Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkyne

Asymmetric Transfer Hydrogenation of Heterocyclic Compounds in Continuous Flow Using an Immobilized Chiral Phosphoric Acid as the Catalyst

This manuscript describes transfer hydrogenation of bicyclic nitrogen containing heterocyclic compounds using immobilized chiral phosphoric acid (R)-PS-AdTRIP catalyst 3a in batch and continuous flow. It was discovered that significant improvement in enantioselectivities was achieved in continuous flow with a fluidized bed reactor packed with (R)-PS-AdTRIP when the flow rate was increased from 0.2 mL/min to 2.0-2.5 mL/min. The optimized continuous flow conditions consistently provided 4-6% ee higher selectivity than transfer hydrogenation in batch with 2 mol% of (R)-PS-AdTRIP (3a) and were used to generate multiple chiral products with the same fluidized bed reactor

Enantioselective Parallel Kinetic Resolution of Aziridine-Containing Quinoxalines via Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation

This manuscript describes asymmetric synthesis of novel chiral aziridinoquinoxaline scaffolds using chiral phosphor-ic acid-catalyzed parallel kinetic and kinetic resolutions under transfer hydrogenation conditions with Hantzsch es-ters. While the achiral phosphoric acids such as BPPA were found to promote diastereoselective substrate-controlled reductions from the more sterically accessible face with excellent diastereoselectivities, (R)-TRIP catalyst was unique in dictating the catalyst-controlled Si-face selectivity for both enantiomers of the starting materials. The parallel kinet-ic resolution was successfully accomplished for 16 different substrates and led to highly enantioenriched and readily separable diasteromers with (S)-configuration of the newly formed stereocenter (32-61% yield, 64-99% ee, for the (S,S,R)-diastereomers and 7-45% yield, 97-99% ee for the (R,R,S)-diastereomers). This process could be coupled with ring-opening of the (S,S,R)-diastereomer with thiophenol to produce chiral tetrahydroquinoxalines with three con-tiguous stereocenters

Synthesis of 1- (3- (1- substituted- 1,2,3- triazol- 4- yl)- 1,2,4- triazol- 5- yl)- tetrazoles by Sequential Assembly of Azole Fragments

Only few efficient methods for the preparation of polyazoles containing three or four nitrogen atoms in each azole cycle exist. We have developed a novel synthetic strategy that allows the sequential assembly of 1,2,3- triazole, 1,2,4- triazole, and tetrazole fragments into a new stable polyazole. Along the novel strategy, some known procedures have been optimized to achieve better conversion, selectivity, and, in general, overall efficiency.In this study, we report the Azole- Assembly Alignment (A3): a concise three step ring- forming synthesis ligates 1,2,3- triazole, 1,2,4- triazole and tetrazole to selectively give polydentate nitrogen rich ligand systems. Full analysis data of intermediates and final compounds, optimization studies and improvements of known synthetic methods are included.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171185/1/slct202102459_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171185/2/slct202102459-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171185/3/slct202102459.pd

Studies of Catalyst-Controlled Regioselective Acetalization and Its Application to Single-Pot Synthesis of Differentially Protected Saccharides.

This article describes the studies on regioselective acetal protection of monosaccharide-based diols using chiral phos-phoric acids (CPAs) and their immobilized polymeric variants, (R)-Ad-TRIP-PS and (S)-SPINOL-PS as the catalysts. These catalyst-controlled regioselective acetalizations were found to proceed with high regioselectivities (up to >25:1 rr) on various D-glucose, D-galactose, D-mannose and L-fucose derived 1,2-diols, and could be carried in a re-giodivergent fashion depending on the choice of the chiral catalyst. The polymeric catalysts were conveniently recy-cled and reused multiple times for gram scale functionalizations with catalytic loading as low as 0.1 mol%, and their performance was often found to be superior to the performance of their monomeric variants. These regioselective CPA-catalyzed acetalizations were successfully combined with common hydroxyl group functionalizations as single-pot telescoped procedures to produce 34 regioisomerically pure differentially protected mono- and disaccharide de-rivatives. To further demonstrate the utility of the polymeric catalysts, the same batch of (R)-Ad-TRIP-PS catalyst was recycled and reused to accomplish single-pot gram-scale syntheses of 6 differentially protected D-glucose derivatives. The subsequent exploration of the reaction mechanism using NMR studies of deuterated and nondeuterated sub-strates revealed that low-temperature acetalizations happen via syn-addition mechanism, and that the reaction regi-oselectivity exhibits strong dependence on the temperature. The computational studies indicate complex tempera-ture-dependent interplay of two reaction mechanisms, one involving an anomeric phosphate intermediate and an-other via concerted asynchronous formation of acetal that results in syn-addition products. The computational models also explain the steric factors responsible for the observed C2-selectivities and are consistent with experimentally observed selectivity trends