Mechanistic Aspects on [3+2] Cycloaddition (32CA) Reactions of Azides to Nitroolefins: A Computational and Kinetic Study.

[3+2] cycloadditions of nitroolefins have emerged as a selective and catalyst-free alternative for the synthesis of 1,2,3-triazoles from azides. We describe mechanistic studies into the cycloaddition/rearomatization reaction sequence. DFT calculations revealed a rate-limiting cycloaddition step proceeding via an asynchronous TS with high kinetic selectivity for the 1,5-triazole. Kinetic studies reveal a second-order rate law, and 13 C kinetic isotopic effects at natural abundance were measured with a significant normal effect at the conjugated olefinic centers of 1.0158 and 1.0216 at the α and ß-carbons of ß-nitrostyrene. Distortion/interaction-activation strain and energy decomposition analyses revealed that the major regioisomeric pathway benefits from an earlier and less-distorted TS, while intermolecular interaction terms dominate the preference for 1,5- over 1,4-cycloadducts. In addition, the major regioisomer also has more favorable electrostatic and dispersion terms. Additionally, while static DFT calculations suggest a concerted but highly asynchronous Ei-type HNO2 elimination mechanism, quasiclassical direct-dynamics calculations reveal the existence of a dynamic intermediate.

Six-Step Syntheses of (-)-1-Deoxyaltronojirimycin and (+)-1-Deoxymannonojirimycin from N-Z-O-TBDPS-l-serinal.

Highly stereoselective six-step syntheses of (-)-1-deoxyaltronojirimycin (altro-DNJ) and (+)-1-deoxymannojirimycin (manno-DNJ) from N-Cbz-O-TBDPS-l-serinal are described. Key transformations involve a two-step preparation of a functionalized dihydropyridin-3-one as a common intermediate followed by Luche reduction and dihydroxylation (for altro-DNJ). The same sequence employing an epoxidation/epoxide opening in place of dihydroxylation furnishes manno-DNJ.

Direct access to tetrasubstituted cyclopentenyl scaffolds through a diastereoselective isocyanide-based multicomponent reaction.

An efficient strategy combining the stereocontrol of organocatalysis with the diversity-generating character of multicomponent reactions is described to produce structurally unique, tetrasubstituted cyclopentenyl frameworks. An asymmetric Michael addition-hemiacetalization between α-cyanoketones and α,ß-unsaturated aliphatic aldehydes was performed for constructing cyclic hemiacetals, which were next employed as chiral bifunctional substrates in a new diastereoselective intramolecular isocyanide-based multicomponent reaction. This approach furnished a diversity of structurally complex compounds - including peptidomimetics and natural product hybrids in high stereoselectivity (up to >99% ee and up to >99 : 1 dr) and in moderate to high yields.

A stereoselective sequential organocascade and multicomponent approach for the preparation of tetrahydropyridines and chimeric derivatives.

A stereoselective multicomponent approach leading to a novel class of pentasubstituted tetrahydropyridines is described. Variation of the components enabled the incorporation of peptide, sugar and steroid moieties to access chimeric derivatives. DFT calculations provide insights about the unprecedented high diastereoselectivity of the MCR.