High Anti Selectivity Research Articles

High anti Diastereoselectivity in a Tandem Oxyhomologation-Coupling Protocol for the Preparation of Amides and Peptides Incorporating α-Hydroxy β-Amino Acids.

The one-pot MAC (Masked Acyl Cyanide) reaction is used to perform the tandem oxyhomologation reaction of N,N-dibenzyl-l-phenylalaninal and coupling with nitrogen nucleophiles to provide a wide selection of amide and peptide derivatives of (2S,3S)-allophenylnorstatin in generally good yields and with high anti selectivity, often with dr >98:2. The procedure works equally well with other selected N,N-dibenzyl α-amino aldehydes, and is used to achieve a very short synthesis of (2S,3S,S)-epibestatin.

Anti-Selective Synthesis of Substituted β-Homoprolines by Rhodium Alkyl Nitrene C–H Insertion

AbstractA range of β-homoprolines was prepared with high anti-selectivity. An intramolecular C–H insertion reaction involving a rhodium alkyl nitrene is a key step in the ring construction. The carboxylic acid in the products can serve as a springboard for further downstream transformations.

Regio- and Stereo-controlled Addition Reaction of Aminoallylic Stannanes to Aldehydes Mediated by Germanium Dichloride

A GeCl2-mediated addition reaction of α-(N-phthaloylamino)allylic stannane to aldehydes was achieved to give 1,2-amino alcohol derivatives in high anti-selectivity. Various types of aromatic and aliphatic aldehydes were applicable. The synthesized N-phthaloylamino alcohols were smoothly transformed to aminoalcohols by conventional methods with no loss of stereochemistry.

Selective Synthesis of Spirooxindoles by an Intramolecular Heck-Mizoroki Reaction.

We report a highly diastereoselective synthesis of cyclopentene-spirooxindole derivatives via an intramolecular Heck-Mizoroki reaction using aryl bromides as precursors. The reactions were performed under dry conditions or in a DMF-water system. This protocol can be useful to introduce several functionalities to the aromatic nucleus of the spirooxindoles. DFT calculations were performed to rationalize the high antiselectivity. A functionalized spiroproduct was transformed into a cyclic amino acid derivative.

Stereoselective synthesis of vic-halohydrins and an unusual Knoevenagel product from an organocatalyzed aldol reaction: A non-enamine mode

Stereoselective synthesis by an aldol reaction between chloroacetone and aldehyde was studied using a synthesized chiral organocatalyst and triethylamine. The reaction gave α-chloro-β-hydroxy ketones in excellent yield with high anti selectivity and enantioselectivity. The chiral organocatalyst was also used in the Knoevenagel reaction, which gave α-cyano-β-hydroxy ketones at a low temperature and the usual Knoevenagel product at a high temperature. Both products were obtained in good to moderate yield with good anti selectivity in the case of α-cyano-β-hydroxy ketone derivatives.

Catalytic Organic Reactions on the Surface of Silver(I) Oxide in Water

Abstract We have developed Ag2O-catalyzed allylation reactions of aldehydes with allylsilanes in water, providing homoallylic alcohols in high yields with high anti-selectivities. It was found that the reactions proceeded not in the water solution but on the surface of Ag2O. We could reduce the amount of the catalyst to less than 0.01 mol %. Moreover, an asymmetric allylation reaction was performed in water with high yield and moderate enantioselectivity by using a chiral phosphine ligand.

ChemInform Abstract: Halocarbocyclization versus Dihalogenation: Substituent Directed Iodine(III) Catalyzed Halogenations.

AbstractThe introduced catalyst enables chemoselective dibromination of alkenes and alkynes and dichlorination of alkenes with high anti‐selectivity.

One-pot synthesis of vicinal aminoalkanols from sugar aldehydes

A novel synthetic method of carbohydrate derived vicinal aminoalcohols, from sugar aldehydes and bromonitroalkanes, has been developed. It involves an indium-catalyzed one-pot Henry reaction and nitro group reduction, and proceeds with a remarkably high anti-selectivity. The reaction of the intermediate aminoalcohols with alkylating agents furnished the corresponding carbohydrate-based tertiary aminoalcohols with excellent stereoselectivity. This very simple methodology allows easy access to families of N,N-dialkylated vicinal aminoalkanols, useful intermediates in the synthesis of derivatives of biological interest and sugar-based stereodifferentiating agents for asymmetric catalysis.

Highly Efficient Organosuperbase‐Catalyzed Mannich‐type Reactions of Sulfonylimidates with Imines: Successful Use of Aliphatic Imines as Substrates and a Unique Reaction Mechanism

First walk, then run! Highly efficient organosuperbase-catalyzed Mannich-type reactions of sulfonylimidates with readily prepared Boc-protected imines have been developed. The desired products were obtained in high yield and with high anti selectivity. Mechanistic studies show an induction period for the catalyzed reaction, and that the organosuperbase works as an initiator.

Indium‐Mediated Aza‐Henry Reaction of Imines: Access to 2‐Nitroamines

AbstractA new method has been developed to obtain 2‐nitroamines by an indium‐promoted reaction of bromonitromethane with a variety of imines. On the strength of these results, the reaction was also performed with 2‐bromo‐2‐nitropropanes to afford 2,2‐dialkyl‐2‐nitroamines. Moreover, the indium‐mediated reaction of 1‐bromo‐1‐nitroethane and imines afforded 1‐methyl‐2‐nitroamines with remarkably high anti selectivity. The use of chiral sugar‐derived imines furnished the corresponding 2‐nitroamines with excellent stereoselectivity.

Highly diastereoselective Mannich-type reaction of titanium enolate derived from 2′-hydroxypropiophenone

Mannich-type addition of the titanium enolate derived from 2′-hydroxypropiophenone to N-tosylimines provided the corresponding β-aminoketones in good to excellent yields (60%–90%) and with >99 : <1 anti diastereoselectivity. A model for synthesis of anti β-aminoketone as a predominant isomer based on the titanium enolate has been developed. High anti selectivity is not independent of the electron-donating and electron-withdrawing groups on the phenyl ring of the N-tosylimines. Noteworthy is the observation that the influence of a second Lewis acid on the Mannich-type reaction based on the titanium enolate is opposite to that obtained from other titanium enolates reported. A reasonable mechanism has been proposed to explain the high anti diastereoselectivity and the effect of a second Lewis acid on yield.

ChemInform Abstract: Catalytic Silicon‐Mediated Carbon—Carbon Bond‐Forming Reactions of Unactivated Amides.

In the presence of catalytic amounts of trialkylsilyl triflate and triethylamine, unactivated amides react with imines to afford the corresponding Mannich-type adducts in high yields with high anti selectivities. While silicon enolates have been widely used in organic synthesis for four decades, this is the first example of the catalytic use of the silicon species, to the best of our knowledge. Moreover, it is noteworthy that unactivated simple amides bearing α-protons that are less acidic than those of ketones and aldehydes can be successfully used in catalytic direct-type addition reactions. Finally, a preliminary trial of an asymmetric catalytic version was conducted and showed promising enantioselectivity of the desired product.

ChemInform Abstract: Highly Diastereo‐ and Enantioselective Organocatalytic Michael Addition of α‐Ketoamides to Nitroalkenes.

AbstractThe method furnishes Michael adducts with high anti selectivity (<90% d.e.) and enantioselectivity.

Highly enantioselective synthesis of anti aryl β-hydroxy α-amino esters via DKR transfer hydrogenation

An efficient preparation of highly enantiomerically enriched aryl β-hydroxy α-amino esters via dynamic kinetic resolution (DKR), asymmetric transfer hydrogenation of α-amino β-keto esters is described. The anti β-hydroxyl α-amino esters were obtained both in high yields and high diasteroselectivity. The observed high anti selectivity is inconsistent with the previous results in literature. The absolute stereochemistry of the aryl β-hydroxy α-amino esters was unambiguously confirmed via chemical derivatization as well as Vibrational Circular Dichroism (VCD) techniques.

Catalytic Silicon-Mediated Carbon−Carbon Bond-Forming Reactions of Unactivated Amides

In the presence of catalytic amounts of trialkylsilyl triflate and triethylamine, unactivated amides react with imines to afford the corresponding Mannich-type adducts in high yields with high anti selectivities. While silicon enolates have been widely used in organic synthesis for four decades, this is the first example of the catalytic use of the silicon species, to the best of our knowledge. Moreover, it is noteworthy that unactivated simple amides bearing α-protons that are less acidic than those of ketones and aldehydes can be successfully used in catalytic direct-type addition reactions. Finally, a preliminary trial of an asymmetric catalytic version was conducted and showed promising enantioselectivity of the desired product.

Dinuclear Nickel Catalyst in 1,4-Addition of α-Ketoanilides to Nitroalkenes

The use of α-keto esters as nucleophiles in conjugate addition is uncommon because of their high electrophilicity and thus pre­disposition to self-condensation. This work describes an application of a dinuclear nickel catalyst to address this problem, yielding syn products in moderate to good yields and enantioselectivities. This work is preceded by a report from the Sodeoka group (J. Am. Chem. Soc, 2010, 132, 4036), where similar products are obtained in high anti selectivity.

ChemInform Abstract: Stereoselective Synthesis of Enantiomerically Pure 4,5-Disubstituted Pyrrolidinones from β-Amino Esters.

Abstract α-Alkylation of N -tosyl-protected β-amino esters with LDA as the base led to high anti selectivity for the newly formed C–C bond. The α-alkylated β-amino esters were further transformed to enantiomerically pure 4,5-disubstituted pyrrolidinones through hydrolysis, diazotization, and Wolf rearrangement under AgO 2 CPh/Et 3 N/dry THF conditions.

(S)‐Indoline‐3‐Carboxylic Acid: A New Organocatalyst for the Anti Mannich‐Type Reaction

Enantiopure indoline-3-carboxylic acid is synthesized using an enzymatic kinetic resolution as a key step (E≫100). It is applied as an organocatalyst in Mannich-type reactions, which proceed with high anti selectivity at low temperatures, affording the products in moderate to good yields and in excellent enantiomeric excess.

Catalytic Mannich-Type Reactions of Sulfonylimidates

Abstract A novel nucleophile, sulfonylimidate, has been successfully employed in Mannich-type reactions. Due to electron-withdrawing property of sulfonyl group of sulfonylimidate, the acidity of α-proton is enhanced so that sulfonylimidate bearing no activating functional group at α-position is deprotonated by relatively weak base. DBU-catalyzed reactions of sulfonylimidates with protected imines in DMF provided the adducts in high yields with high anti selectivity. This reaction represents a wide substrate scope and a high catalytic turnover. A thorough kinetic study revealed that rate-determining step is most likely deprotonation step in case of Ts-imidate. Alkali earth metal alkoxide and its HMDS salt also catalyze Mannich-type reactions of sulfonylimidates. The reactions catalyzed by Mg(OtBu)2 in DMF provided the adducts with high anti selectivity, while those catalyzed by [Sr(HMDS)2]2 gave syn selectivity. The asymmetric variant of Mannich-type reaction of sulfonylimidate was also achieved. Several transformations of sulfonylimidates to other functional groups were also demonstrated. Finally, direct-type catalytic formation of β-amino acid ester from aldehyde and sulfonylimidate was achieved via in situ formation of sulfonylimine and DBU-assisted hydrolysis of sulfonylimidate.

Diastereoselective Acid-Catalyzed Ritter Reaction

In a rare study of carbenium ions ­inducing facial selectivity in SN1 reactions, an asymmetric Ritter reaction is described for chiral secondary benzylic alcohols. Using trifluoro-methanesulfonic acid, amides with high anti selectivity are produced. In contrast, the use of dinitrobenz­enesulfonic acid provides syn-selective products.