N-Boc Aldimines Research Articles

Synthesis of β-Allenylamines by Addition of Chloroprene Grignards to N-Boc Imines.

The γ-selective addition of chloroprene Grignards to aromatic N-Boc aldimines enabled by 2,2'-dimorpholinodiethyl ether (DMDEE) yields the corresponding N-Boc protected β-allenylamines in good yields and regioselectivities. Transmetalation to zinc bromide also allows the addition of chloroprene Grignard to aliphatic aldimines in good yields. The obtained β-allenylamines were shown to be easily deprotected under acidic conditions and can be subjected to various transformations to access complex molecules.

Modular synthesis of chiral 1,2-dihydropyridines via Mannich/Wittig/cycloisomerization sequence that internally reuses waste

1,2-Dihydropyridines are valuable and reactive synthons, and particularly useful precursors to synthesize piperidines and pyridines that are among the most common structural components of pharmaceuticals. However, the catalytic enantioselective synthesis of structurally diverse 1,2-dihydropyridines is limited to enantioselective addition of nucleophiles to activated pyridines. Here, we report a modular organocatalytic Mannich/Wittig/cycloisomerization sequence as a flexible strategy to access chiral 1,2-dihydropyridines from N-Boc aldimines, aldehydes, and phosphoranes, using a chiral amine catalyst. The key step in this protocol, cycloisomerization of chiral N-Boc δ-amino α,β-unsaturated ketones recycles the waste to improve the yield. Specifically, recycling by-product water from imine formation to gradually release the true catalyst HCl via hydrolysis of SiCl4, whilst maintaining a low concentration of HCl to suppress side reactions, and reusing waste Ph3PO from the Wittig step to modulate the acidity of HCl. This approach allows facile access to enantioenriched 2-substituted, 2,3- or 2,6-cis-disubstituted, and 2,3,6-cis-trisubstituted piperidines.

Enantioselective hydrophosphonylation of N-Boc imines using chiral guanidine-thiourea catalysts.

The enantioselective hydrophosphonylation of N-Boc imines was investigated using a new family of pseudo-symmetric guanidine-thiourea catalysts, providing α-amino phosphonates in moderate to high yields with good enantioselectivity. The catalyst was heterogenized by polymerization with styrene and the resulting catalyst was applied to reactions under continuous-flow conditions.

Silver-Catalyzed Enantioselective Mannich Reaction of Diazoacetate Esters with N-Boc Aldimines.

The highly enantioselective Mannich reaction of diazoacetate esters with N-Boc aldimines catalyzed by silver(I) triflate in the presence of (R)-DM-SEGPHOS is reported. The reaction is broad in scope with respect to the (hetero)aromatic aldehyde-derived aldimine and tolerates significant variability of the diazoacetate ester component. Yields and enantioselectivities are good to excellent, and the reaction can be performed on a gram scale with catalyst loadings as low as 1 mol %.

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

A highly diastereo- and enantioselective Mannich-type reaction of 3-aryloxindoles with N-Boc aldimines was achieved under the catalysis of axially chiral ammonium betaines. This catalytic method provides a new tool for the construction of consecutive quaternary and tertiary stereogenic carbon centers on biologically intriguing molecular frameworks with high fidelity.

Asymmetric additions of thioglycolates and N-Boc aldimines catalyzed by a bifunctional tertiary-amine squaramide.

A highly enantioselective asymmetric addition reaction of thioglycolates and N-Boc aldimines was promoted by a bifunctional tertiary-amine squaramide catalyst. As a result, a number of chiral N,S-acetal derivatives were efficiently synthesized with good enantioselectivities.

Vinylogy in nitronates: utilization of α-aryl conjugated nitroolefins as a nucleophile for a highly stereoselective aza-Henry reaction.

The vinylogous reactivity of α,β-disubstituted nitroolefins was uncovered through the facile generation of the corresponding α-substituted vinylogous nitronates and their use in the development of a highly diastereo- and enantioselective aza-Henry reaction with N-Boc aldimines under the catalysis of chiral ammonium betaines. The novel vinylogous nitronates undergo stereoselective bond formation at the sterically encumbered α-position exclusively, allowing the construction of contiguous tertiary-quaternary stereogenic carbon centers.

ChemInform Abstract: Construction of Chiral Quaternary Carbon Center via Catalytic Asymmetric Aza‐Henry Reaction with α‐Substituted Nitroacetates.

The catalytic enantioselective aza-Henry reaction of N-Boc aldimines 2 and 2-nitropropionic acid ethyl ester 3 in the mixed solvents of toluene–saturated brine (10 : 1) was catalyzed by cinchona quaternary ammonium salts to form a new quaternary carbon center. High yields (up to 90%), and excellent enantioselectivities (up to 99% ee) and diastereoselectivity ratio (up to 22 : 1) were successfully obtained with mild conditions.

Enantioselective Copper-Catalyzed Reductive Coupling of Vinylazaarenes with N-Boc Aldimines

The diastereo- and enantioselective reductive coupling of vinylazaarenes with <i>N</i>-Boc aldimines is described. The reactions proceed using chiral copper–bisphosphine complexes in the presence of TMDS as a hydride source to give reductive coupling products in moderate to high enantioselectivities.

Construction of chiral quaternary carbon center via catalytic asymmetric aza-Henry reaction with α-substituted nitroacetates

The catalytic enantioselective aza-Henry reaction of N-Boc aldimines 2 and 2-nitropropionic acid ethyl ester 3 in mixed solvents were catalyzed by cinchona quaternary ammonium salts to form a new quaternary carbon center. High yields (up to 90%), excellent enantioselectivities (up to 99% ee) and diastereoselectivities ratio (up to 22 : 1) were successfully obtained with mild conditions.

Diastereo- and Enantioselective Pd(II)-Catalyzed Additions of 2-Alkylazaarenes to N-Boc Imines and Nitroalkenes

A chiral Pd(II)-bis(oxazoline) complex was found to be highly effective in promoting the first direct diastereo- and enantioselective addition of alkylazaarenes to N-Boc aldimines and nitroalkenes under mild conditions. Deprotection of Boc-protected products proceeded readily to provide amines in high yields.

Axially chiral phosphine–oxazoline ligands in silver(I)-catalyzed asymmetric Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran

Axially chiral phosphine–oxazoline ligand L6 was found to be a fairly effective chiral ligand in silver(I)-catalyzed asymmetric Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran to give the corresponding adducts in up to 97% yield, 7:1 dr and 86% ee (major diastereoisomer).

Catalytic asymmetric Mannich-type reactions of fluorinated ketoesters with N-Boc aldimines in the presence of chiral palladium complexes

The catalytic enantioselective Mannich reaction promoted by chiral palladium complexes is described. The treatment of α-fluoro-β-ketoesters with N-Boc-aldimines under mild reaction conditions afforded the corresponding β-aminated α-fluoro-β-ketoesters with excellent enantioselectivities (up to 99% ee).

Organocatalytic Enantioselective Mannich-Type Reactions of Fluorinated Keto Esters with N-Boc-Aldimines

The catalytic enantioselective Mannich reaction promoted by chiral bifunctional organocatalysts is described. The treatment of α-fluoro-β-keto esters with N-Boc aldimines under mild reaction conditions afforded the corresponding β-aminated α-fluoro-β-keto esters with excellent enantioselectivities (up to 98% ee).

Trimethylchlorosilane-promoted aza-Mannich reaction of enecarbamates and aldimines

A trimethylchlorosilane-promoted aza-Mannich reaction is reported utilizing enecarbamates as the nucleophile and aromatic N-Boc aldimines as the electrophile. A variety of nucleophiles and electrophiles are tolerated by the reaction conditions, delivering the adduct products in excellent yields with high E-stereoselectivities.

Palladium-catalyzed Asymmetric Mannich-type Reactions of α-Cyanoketones with N-Boc Aldimines

However, a highly enantioselective Mannich reaction of α- cyanoketones with simple imines remains elusive; although, if successfully promoted with a practically accessible chiral catalyst under air- and moisture-tolerant conditions, it could provide a highly attractive, convergent approach toward optically active β-amino nitriles. As part of research program related to the development of synthetic methods for the enantioselective construction of stereogenic carbon centers,

Organocatalytic Enantioselective Mannich-Type Reaction of Phosphorus Ylides: Synthesis of Chiral N-Boc-β-Amino-α-methylene Carboxylic Esters

The first asymmetric Mannich-type reaction of stabilized phosphorus ylides and N-Boc aldimines was described promoted by a readily available and recyclable chiral bisthiourea organocatalyst. Subsequent reaction with formalin smoothly provides N-Boc-β-amino-α-methylene carboxylic esters in a highly enantiomerically enriched form (up to 96% ee).

Organocatalytic and Highly Stereoselective Direct Vinylogous Mannich Reaction

The first direct asymmetric vinylogous Mannich (AVM) reaction of alpha,alpha-dicyanoolefins and N-Boc aldimines was described promoted by a simple chiral bifunctional thiourea-tertairy amine organocatalyst. The reaction was highly efficient (S/C up to 1000) and regio-, stereoselective (generally >99% de, 96 to >99.5% ee) at room temperature for a broad array of substrates. Enantiomerically pure delta-amino acid could be smoothly prepared from the adduct.

Asymmetric Catalytic Mannich Reactions Catalyzed by Urea Derivatives: Enantioselective Synthesis of β‐Aryl‐β‐amino Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric catalytic Mannich reactions catalyzed by urea derivatives: enantioselective synthesis of beta-aryl-beta-amino acids.

Highly enantioselective addition reactions between silyl ketene acetals and N-Boc aldimines are catalyzed by the thiourea-based catalyst 1c. Extraordinary scope is observed in this methodology with regard to the imine substrate, with aryl and heteroaromatic derivatives generally affording nearly quantitative yields of beta-amino ester product in up to 98% enantioselectivity.