Research

The asymmetric electrophilic amination of allylic boronates is realized using a chiral diol as a catalyst. This simple catalyst promotes the transfer of the allylic pendant to the activated N=N double bond of azodicarboxylate, leading to a series of enantioenriched hydrazides. The key aspect of the reaction mechanism is the ability of the chiral diol to form a chiral boronic ester that is more reactive than the achiral precursor, suppressing the racemic background reaction in favor of the enantioselective pathway. The reaction conditions ensure a rapid catalyst turnover, thus overcoming the typical rate-limiting step observed in previous allyl transfer reactions of boronic esters.

• Chiral diol catalyses the asymmetric ally-transfer reaction of crotyl boronates to azodicarboxylates generating new chiral hydrazides.

The first enantioselective and diastereoselective synthesis of atropisomeric hydrazides was performed using one-pot sequential catalysis based on the enamine amination of branched aldehydes followed by phase-transfer N-alkylation. Chiral hydrazides were obtained with high yields and stereocontrol using commercially available reagents and catalysts. The permutation of catalysts allowed for a stereodivergent approach to a new class of atropisomers.

• Synthesis of Atropisomeric Hydrazidesby One-Pot Sequential Enantio-and Diastereoselective Catalysis

The organocatalytic axially enantioselective Knoevenagel condensation between prochiral cyclohexanones and oxindoles is presented. The reaction, promoted by a primary amine, proceeded smoothly and furnished unprecedented examples of novel cyclohexylidene oxindoles displaying axial chirality.

• Knoevenagel Reaction applied to the synthesis of alkylidene-oxindoles atropisomers

Mechanistic studies clarifying how chiral primary amines control the stereochemistry of vinylogous processes are rare. We report a density functional theory (DFT) computational study for the comprehension of the reaction mechanism of the vinylogous atroposelective desymmetrization of N-(2-t-butylaryl)maleimide catalyzed by 9-amino(9-deoxy)epi-quinine. Our results illustrate how the origin of the atroposelectivity was realized by the catalyst through steric and dispersion interactions. The role of N-Boc-l-Ph-glycine was crucial for the formation of a closed transition-state geometry and the activation of both reaction partners.

• Computational Investigation on the Origin of Atroposelectivity for the Cinchona Alkaloid Primary Amine-Catalyzed Vinylogous Desymmetrization of N‑(2‑t‑Butylphenyl)maleimides

The atroposelective desymmetrization of N-arylmaleimides was realized by means of a primary amine catalyzed Diels–Alder reaction of enones. The chiral axis as new element of chirality is generated under the remote control of the catalyst that selectively drives the formal Diels–Alder reaction through an exclusive stereochemical outcome.

• Organocatalytic Atroposelective Formal Diels–Alder Desymmetrization of N-Arylmaleimides

Remote control of the axial chirality of N-(2-t-butylphenyl)succinimides was realized via the vinylogous Michael addition of 3-substituted cyclohexenones to N-(2-t-butylphenyl)maleimides. 9-Amino(9-deoxy)epi-quinine promoted the enantioselective desymmetrization, leading to atropisomeric succinimides with two adjacent stereocenters.

• Vinylogous reactivity applied to the synthesis of atropisomers