Michel Gravel

NHC-catalyzed ring expansion of oxacycloalkane-2-carboxaldehydes: a versatile synthesis of lactones.

Imidazolinium-derived carbenes catalyze the ring-expansion lactonization of oxacycloalkane-2-carboxaldehydes. A variety of functionalized five-, six-, and seven-membered lactones can be formed efficiently under mild reaction conditions. The success of this new method for the construction of lactones is highly influenced by the electronic nature of the carbene catalyst.

N,N‐Diethanolaminomethyl Polystyrene: An Efficient Solid Support to Immobilize Boronic Acids

The key to the efficiency of N,N-diethanolaminomethyl polystyrene (DEAM-PS), the first solid support capable of coupling to boronic acids, is the formation of a stable, resin-bound boronic ester ate adduct (see scheme). With this resin it is now possible to efficiently immobilize a wide variety of boronic acids including functionalized ones that can be derivatized by solid-phase combinatorial synthesis.

NHC-catalyzed spiro bis-indane formation via domino Stetter-aldol-Michael and Stetter-aldol-aldol reactions.

Two novel domino NHC-catalyzed spirocyclizations are described herein, enabling the rapid construction of three new carbon-carbon bonds and a quaternary center with high diastereoselectivity. A variety of spiro bis-indane structures are assembled in a single step from simple o-phthaldialdehyde derivatives.

Highly Enantioselective Intermolecular Stetter Reactions of β-Aryl Acceptors: α-Ketoester Moiety as Handle for Activation and Synthetic Manipulations

The use of β,γ-unsaturated-α-ketoesters in the intermolecular Stetter reaction furnishes 1,2,5-tricarbonyl compounds in high yield and excellent enantioselectivity. The α,δ-diketoesters generated using this methodology serve as useful synthetic building blocks via chemo- and diastereoselective transformations.

2,6-Bis[(2S)-tetrahydrofuran-2-yl]phenyl diselenide: An effective reagent for asymmetric electrophilic addition reactions to olefins

Abstract The enantioselective synthesis of a new and extremely effective organoselenium reagent ( 2 ) is reported. This chiral reagent was found to react with alkenes with a very high degree of facial selectivity in selenomethoxylation and ring closure reactions. In some cases the diastereoselectivities were found to be as high as 98%.

NHC-Catalyzed Intramolecular Redox Amidation for the Synthesis of Functionalized Lactams

A very efficient NHC-catalyzed lactamization reaction is reported. For most cases, the ring expansion reaction proceeds to cleanly furnish five- and six-membered N-Ts and N-Bn lactams, without the need for further purification. Evidence is presented suggesting a dual role for the stoichiometric base: (1) deprotonation of the triazolium precatalyst and (2) activation of the nitrogen leaving group through hydrogen bonding.

Chemoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions: Importance of the Fused Ring in Triazolium Salts

Morpholinone- and piperidinone-derived triazolium salts are shown to catalyze highly chemoselective cross-benzoin reactions between aliphatic and aromatic aldehydes. The reaction scope includes ortho-, meta-, and para-substituted benzaldehyde derivatives with a range of electron-donating and -withdrawing groups as well as branched and unbranched aliphatic aldehydes. Catalytic loadings as low as 5 mol % give excellent yields in these reactions (up to 99%).

Highly chemo- and enantioselective cross-benzoin reaction of aliphatic aldehydes and α-ketoesters.

An electron-deficient, valine-derived triazolium salt is shown to catalyze a highly chemo- and enantioselective cross-benzoin reaction between aliphatic aldehydes and α-ketoesters. This methodology represents the first high yielding and highly enantioselective intermolecular cross-benzoin reaction using an organocatalyst (up to 94% ee). Further diastereoselective reduction of the products gives access to densely oxygenated compounds with high chemo- and diastereoselectivity.

Diastereoselective Synthesis of Indanes via a Domino Stetter−Michael Reaction

N-Heterocyclic carbenes were found to catalyze a domino Stetter-Michael reaction for the synthesis of indanes. The products were obtained in good yield and diastereomeric ratio, allowing access to highly functionalized indanes under mild conditions. In addition, the functional groups present on the indanes could be used for the synthesis of polycyclic pyrroles.

Origin of Chemoselectivity in N-Heterocyclic Carbene Catalyzed Cross-Benzoin Reactions: DFT and Experimental Insights

An exploration into the origin of chemoselectivity in the NHC-catalyzed cross-benzoin reaction reveals several key factors governing the preferred pathway. In the first computational study to explore the cross-benzoin reaction, a piperidinone-derived triazolium catalyst produces kinetically controlled chemoselectivity. This is supported by (1)H NMR studies as well as a series of crossover experiments. Major contributors include the rapid and preferential formation of an NHC adduct with alkyl aldehydes, a rate-limiting carbon-carbon bond formation step benefiting from a stabilizing π-stacking/π-cation interaction, and steric penalties paid by competing pathways. The energy profile for the analogous pyrrolidinone-derived catalyst was found to be remarkably similar, despite experimental data showing that it is less chemoselective. The chemoselectivity could not be improved through kinetic control; however, equilibrating conditions show substantial preference for the same cross-benzoin product kinetically favored by the piperidinone-derived catalyst.