides that are not otherwise accessible via iridium-catalyzed allylic amination without the use of blocking groups and protective group manipulations.

Palladium complexes of bis(acyclic diaminocarbene) ligands with chiral N-substituents and 8-membered chelate rings

Reaction of cis-dichloridobis( p-trifluoromethylphenylisocyanide)palladium(II) with N, N′-bis[( R)-1-phenylethyl]-1,3-diaminopropane afforded an enantiomerically pure, C 1-symmetric bis(acyclic diaminocarbene)PdCl 2 complex in 41% yield. The X-ray crystal structure of the complex revealed that three of the four carbene nitrogens are twisted out of conjugation with the carbene units, apparently as a result of steric interactions between one phenyl group and the propylene backbone of the chelate. A similar reaction with N, N′-bis[( R)-1-(1-naphthyl)ethyl]-1,3-diaminopropane did not lead to an isolable bis(carbene) complex, instead forming significant amounts of bis(ammonium) salt as a decomposition product. However, reaction of the same palladium isocyanide precursor with a mixture of all diastereomers of N, N′-bis[1-(1-naphthyl)ethyl]-1,3-diaminopropane provided an achiral, C s-symmetric palladium bis(acyclic diaminocarbene) complex derived exclusively from the ( R, S) diamine in 20% yield. An X-ray structure showed that the ( R, S) stereochemistry allows the bulky naphthyl groups to adopt an orientation that avoids steric interactions with the backbone that likely lead to the instability of the homochiral analogue. The two palladium carbene complexes catalyzed the aza-Claisen rearrangement of an allylic imidate to an allylic amide in 24–34% yield, with an enantiomeric excess of 8% ee for the [( R)-1-phenylethyl]-substituted complex.

Complementary Reactions of Allylic Carbamates Using Palladium(II): Formation of Oxazolidinones or Allylic Amides from a Common Precursor

The use of palladium to effect two different reactions on a commonstarting material is presented. With a copper oxidant, an aminohalogenationis achieved to produce oxazolidinones. When the copper is absent,a [3,3]-sigmatropic rearrangement takes place toproduce allylic amides.

Hydrolytic Deallylation of N‐Allyl Amides Catalyzed by PdII Complexes

AbstractHydrolytic deallylation of N‐allyl amides to give amides and propanal can be achieved with PdII catalysts. The optimized catalyst consists of Pd(OCOCF3)2 and 1,3‐bis(diphenylphosphanyl)propane (DPPP). Several kinds of open‐chain N‐allyl amides and N‐allyl lactams undergo hydrolytic deallylation to give the corresponding amides and lactams in good to high yield. A mechanism which includes isomerization to enamides and subsequent hydrolysis is proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Ferrocenylimidazoline palladacycles as efficient catalysts for the aza‐Claisen rearrangement reaction of allylic imidates

AbstractChloride‐bridged palladacycle dimers 1 have been evaluated as catalysts for the aza‐Claisen rearrangement of allylic imidates 2 to the corresponding allyl amides 3. Cyclopalladated complexes 1b–e bearing electron‐donating substituents on imidazoline ring were identified as being superior catalysts because excellent yields were obtained without using silver salts for activation. In addition, a correlation between substituents on the imidazoline ring and catalytic activity of palladacycles was established. The electron‐deficient ligands and good solubility of catalysts in the reaction solution increase the catalytic activity. Copyright © 2008 John Wiley & Sons, Ltd.

ChemInform Abstract: Iridium(I)‐Catalyzed Regio‐ and Enantioselective Allylic Amidation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Chiral Palladium Bis(acyclic diaminocarbene) Complexes as Enantioselective Catalysts for the Aza-Claisen Rearrangement

Palladium complexes of chiral bis(acyclic diaminocarbene) ligands with seven-membered chelate rings catalyze the aza-Claisen rearrangement of an allylic benzimidate to an allylic amide with moderate yields and enantioselectivities of 30–59% ee. The promotion of electrophilic catalysis by complexes of these ligands highlights their distinct stereoelectronic properties relative to those of common bis(N-heterocyclic carbenes).

Copper-Catalyzed Amidation with Chloramine T

The functionalization of hydrocarbons via a direct C-H amination is a highly attractive synthetic transformation. The method reported herein is remarkably simple and uses only inexpensive, commercially available reagents and catalysts. Good yields of products are obtained from benzylic substrates as well as from some cyclic ethers. Alkenes undergo amidochlorination along with allylic amidation. The products can be reductively deprotected to the corresponding benzyl­amines.

Iridium(I)-Catalyzed Stereospecific Decarboxylative Allylic Amidation of Chiral Branched Benzyl Allyl Imidodicarboxylates

Ir(I)-catalyzed decarboxylative allylic amidation of chiral branched benzyl allyl imidodicarboxylates has been shown to proceed with complete retention of enantiomeric purity and configuration. The transformation is stereospecific and appears to be quite general, accommodating a wide range of R groups.

Iridium(I)-catalyzed regio- and enantioselective allylic amidation

Ir(I)-catalyzed intermolecular allylic amidation of ethyl allyl carbonates with soft nitrogen nucleophiles under completely ‘salt-free’ conditions is described. A combination of [Ir(COD)Cl] 2, a chiral phosphoramidite ligand L ∗, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines. The developed reaction was conveniently utilized in the asymmetric synthesis of N-Boc protected α- and β-amino acids as well as (−)-cytoxazone.