An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles from common chiral aziridines

An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles was successfully achieved via Pd-catalyzed intramolecular C-N bond formation between the nitrogen originated from the aziridine and the halogen containing aromatic carbon. This reaction has a broad substrate scope to provide various enantiomerically pure (3,4-dihydro-2H-benzo[b][1,4]oxazin-3-yl)methanols, 2-hydroxymethyl-1,2,3,4-tetrahydroquinolines and (1,2,3,4-tetrahydroquinoxalin-2-yl)methanols from common chiral aziridines in good yields.     

Efficient synthesis of cis-thiazolidinethiones derived from ephedrines

The reaction of chlorodeoxypseudoephedrine or chlorodeoxynorpseudoephedrine hydrochlorides with sodium dithiocarbonate in stirring ethanol at 0 °C to stereoselectively afford the corresponding cis-thiazolidinethiones in good yields (81% and 95%) is reported. The in situ formation of a cis-aziridine to explain the presence of trans-thiazolidinethione as a side product is proposed when the same reaction was carried out at room temperature. In addition, a 70:30 mixture of trans-isomers of a thiazolidinethione/isothiazolidinethione was formed when a cis-aziridine NH was reacted with carbon disulfide in refluxing ethanol. The analogous reaction with cis-aziridine N-Me stereoselectively affords the corresponding cis-thiazolidinethione. The ¹H and ¹³C NMR data of the thiazolidinethiones were assigned. cis-3,4-Dimethyl-5-phenylthiazolidine-2-thione was crystallized from ethanol and its X-ray diffraction structure was analyzed.     

An efficient and selective synthesis of 2,5-substituted pyrroles by gold-catalysed ring expansion of alkynyl aziridines

A range of substituted alkynyl aziridines undergo a ring expansion to afford 2,5-substituted pyrroles under gold catalysis. While effective conditions can be generated from other gold sources, a combination of Ph₃PAuCl and AgOTs generate a catalyst system that provides extremely clean cycloisomerisation reactions requiring minimal work-up and purification.     

Direct synthesis of chiral aziridines from N-tert-butyl-sulfinylketimines

The direct preparation of a range of variously substituted chiral tert-butylsulfinylketimines was achieved in good yield (41-90%), with relatively rapid reaction times (4-15 hours); their synthetic application was examined through the reaction with the ylides derived from trimethylsulfonium iodide and S-allyl tetrahydrothiophenium bromide, affording convenient access to a diverse range of highly substituted chiral aziridines in up to 78% yield and > 90% d.e.     

Addition reactions of iodomethyllithium to imines. A direct and efficient synthesis of aziridines and enantiopure amino aziridines

An efficient and general synthesis of aziridines by the reaction of imines derived from p-toluenesulfonamides with in situ generated iodomethyllithium, with a simple and rapid experimental protocol, is reported for the first time. The reaction with the chiral aldimine derived from phenylalaninal allowed access to (2R,1'S)-2-(1'-aminoalkyl)aziridine with very high diastereoselectivity, in enantiopure form. A mechanism to explain this novel reaction is proposed.     

An efficient synthesis of enamides from ketones

A new synthesis of enamides from ketones is disclosed that involves a phosphine-mediated reductive acylation of oximes. The resulting enamides are isolated in good yields (up to 89%) and excellent purity, permitting a subsequent hydrogenation to access enantiopure acetamides at catalyst loadings practical for large-scale applications.     

Asymmetric synthesis of 1-deoxyazasugars from chiral aziridines

A general and facile synthesis of enantiopure 1-deoxyazasugars was achieved from stereoselective dihydroxylation of a common synthetic intermediate, piperidine ring fused oxazolidin-2-one, originating from a commercially available starting substrate, chiral aziridine-2-carboxylate, in high yields.     

An efficient synthesis of (+)-decursinol from umbelliferone

An efficient, practical and enantioselective total synthesis of (+)-decursinol, which has diverse range of biological properties including anti-cancer, anti-Helicobacter pylori, and strong antinociceptive activities, has been achieved in five steps with 41.4% overall yield from umbelliferone. The improved ring construction from coumarin to linear pyranocoumarin has been obtained through quinonemethide intermediate by using phenylboronic acid with propionic acid.     

An efficient synthesis of synargentolide A from d-mannitol

An efficient synthesis of synargentolide A is described by using d-mannitol and d-malic acid. The key features of the synthetic strategy include Wittig olefination, ring closing-metathesis reaction and cross-metathesis reaction for the formation of synargentolide A.     

An efficient synthesis of isocarbacyclin starting from furfural

Two synthetic routes to isocarbacyclin starting from furfural are described. One route involves the regioselective hydrogenation of the disubstituted olefin in the presence of two other olefinic double bonds, and the other includes the highly regioselective organocopper coupling with the allylic etectrophile as a key step.     

An efficient synthesis of pyrimidines from beta-amino alcohols

[reaction: see text] Pyrimidinones 3 were chemoselectively reduced by using metal-catalyzed hydrogenation and stereoselectively substituted by various nucleophiles. Starting from beta-amino alcohols 1, the overall process allows efficient access to substituted pyrimidines 4 and 6.     

A convenient and efficient ring-opening reaction of aziridines with acetylenes and synthesis of dihydropyrroles

In the presence of ^tBuOK, reaction of acetylenes with N-Ts substituted aziridines derived from both cyclic and acyclic alkenes at room temperature gave rise to homopropargylamines in good to high yields and in high regioselectivity. Not only Ph- and Me₃Si-substituted acetylenes but also acetylene itself was suitable reagents. Treatment of ring-opening products with I₂ and AgOAc in the presence of K₂CO₃ provided dihydropyrroles in high yields. One-pot synthesis of dihydropyrroles was also realized by the reaction of aziridines and phenylacetylene in the presence of NaH followed by the treatment with I₂ and AgOAc.     

Novel stereoselective synthesis of functionalized oxazolidinones from chiral aziridines

Enantiomerically pure N-(R)-alpha-methylbenzyl-4(R)-(chloromethyl)oxazolidinones (4R)-5a-k were synthesized in one step and high yields from various aziridine-2-methanols (S)-2a-k by intramolecular cyclization with phosgene. The alpha-methylbenzyl substituent on the nitrogen was easily cleaved to give both enanatiomers of 4-(chloromethyl)oxazolidinones (R)-7a and (S)-7a. (R)-7a was used for the efficient syntheses of (L)-homophenylalaninol analogues (S)-12a-j. We also applied the same methodology to prepare oxazolidinones 9a-c containing a heteroatom-substituted alkyl group at C-4 in high yields.     

Phosphite-mediated annulation: an efficient protocol for the synthesis of multi-substituted cyclopropanes and aziridines

In the presence of phosphite or phosphine, the reaction between 4-, 2-nitrobenzaldehyde and methylidenemalononitriles proceeded smoothly to give the cyclopropane derivatives in high yields, while the reaction between 4-, 2-benzaldehyde, and N-tosylbenzaldimines afforded the azidridine derivatives in moderate to high yields. A plausible mechanism was proposed and the strongly electron-withdrawing nitro-group is believed to play a critical role in these transformations.     

An efficient synthesis of vinylogous carbamates from alkyl azides

An efficient one-pot synthesis of vinylogous carbamates is reported starting from alkyl azides by using NH₄Cl/Zn dust.     

An efficient one-pot synthesis of nitriles from acid chlorides

Treatment of aliphatic, aromatic as well as heterocyclic acid chlorides with sulfonamide in sulfolane at 120°C for 3 hours produces the corresponding nitriles in high yields.