Electrochemical Vicinal C–H Difunctionalization of Saturated Azaheterocycles

A method to functionalize two vicinal C–H bonds of saturated azaheterocycles is described. The procedure involves subjecting the substrate to a mixture of hydrochloric acid, acetic acid, and acetic anhydride in an undivided electrochemical cell at a constant current, resulting in stereoselective conversion to the corresponding α-acetoxy-β-chloro derivative. The α-position can be readily substituted with a range of other groups, including alkyl, aryl, allyl, alkynyl, alkoxy, or azido functionalities. Furthermore, we demonstrate that the β-chloro position can be engaged in Suzuki cross-coupling. This protocol thus enables the rapid diversification of simple five-, six-, and seven-membered saturated azaheterocycles at two adjacent positions

Higher-Order Cyclopropenimine Superbases: Direct Neutral Brønsted Base Catalyzed Michael Reactions with α‑Aryl Esters

The synthesis and characterization of six new classes of higher-order superbases, including five that incorporate cyclopropenimine functionality, has been achieved. We propose a nomenclature that designates these as the CG₂, GC₂, PC₃, PC₁, C₃, and GP₂ classes of superbases. The p<i>K</i>_BH+ values were measured to be between 29.0 and 35.6 in acetonitrile. Linear correlations of ten superbase basicities vs that of their substituents demonstrated the insulating effect of the cyclopropenimine core. The molecular structures of several of these materials were obtained by single-crystal X-ray analysis, revealing interesting aspects of conformational bias and noncovalent organization. The types of superbasic cores and substituents were each reliably shown to affect selectivity for deprotonation over alkylation. Higher-order cyclopropenimine and guanidine superbase stability to hydrolysis was found to correlate to basicity. Finally, a GC₂ base was found to catalyze conjugate additions of α-aryl ester pronucleophiles, representing the first report of a neutral Brønsted base to catalyze such reactions

Cyclopropenimine-Catalyzed Enantioselective Mannich Reactions of <i>tert</i>-Butyl Glycinates with <i>N</i>‑Boc-Imines

Cyclopropenimine <b>1</b> is shown to catalyze Mannich reactions between glycine imines and <i>N</i>-Boc-aldimines with high levels of enantio- and diastereocontrol. The reactivity of <b>1</b> is shown to be substantially greater than that of a widely used thiourea cinchona alkaloid-derived catalyst. A variety of aryl and aliphatic <i>N</i>-Boc-aldimines are effective substrates for this transformation. A preparative-scale reaction to deliver >90 mmol of product is shown using 1 mol % catalyst. The products of this transformation can be converted into several useful derivatives

Cyclopropenone Catalyzed Substitution of Alcohols with Mesylate Ion

The cyclopropenone catalyzed nucleophilic substitution of alcohols by methanesulfonate ion with inversion of configuration is described. This work provides an alternative to the Mitsunobu reaction that avoids the use of azodicarboxylates and generation of hydrazine and phosphine oxide byproducts. This transformation is shown to be compatible with a range of functionality. A cyclopropenone scavenge strategy is demonstrated to aid purification

Higher-Order Cyclopropenimine Superbases: Direct Neutral Brønsted Base Catalyzed Michael Reactions with α‑Aryl Esters

The synthesis and characterization of six new classes of higher-order superbases, including five that incorporate cyclopropenimine functionality, has been achieved. We propose a nomenclature that designates these as the CG₂, GC₂, PC₃, PC₁, C₃, and GP₂ classes of superbases. The p<i>K</i>_BH+ values were measured to be between 29.0 and 35.6 in acetonitrile. Linear correlations of ten superbase basicities vs that of their substituents demonstrated the insulating effect of the cyclopropenimine core. The molecular structures of several of these materials were obtained by single-crystal X-ray analysis, revealing interesting aspects of conformational bias and noncovalent organization. The types of superbasic cores and substituents were each reliably shown to affect selectivity for deprotonation over alkylation. Higher-order cyclopropenimine and guanidine superbase stability to hydrolysis was found to correlate to basicity. Finally, a GC₂ base was found to catalyze conjugate additions of α-aryl ester pronucleophiles, representing the first report of a neutral Brønsted base to catalyze such reactions

Enantioselective Brønsted Base Catalysis with Chiral Cyclopropenimines

Cyclopropenimines are shown to be a highly effective new class of enantioselective Brønsted base catalysts. A chiral 2,3-bis­(dialkylamino)­cyclopropenimine catalyzes the rapid Michael reaction of a glycine imine substrate with high levels of enantioselectivity. A preparative scale reaction to deliver 25 g of product is demonstrated, and a trivial large scale synthesis of the optimal catalyst is shown. In addition, the basicity of a 2,3-bis­(dialkylamino)­cyclopropenimine is measured for the first time and shown to be approximately equivalent to the P₁-<i>t</i>Bu phosphazene base. An X-ray crystal structure of the protonated catalyst is shown along with a proposed mechanistic and stereochemical rationale

Enantioselective Brønsted Base Catalysis with Chiral Cyclopropenimines

Cyclopropenimines are shown to be a highly effective new class of enantioselective Brønsted base catalysts. A chiral 2,3-bis­(dialkylamino)­cyclopropenimine catalyzes the rapid Michael reaction of a glycine imine substrate with high levels of enantioselectivity. A preparative scale reaction to deliver 25 g of product is demonstrated, and a trivial large scale synthesis of the optimal catalyst is shown. In addition, the basicity of a 2,3-bis­(dialkylamino)­cyclopropenimine is measured for the first time and shown to be approximately equivalent to the P₁-<i>t</i>Bu phosphazene base. An X-ray crystal structure of the protonated catalyst is shown along with a proposed mechanistic and stereochemical rationale

Organocatalytic Carbonyl-Olefin Metathesis

The development of a catalytic carbonyl-olefin metathesis strategy is reported, in the context of the ring-opening metathesis of cyclopropenes with aldehydes using a simple hydrazine catalyst. The key to this reaction is a conceptual blueprint for metathesis chemistry that forgoes the traditional reliance on [2 + 2] cycloaddition modes in favor of a [3 + 2] paradigm

Organocatalytic Carbonyl-Olefin Metathesis

The development of a catalytic carbonyl-olefin metathesis strategy is reported, in the context of the ring-opening metathesis of cyclopropenes with aldehydes using a simple hydrazine catalyst. The key to this reaction is a conceptual blueprint for metathesis chemistry that forgoes the traditional reliance on [2 + 2] cycloaddition modes in favor of a [3 + 2] paradigm

Methods for the Synthesis of Functionalized Pentacarboxycyclopentadienes

Protocols for the synthesis of diverse pentacarboxycyclopentadienes are described. Starting from readily available pentacarbomethoxycyclopentadiene, transesterification offers single-step access to aliphatic ester derivatives, while treatment with amines produces mono- or diamides. For less nucleophilic alcohols, an alternative procedure involving the in situ generation and esterification of a putative cyclopentadiene pentaacid chloride has been developed