Phase-Transfer Catalysis via a Proton Sponge: A Bifunctional Role for Biscyclopropenimine

The use of a bis­(diisopropylamino)­cyclopropenimine-substituted bis-protonated proton sponge as a bifunctional phase-transfer catalyst is reported. Experimental studies and DFT calculations suggest it operates simultaneously as a hydrogen bond donor and a phase-transfer catalyst, facilitating the movement of charged intermediates from the interface to the organic phase via favorable partitioning of hydrophilic/hydrophobic surface areas, resulting in high catalytic activity

Synthesis, Theoretical Analysis, and Experimental p<i>K</i>_a Determination of a Fluorescent, Nonsymmetric, In–Out Proton Sponge

Herein, we report the synthesis and theoretical investigation of a nonsymmetric bis­(diisopropylamino)­cyclopropenimine (DAC)-functionalized proton sponge derivative, coined the “Janus” sponge. The reported sponge was isolated as a monoprotonated salt, though no intramolecular hydrogen bond was observed. Homodesmotic equations supported the absence of a N–HN intramolecular hydrogen bond and a relatively low freebase strain, while DFT calculations and X-ray crystallography revealed the presence of a hydrogen bond to the Cl^– counterion. Associated with this fact was the rare in–out geometry of the basic nitrogens, which represents the first such instance in a proton sponge not having an <i>ortho</i>-substituent and/or being in a protonated state. Furthermore, N_LP donation into the cyclopropenium cation was found to stabilize this unprecedented in–out geometry. The measured p<i>K</i>_a was determined to be 23.8, in good agreement with the computed value of 23.9. Lastly, the Janus sponge was found to have fluorescent properties both in the solid state and in solution, which notably represents the first example of a cyclopropenimine-based fluorescent organic compound

A Mechanistic Model for the Aziridine Aldehyde-Driven Macrocyclization of Peptides

Aziridine aldehyde-driven macrocyclization of peptides is a powerful tool for the construction of biologically active macrocycles. While this process has been used to generate diverse collections of cyclic molecules, its mechanistic underpinnings have remained unclear. To enable progress in this area we have carried out a mechanistic study, which suggests that the cyclization owes its efficiency to a combination of electrostatic attraction between the termini of a nitrilium ion intermediate and intramolecular hydrogen bonding. Our model adequately explains the experimentally observed trends, including diastereoselectivity, and should facilitate the development of other macrocyclization reactions

Fluorescence of Cyclopropenium Ion Derivatives

The synthesis of cyclopropenium-substituted amino compounds and analysis of their photophysical properties is described. Systematic structural modifications of these derivatives lead to measurable and predictable changes in molar extinction coefficients, quantum yields, and Stokes shifts. Using time-dependent density functional theory (TD-DFT) calculations, the origin of these trends was traced to internal charge transfer (ICT) coupled with ensuing structural reorganization for select naphthalene functionalized derivatives. Associated with this structural reorganization was an inward gearing of the cyclopropenium ring and twisting of the <i>peri</i>-NMe₂ group into coplanarity with the naphthalene ring system. Further, reinforcement of an intramolecular H-bond (IMHB) in the excited state of these derivatives alludes to the importance of photoinduced H-bonding in this new class of cyclopropenium based fluorophores

Shifting the Energy Landscape of Multicomponent Reactions Using Aziridine Aldehyde Dimers: A Mechanistic Study

A multicomponent reaction between an aziridine aldehyde dimer, isocyanide, and l-proline to afford a chiral piperazinone was studied to gain insight into the stereodetermining and rate-limiting steps of the reaction. The stereochemistry of the reaction was found to be determined by isocyanide addition, while the rate-limiting step was found to deviate from traditional isocyanide-based multicomponent reactions. A first-order rate dependence on aziridine aldehyde dimer and a zero-order rate dependence on all other reagents have been obtained. Computations at the MPWPW91/6-31G­(d) level supported the experimental kinetic results and provide insight into the overall mechanism and the factors contributing to stereochemical induction. These factors are similar to traditional isocyanide-based multicomponent reactions, such as the Ugi reaction. The computations revealed that selective formation of a <i>Z</i>-iminium ion plays a key role in controlling the stereoselectivity of isocyanide addition, and the carboxylate group of l-proline mediates stereofacial addition. These conclusions are expected to be applicable to a wide range of reported stereoselective Ugi reactions and provide a basis for understanding the related macrocyclization of peptides with aziridine aldehydes

Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines

We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]­heptanes from naturally occurring <i>trans</i>-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities. These two diastereoisomeric phosphines functioned as pseudoenantiomers, providing their chiral pyrrolines with opposite absolute configurations

Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines

We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]­heptanes from naturally occurring <i>trans</i>-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities. These two diastereoisomeric phosphines functioned as pseudoenantiomers, providing their chiral pyrrolines with opposite absolute configurations

Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines

We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]­heptanes from naturally occurring <i>trans</i>-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities. These two diastereoisomeric phosphines functioned as pseudoenantiomers, providing their chiral pyrrolines with opposite absolute configurations

Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines

We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]­heptanes from naturally occurring <i>trans</i>-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities. These two diastereoisomeric phosphines functioned as pseudoenantiomers, providing their chiral pyrrolines with opposite absolute configurations