Pradip K. Maity

Selective One-Pot Synthesis of Allenyl and Alkynyl Esters from β-Ketoesters

A convenient method is described for the dehydration of beta-ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method involves the formation of a vinyl triflate monoanion intermediate that leads to the selective formation of alkynes or allenes depending on additives and conditions used. Product outcomes appear to be a function of unique mono- and dianion mechanisms which are described.

Catalytic synthesis of nonracemic azaproline derivatives by cyclization of β-alkynyl hydrazines under kinetic resolution conditions.

Cyclic addition of a hydrazine nitrogen to unactivated alkynes catalyzed by non-metals. Starting from readily accessible γ-silyl allenyl esters, β-alkynyl hydrazines are prepared in one step and subsequently undergo unprecedented cyclization reactions in the presence of ammonium and phosphonium catalysts leading to dehydro-azaproline products. These heterocycles are also produced in high enantiomeric excesses using chiral ammonium phase transfer catalysts via a kinetic resolution pathway.

Monomer-on-Monomer (MoM) Mitsunobu Reaction: Facile Purification Utilizing Surface-Initiated Sequestration

A monomer-on-monomer (MoM) Mitsunobu reaction utilizing norbornenyl-tagged (Nb-tagged) reagents is reported, whereby purification was rapidly achieved by employing ring-opening metathesis polymerization, which was initiated by any of three methods utilizing Grubbs catalyst: (i) free catalyst in solution, (ii) surface-initiated catalyst-armed silica, or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles.

High-load, hybrid Si-ROMP reagents.

The combination of norbornenyl-tagged (Nb-tagged) silica particles and functionalized Nb-tagged monomers for the generation of hybrid Si-ROMP reagents and scavengers is reported. Specifically Si-ROMP-derived bis-acid chloride, dichlorotriazine, and triphenylphosphine scavenger/reagents have been grafted from the surface of silica particles utilizing surface-initiated, ring-opening metathesis polymerization (ROMP). These hybrid polymeric materials combine the physical properties of current immobilized silica reagents and represent a key advancement in load by merging the inherent tunable properties of the ROMP-derived oligomers with silica supports for application in a parallel synthesis.

Facile (triazolyl)methylation of MACOS-derived benzofused sultams utilizing ROMP-derived OTP reagents.

A combination of MACOS scale-out and ROMP-derived oligomeric triazole phosphates (OTP(n)) have been successfully utilized for the preparation of a 106-member library of triazole containing benzothiaoxazepine-1,1-dioxides. This report demonstrates the utilization of a suite of soluble OTP(n) reagents for facile (triazolyl)methylation of 10 MACOS-derived sultam scaffolds in purification-free process for parallel synthesis of small molecule collections for HTS.

ROMP-derived Oligomeric Phosphates for Application in Facile Benzylation

The development of new ROMP-based oligomeric benzyl phosphates (OBP(n)) is reported for use as soluble, stable benzylating reagents. These oligomeric reagents are readily synthesized from commercially available materials and conveniently polymerized and purified in a one-pot process, affording bench-stable, pure white, free-flowing solids on multigram scale. Utilization in benzylation reactions with a variety of nucleophiles is reported.

Anion Catalyzed Addition of γ-Silylallenyl Esters to Aldehydes: A New Entry into [3.2.1] Bicyclic Natural Products

A significant improvement in the generality and reactivity of MBH-type reactions is made possible by anion catalysis and a 1,3-Brook rearrangement. In this new reaction, both aliphatic and aromatic aldehydes are rapidly added to silylallenes, leading to gamma-carbinol allenoates at low temperatures. The utility of these reaction products is demonstrated by a fast-tracked synthesis of a [3.2.1] bisoxa bicycle that makes up the framework of many biologically active natural products, including vitisinol D, an antithrombotic agent.

Intramolecular monomer-on-monomer (MoM) Mitsunobu cyclization for the synthesis of benzofused thiadiazepine-dioxides.

The utilization of a monomer-on-monomer (MoM) intramolecular Mitsunobu cyclization reaction employing norbornenyl-tagged (Nb-tagged) reagents is reported for the synthesis of benzofused thiadiazepine-dioxides. Facile purification was achieved via ring-opening metathesis (ROM) polymerization initiated by one of three metathesis catalyst methods: (i) free metathesis catalyst, (ii) surface-initiated catalyst-armed silica, or (iii) surface-initiated catalyst-armed Co/C magnetic nanoparticles.

Annulation reactions of allenyl esters: an approach to bicyclic diones and medium-sized rings.

A flexible approach to construct sterically congested bicyclo-alkenedione frameworks is reported. Under the action of potassium carbonate, α-sulphonyl cycloalkanones are added to functionalized allenyl esters, leading to a lactone intermediate that is subsequently reduced to initiate an intramolecular aldol cyclization to [3.2.1], [3.3.1], and [4.3.1] bicycles. Oxidation then affords bicyclic diones in good three-step yields. Under exceptionally mild conditions, these bicycles are converted to highly functionalized medium-sized rings through a Grob-type fragmentation.

Transition Metal, Azide, and Oxidant-Free Homo- and Heterocoupling of Ambiphilic Tosylhydrazones to the Regioselective Triazoles and Pyrazoles

With N-tosylhydrazone as an ambiphilic reagent, an unprecedented cyclization reaction of two identical or different tosylhydrazones has been developed to access various 4,5-disubstituted-2H-triazoles under transition metal, azide, and oxidant-free conditions. A mechanistic rationalization study led to the identification of several electronically diverse unsaturated systems for regioselective synthesis of 1- and 2-substituted 1,2,3-triazoles and pyrazoles.