Phosphazene Base-Catalyzed Intramolecular Hydroamidation of Alkenes with Amides.

A method for the synthesis of cyclic amides via phosphazene base-catalyzed intramolecular hydroamidation of amide alkenes was developed. The reaction using a catalytic amount of P4-base had a good functional group tolerance and a broad substrate scope and could also be used to synthesize lactam, cyclic urea, and oxazolidinone compounds. This catalytic system was expanded to a one-pot intramolecular hydroamidation and intermolecular hydroalkylation. Deuterium labeling and radical trapping experiments provided mechanistic insights into the catalytic cycle of the hydroamidation reaction.

General entry to asymmetric one-pot [N + 2 + n] cyclization for the synthesis of three- to seven-membered azacycloalkanes.

Enantio- and diastereoselective one-pot synthesis of three- to seven-membered cis-azaheterocycles was achieved using a triggered asymmetric conjugate addition reaction of lithium amide with an enoate, followed by alkylation of the resulting lithium enolate with α,ω-dihaloalkane and N-alkylation. Isomerization of cis-azaheterocycles with a base yielded the trans-product, constituting a one-pot synthesis of cis-azacycles and a two-step synthesis of trans-azacycles. The four-step asymmetric synthesis of nemonapride highlights the general utility of the method.

Radical one-pot α,ß-dual and ß-mono-oxymethylation of alkylidenemalonate.

Dimethylzinc-mediated radical conjugate addition reaction of dimethyl alkylidenemalonates with iodomethyl pivalate gave a high yield of the α,ß-dual oxymethylation product in one pot under air and the ß-pivaloyloxymethylation product under argon.

High performance of N-alkoxycarbonyl-imines in triethylborane-mediated tin-free radical addition.

Triethylborane-mediated tin-free radical alkylation of N-alkoxycarbonyl-imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, proceeded smoothly at a low temperature (-78 to -20 °C) to give the corresponding adducts in high yield. Although the formation of isocyanate was the major unfavorable reaction at room temperature, a one-pot conversion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.

Chiral N-heterocyclic carbene-copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides: steric and electronic effects on γ-selectivity.

Chiral N-heterocyclic carbene ligands were electronically and sterically tuned to improve γ-selectivity in copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides with several aryl Grignard reagents. High γ-selectivity was realized when either the aryl group of the Grignard reagent or the aryl group on the N-substituent of the carbene ligand was electron-deficient or when either the carbene ligand or allylic bromide was bulky. The results indicated that electron deficiency and steric hindrance of the initially formed σ-allyl copper intermediate enhance the rate of the reductive elimination to give γ-products as major isomers.

Stereoselective formal synthesis of (+)-allokainic acid via thiol-mediated acyl radical cyclization.

Stereoselective formal synthesis of (+)-allokainic acid was accomplished starting from L-glutamate by using a thiol-mediated acyl radical cyclization as a key step. The cyclization of a formylalkenoate proceeded in a highly diastereoselective manner to give trans-4,5-disubstituted pyrrolidin-3-one without the production of the cis-isomer. The pyrrolidinone was then converted into the established synthetic intermediate of (+)-allokainic acid via the iron-catalyzed coupling reaction with an isopropenyl Grignard reagent.

Stereoselective radical addition of an acetal to sterically tuned enantiomerically pure N-sulfinyl imines.

Enantiomerically enriched sulfonamides were synthesized by the radical addition of an acetal to enantiomerically pure N-sulfinyl imines using dimethylzinc-air and boron trifluoride diethyl etherate. Higher levels of stereocontrol were observed by using a mesitylenesulfinyl group. Furthermore, an amine and an amino alcohol with high enantiomeric purity were obtainable from the sulfonamide product.

Chiral amidophosphane-rhodium(i)-catalyzed asymmetric conjugate arylation of acyclic enones with arylboronic acids.

A catalytic asymmetric conjugate arylation of acyclic alpha,beta-unsaturated ketones with arylboronic acids was catalyzed by 3 mol% of chiral amidomonophosphane 1-rhodium(I) in the presence of potassium hydroxide in a mixture of 1,4-dioxane and water at 70 degrees C to afford 1,4-conjugate arylated acyclic ketones with high enantiomeric excess in high chemical yield. Thirteen examples of the reaction demonstrate the general applicability of the catalytic system.

Steric tuning of the amidomonophosphane-rhodium(I) catalyst in asymmetric addition of arylboroxines to N-phosphinoyl aldimines.

Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-phosphinoylaldimines was realized by the steric tuning of a diphenylphosphorus moiety to a di(o-tolyl)phosphorus moiety of a chiral amidomonophosphane. The presence of MS 4 A in a 5:1 solvent mixture of dioxane-propanol was essential to afford the corresponding diarylmethylamines in high yield.