A highly regioselective [3+2] cycloaddition reaction of nitrones 1 with alkyl 2-aroylcyclopropenecarboxylates generated in situ from alkyl 2-aroyl-1-chlorocyclopropanecarboxylates 2 under basic conditions is described. The reaction proceeded readily to afford ring-fused isoxazolidines 3 in moderate-to-high yields. The strained ring-fused cycloaddition products were selectively transformed into the corresponding polysubstituted pyrroles, for example, pyrrolizine derivatives, through N–O bond cleavage or 1,2-oxazinane derivatives through ring-opening by treatment with HCl·pyridine in alcoholic solvents.

New hexahydrobenzo[b]thiophene derivatives 3 were conveniently synthesized by a fluoride-promoted tandem reaction between cyclic β-thiocyanatoenals 1 and terminal electron-deficient alkenes 2 in low to moderate yield. The reaction was initiated by γ-deprotonation and followed by the Michael addition and nucleophilic attack on sulfur center.

A highly regioselective cascade formal nucleophilic substitution and aldol reaction of 2-aroyl-1-chlorocyclopropanecarboxylic esters with salicylic aldehydes is described. Under basic conditions, 2-aroyl-1-chlorocyclopropanecarboxylic esters are easily converted into cyclopropene intermediates by simple 1,2-elimination of hydrogen chloride. This highly reactive cyclopropene quickly combines with salicylic aldehyde through a regioselective oxa-addition to the strained C=C bond and a subsequent intramolecular aldol reaction to construct C–O and C–C bonds concomitantly and afford tetrahydrocyclopropa[b]chromene derivatives.

Rhodium-catalyzed intramolecular difluoromethylenative dearomatization of phenols to yield azaspirocyclohexadienones containing all-carbon quaternary centers in good to excellent yields was developed. A variety of functional groups proved compatible with the transformation. This method could also be used for difluoromethylenative dearomatization of indoles. Preliminary mechanism studies suggest that a pure radical mechanism is not involved in this reaction.

A two-step sequence to ethyl α-fluorocyclopropanecarboxylates has been developed. Ethyl α-chlorocyclopropanecarboxylates were first obtained through a Michael-initiated ring closure reaction of terminal electron-deficient olefins with ethyl 2,2-dichloroacetate under mild basic conditions. Subsequent smooth conversion into the corresponding monofluorinated analogues in good yields was through a halogen exchange reaction with potassium bifluoride. Further investigation clearly demonstrated that potassium bifluoride in this reaction system played a dual role of base and nucleophilic reagent. This is the first successful example reported hitherto for producing ethyl α-fluorocyclopropanecarboxylate directly through fluorination of its chlorinated analogue with alkali bifluoride.

A highly efficient method for the synthesis of fluorine-containing multisubstituted phenanthridines through Rh-catalyzed alkyne [2+2+2] cycloaddition reactions has been developed. This method exhibits excellent functional-group compatibility. When a bromodifluoromethyl group, rather than a trifluoromethyl group, was employed in the cycloaddition reaction, more-complicated polycyclic compounds were obtained through tandem Rh-catalyzed cycloaddition/CH difluoromethylenation. This route provides convenient access to fluorine-containing polycyclic compounds.

A series of stable chiral C₁-symmetric dinitrogen ligands were conveniently synthesized in high yields by condensation of chiral amines [(–)-exo-bornylamine or (+)-(1S,2S,5R)-menthylamine] with various substituted imidazolecarbaldehydes. With the assistance of base, the ligand L1 in combination with CuCl₂·2H₂O (2.5 mol-% or 5.0 mol-%) can efficiently promote nitroaldol (Henry) reactions between a variety of aldehydes and nitromethane. Both aromatic and aliphatic aldehydes were tolerated in our catalytic system, affording the expected nitroalcohol products in high yields (up to 97 %) and with good enantioselectivities (up to 96 %) under mild reaction conditions.

A cascade Michael–hemiacetalization reaction between β-substituted β-nitroethanols and α,β-unsaturated aldehydes is described, which provides a convenient and efficient synthesis for cis-δ-lactols with quaternary stereocenters in moderate yields with excellent enantioselectivity. Based on the selective precipitation of cis-δ-lactols, which were isolated by filtration, the catalytic system in the filtrate can be reused directly and recycled for eight times without any obvious deterioration in enantioselectivity.

Several novel prolylprolinol catalysts have been designed and synthesized. This type of compound showed high catalytic efficiency on promoting the direct addition of unmodified aldehydes to nitroalkenes. Among the catalysts surveyed, the least bulky member (8d) exhibited the best performance on both efficiency and stereoselectivity, providing the products with up to 97% ee value with 1.5–5 mol% catalyst loading. Additionally, computational studies of the transition state have been conducted to explain the high diastereo- and enantioselectivity.

Novel tricyclic 4-(trifluoromethyl)-[1,2,3]triazolo[1,5-a]quinoxalines were readily prepared from N-(o-haloaryl)alkynylimines and sodium azide via copper(I)-catalyzed tandem reactions. This synthetic strategy provides an efficient way to access a library of novel heterocyclic compounds that are of interest in drug discovery.

A highly enantioselective approach for preparing optically active bicyclic piperidines is described. The key step for introducing chiral centers was a L-proline catalyzed direct enantioselective aldol reaction of 3-phthalimidopropanal with aliphatic ketones. In the reactions with alicyclic ketones, a highly enantioselective formation of anti-2-(3-phthalimido-1-hydroxypropyl)cycloketones 1a–1b (>99% ee) was observed. The aldol products 1 could be subsequently converted into bicyclic piperidines 2 via a consecutive reductive deprotection, acylation, ring closure, and hydrolysis. Chirality, 2008. © 2008 Wiley-Liss, Inc.