Stereoselective cycloadditions of chiral acyl-nitroso compounds; selective reactions of ring-cleaved cycloadducts leading to a new approach to polyoxamic acid

Diesters obtained from diacids produced by oxidative ring cleavage of cycloadducts derived from acyl-nitroso compounds and cyclic 1,3-dienes undergo highly regioselective hydrolysis on reaction with lithium hydroperoxide, which allows for easy differentiation of the carboxyl groups leading to a new approach to polyoxamic acid.     

An expeditious formal synthesis of (−)-epibatidine

A short route to (−)-epibatidine is described. It includes a hetero-Diels–Alder reaction of a chiral non-racemic acyl-nitroso derivative and 2-t-butyldimethylsilyloxycyclohexadiene followed by chemical manipulations to furnish a known precursor of the natural product in 11% overall yield.     

Ab initio Study of Mechanism of Forming Germanic Bis-Heterocyclic Compound Between Dichloro-Germylene Carbene (Cl2Ge=C:) and Formaldehyde

The mechanism of the cycloaddition reaction of forming germanic bis-heterocyclic compound between singlet dichloro-germylene carbene and formaldehyde has been investigated with CCSD(T)//MP2/6-31G^* method, from the potential energy profile, we predict that the re-action has two competitive dominant reaction pathways. The presented rule of this reaction: the 2p unoccupied orbital of the C atom in dichloro-germylene carbene insert the π orbital of formaldehyde from oxygen side, resulting in the formation of intermediate. In the interme-diate and between two reactants, because of the two bonding π orbital in dichloro-germylene carbene and formaldehyde have occurred [2+2] cycloaddition reaction, forming two four-membered ring compounds in which Ge and O are in the opposite orientation and in the syn-position, respectively. Because of the unsaturated property of C atom from carbene in the two four-membered ring compounds, they further reacts with formaldehyde, resulting in the generation of two germanic bis-heterocyclic compounds.     

"Click" saccharide/beta-lactam hybrids for lectin inhibition

Hybrid glycopeptide beta-lactam mimetics designed to bind lectins or carbohydrate recognition domains in selectins have been prepared according to a "shape-modulating linker" design. This approach was implemented using the azide-alkyne "click" cycloaddition reaction, and as shown by NMR/MD experiments, binding of the resulting mimetics to Ulex Europaeus Lectin-1 (UEL-1) occurred after a "bent-to-extended" conformational change around a partially rotatable triazolylmethylene moiety.     

Cycloaddition of trifluoromethyl azafulvenium methides: synthesis of new trifluoromethylpyrrole-annulated derivatives

The chemistry of trifluoromethyl azafulvenium methides was explored leading to a new route to trifluoromethylpyrrole-annulated systems. The first evidence of azafulvenium methides acting as 1,3-dipoles is reported. These azafulvenium methides showed site selectivity in the reaction with strong electron-deficient dipolarophiles leading exclusively to 1,3-cycloadducts. In the cycloaddition with less-activated dipolarophiles 1,7-cycloadducts resulting from [8π+2π] cycloaddition are also formed. FMO analysis of the cycloaddition reactions allowed the rationalization of the observed selectivity.     

Cascade cyclization, dipolar cycloaddition of azomethine imines for the synthesis of pyrazolidines

A tandem multi-step, one-pot reaction of aldehydes with hydrazines has been used for the preparation of tetrahydropyrazoles and dihydropyrazoles. The chemistry involves condensation then cyclization, followed by inter- or intramolecular dipolar cycloaddition of the resulting azomethine imine intermediates. The intramolecular cycloaddition gives fused tricyclic compounds as single diastereoisomers. The intermolecular cycloaddition was successful with a variety of activated alkene and alkyne dipolarophiles.     

Copper(II)-catalyzed room temperature aerobic oxidation of hydroxamic acids and hydrazides to acyl-nitroso and azo intermediates, and their Diels-Alder trapping

CuCl(2), in the presence of a 2-ethyl-2-oxazoline ligand, is an effective catalyst for the room temperature, aerobic oxidation of hydroxamic acids and hydrazides, to acyl-nitroso and azo dienophiles respectively, which are efficiently trapped in situ via both inter- and intramolecular hetero-Diels-Alder reactions with dienes. Both inter- and intramolecular variants of the Diels-Alder reaction are suitable under the reaction conditions using a variety of solvents. Under the same conditions, an acyl hydrazide was also oxidized to give an acyl-azo dienophile which was trapped intramolecularly by a diene.     

Design and synthesis of 1,2,3-triazole-fused chiral medium-ring benzo-heterocycles, scaffolds mimicking benzolactams

Based on "amide-triazole bioequivalence" principle, 1,2,3-triazole-fused chiral medium ring benzo-heterocycles capable of mimicking benzolactams were designed. Their syntheses were accomplished by cycloaddition of different sugar-derived azidoalkynes. While triazole-fused eight-membered benzo-heterocycles were formed by exclusive intramolecuclar [3 + 2] cycloaddition, attempted preparation of seven-membered analogues led to some intermolecular cycloaddition resulting in a dimeric macrocyclic product, in addition to intramolecular cycloaddition furnishing the expected heterocycle.     

Solid-phase synthesis of oxazolidinones by cycloaddition of resin-bound epoxides with isocyanates

The first solid-phase synthesis of oxazolidinones by cycloaddition of resin-bound epoxides with isocyanates is described. Synthesis of the title compounds was achieved by alkylation of resin-bound carbamates with glycidyl tosylate, followed by cycloaddition of the resulting epoxides with isocyanates at elevated temperature in high yields and purity. Because N-aryloxazolidinones have been known to possess various biological activities, this method is useful from the viewpoint of drug discovery.     

Synthesis of δ-thiolactams by the aza-Diels-Alder reaction of in situ generated allenyltrimethylsilylthioketenes with imines

Allenyltrimethylsilylthioketenes, generated in situ through [3,3] sigmatropic rearrangement of trimethylsilylethynyl propargyl sulfides, underwent facile [4+2] cycloaddition with imines to afford the corresponding δ-thiolactams. The resulting 2-trimethylsilyl-4-methylenetetrahydroquinolidine-2-thione, obtained by the [4+2] cycloaddition using piperideine as a dienophile, was transformed into (±)-lupinine in six steps.     

Synthesis of multiply functionalized benzenes via ruthenium-catalyzed cycloaddition of diiododiynes

Highly functionalized benzenes were precisely synthesized via multi-step processes consisting of ruthenium-catalyzed [2+2+2] cycloaddition of diiododiynes with an ethynylboronate or terminal alkynes, and subsequent chemo- and regio-selective palladium-catalyzed C-C bond-forming reactions of the resulting cycloadducts. The sequential cycloaddition/coupling process was applied to the synthesis of oligo(p-phenylene ethynylene)s.     

Oxidation of Enones for Regioselective [3+2] Cycloaddition through γ-Enone Radical Intermediates

Herein, an oxidization reaction of enones with a Cu^II complex that leads to a new type of regioselective [3+2] cycloaddition is reported. Highly functionalized cyclopentenes and spirocyclic compounds are obtained in moderate-to-good yields. This cycloaddition reaction occurred through the formation of γ-enone radicals, providing a rarely explored reactivity pattern for enones.     

3 + 2] cycloaddition reactions of 4-alkyl-3-hydroxy-2H-pyrazolo[4,3-c]isoquinolinium inner salts

Heating dipolarophiles with 4-alkyl-3-hydroxy-2H-pyrazolo[4,3-c]isoquinolinium hydroxide inner salts results in [3 + 2] cycloaddition across positions 3a and 5 of the aromatic system to give the [3 + 2] cycloadducts in good yield. When the 4-alkyl substituent is a 2-acetate ester and the methylene group can be deprotonated, a second mode of [3 + 2] cycloaddition becomes available for the resulting anion (across the side chain methine group and position 5 of the aromatic system) and occurs under basic conditions, allowing either of two modes of [3 + 2] cycloaddition to be selected by appropriate choice of reaction conditions.     

Highly Enantioselective [3+2] Cycloaddition of Vinylcyclopropane with Nitroalkenes Catalyzed by Palladium(0) with a Chiral Bis(tert‐amine) Ligand

An enantioselective [3+2] cycloaddition of vinyl cyclopropane derived from 1,3‐indanedione with nitroalkenes catalyzed by palladium(0) with a chiral bis(tert‐amine) ligand was developed in high yields with good diastereoselectivities and excellent enantioselectivities. The resulting bis(tert‐amine)–palladium complex proved to be a highly efficient catalyst for this cycloaddition.     

Cycloaddition to a C3-ethynylated chlorophyll derivative and self-aggregation of zinc chlorin–pyrazole/triazole conjugates

Several kinds of cycloaddition reactions were applied to C3-ethynylated pyropheophorbide-a methyl ester to develop C3-functionalized chlorophyll derivatives. Its [2+2] cycloaddition with tetracyanoethylene, [2+3] cycloaddition with diazomethane, [2+3] Huisgen reaction with trimethylsilyl azide, and [2+4] Diels–Alder reaction with tetraphenylcyclopentadienone gave the expected products in moderate to high yields. Zinc complex of the resulting 3-pyrazolyl-chlorin was found to show self-aggregation in a less polar solvent, in an aqueous micelle, and in the solid thin films more readily than the corresponding zinc 3-triazolyl-chlorin.     

Diastereoselective synthesis of novel iminosugar-containing UDP-Galf mimics: potential inhibitors of UDP-Gal mutase and UDP-Galf transferases

Tetra-O-benzyl-D-glucofuranose was converted into uridine diphosphono-beta-Galf mimics based on an iminosugar skeleton linked to UMP by a 2-hydroxypropyl tether. The synthesis is based on the highly regio- and stereoselective cycloaddition of an original uridin-5'-yl allylphosphonate with a 1,4-dideoxy-1,4-iminogalactitol-derived cyclic nitrone, followed by the reductive elaboration of the cycloaddition product. The resulting iminogalactose-UMP conjugates are novel sugar nucleotide mimics which could be useful as inhibitors of UDP-Gal mutase and UDP-Galf transferases.     

A new method for the synthesis of 2-phenylsulfonylaziridines via the reaction of α-halosulfonyl carbanion to imines

The reaction of lithio α-chloromethyl phenyl sulfone with imines gave aziridines in good yields. The resulting aziridines were alkylated and underwent the 1,3-dipolar cycloaddition with dimethylacetylene dicarboxylate to give pyrroles in excellent yields.     

Photochemical [2 + 2] cycloaddition reactions of 6-alkenyl-3-phenylcyclohex-2-en-1-ones: using biradical conformation control to account for exceptions to the "rule of five"

A series of 6-alkenyl-3-phenylcyclohex-2-enones has been synthesised and the structures of the products obtained from them on irradiation have been determined. The 6-propenyl compounds afforded a tricyclic 'parallel' [2 + 2] cycloaddition product and a bicyclic enone resulting from hydrogen abstraction in the biradical intermediate. The 6-butenyl and 6-pentenyl analogues gave 'crossed' cycloaddition products only. Although the regiochemistry of these cycloaddition reactions cannot be explained in terms of the 'rule of five', it is compatible with the concept of 'biradical conformation control' which is based on a consideration of the energy and structure of the possible 1,4-biradical intermediates.     

Mechanistic studies of hydrazide-catalyzed enantioselective Diels-Alder reactions

The mechanism of the enantioselective, hydrazide-catalyzed Diels-Alder cycloaddition was investigated in detail. Both the formation of the reactive iminium species and the hydrolysis of the product iminium intermediates were found to be extremely rapid, leaving the cycloaddition as the kinetically significant step. Mechanistic studies using NMR showed that a retro-Diels-Alder reaction occurred during the catalytic cycle, suggesting a thermodynamic component to the reaction.     

Gold-catalyzed stereoselective synthesis of azacyclic compounds through a redox/[2 + 2 + 1] cycloaddition cascade of nitroalkyne substrates

We report a new redox/cycloaddition cascade on readily available 1-alkynyl-2-nitrobenzenes that produces complex azacyclic compounds stereoselectively. The core structures of the resulting products are constructed through a formal [2 + 2 + 1] cycloaddition among α-carbonyl carbenoids, nitroso species, and external alkenes.