An efficient bisphosphine-catalysed sequential [4+2]/[4+2] annulation reaction of a γ-benzyl allenoate with benzylidenepyrazolones has been developed. Under the catalysis of DPPB [1,3-bis(diphenylphosphanyl)butane], the [4+2]/[4+2] annulation proceeded smoothly to give spiro-pyrazolidinone derivatives in moderate yields. This protocol provides a simple and practical strategy for the construction of highly substituted 2H-spiro[naphthalene-pyrazole] skeletons.

The asymmetric vinylogous Mukaiyama aldol reaction between α-keto phosphonate and 2-(trimethylsilyloxy)furan was performed by using bis(oxazoline)-copper complexes as the catalyst and 2,2,2-trifluoroethanol as additive in dichloromethane. The present method is highly tolerable for functionalized α-keto phosphonates and enabled us to obtain the corresponding 3- and 4-substituted benzyl-functionalized tertiary α-hydroxy phosphonates in high yields (up to 86%) as well as high enantiostereoselectivities (up to 98% ee) and diastereoselectivities (up to 99:1, anti-selective).

The coupling reactions of various N, O, and S nucleophilic reagents with aryl halides have been successfully carried out under mild conditions by using a novel chiral N,N′-dioxide–copper(I) catalytic system as the catalyst. This versatile and efficient catalyst system has been demonstrated to facilitate the cross-coupling reactions of aryl halides with amines,phenols, and thiols to afford the corresponding desired products in good to excellent yields.

A convenient diastereoselective synthesis of diisopropyl (2R,3R)-3-{{{(R/S)-aryl[(diethoxyphosphinyl)amino]methyl}hydroxyphosphinyl}oxy}-2-hydroxybutanedioate through Mannich-type reactions is reported. The reactions take place under mild conditions in good yields, and this makes it possible to introduce various substituents at the α-position to the P-atom of α-aminophosphonates. The chiral diisopropyl (4R,5R)-2-chloro-1,3,2-dioxaphospholane-4,5-dicarboxylate (3) was found to be a good phosphonylating agent in this stereoselective reaction.

The diastereospecific formation of dihydropyrimidines (DHPMs) has been achieved in moderate to high yields with up to 99% ee by a Biginelli reaction. The reaction was performed by using a combined catalyst consisting of a chiral bifunctional primary amine-thiourea 9f and a Brønsted acid with tert-butylammonium trifluoroacetate (t-BuNH₂⋅TFA) as additive in dichloromethane at room temperature. The possible mechanism for the reaction has been proposed to explain the origin of the activation and the asymmetric induction.

The tandem nucleophilic addition-cyclization reaction of o-alkynylbenzaldehydes or o-alkynylacetophenones 2 with dialkyl phosphites or dialkyl phosphonothioates 1 took place very smoothly in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in THF at room temperature. In all cases, the reaction proceeded in a regioselective manner leading to the 5-exo-dig products 3 in excellent yields. The phenomenon of a 1,5-sigmatropic hydrogen shift or a 1,5-sigmatropic methyl shift was observed in this reaction depending on the different substituent groups such as R³ in the o-alkynylbenzaldehyde or o-alkynylacetophenone 2 substrates.

The diastereospecific formation of β-N-glycosidically linked α-aminophosphonic acids derivatives has been achieved with high yield via a Mannich-type reaction. The reaction was performed by using O-pivaloylated galactosylamine 1 as a chiral template and boron trifluoride diethyl etherate as a catalyst in THF. Imines 3 of aromatic compounds and diethyl phosphite were converted to N-galactosyl α-aminoalkylphosphonate 4, giving ratios of diastereomers higher than 19:1. This procedure provides a rapid access to biologically important galactosyl α-aminophosphonic acids derivatives.

An efficient and green method to the synthesis of N-protected o-hydroxylphenyl α-amino-alkylphosphonic monoesters is described. It consists of the three-component Mannich-type reaction of phosphoramides, carbonyl compounds (aldehydes or ketones), and 2-chlorobenzo[1,3,2] diox-aphospholes under solvent-free and catalyst-free conditions, followed by hydrolysis. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:596–601, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20483