Three-component coupling reactions between trialkylphosphines, methyl propiolates, and aldehydes produced 1:1:1 dipolar adducts in moderate-to-excellent yields. The product phosphonium enolate zwitterions were isolated as crystalline solids. X-ray crystallographic analyses of these single crystals established unequivocally the dipolar structures of these tetravalent phosphonium enolate zwitterions. Because phosphonium enolates are the first key intermediates in the nucleophilic phosphine-mediated catalysis of α,β-unsaturated carbonyl compounds, this study provides crucial insight into the mechanisms of Morita-Baylis-Hillman-type reactions.Phosphine-catalyzed reactions of electron-deficient alkenes have emerged as powerful tools for the preparation of biologically and medicinally useful compounds. 1,2 Common to these transformations is the generation of a putative dipolar phosphonium enolate through the addition of a tertiary phosphine to an electrophilic alkene. Focusing on the use of allenoates as substrates, we have explored the various reactions available for the key zwitterionic intermediates and have developed new methods for the syntheses of tetrahydropyridines, dihydropyrroles, dioxanes, and pyrones. 3 In those studies, the reaction pathways of the proposed intermediates could be controlled by varying the nature of the electrophile 4 or the structure of the initial zwitterionic adduct by using a bulky phosphine. 3d Although this approach has proved fruitful, leading to the discovery of an array of new reactions, we and others have never directly observed any of the conjectured zwitterionic intermediates. 5 Given the pivotal mechanistic roles played by phosphonium enolate intermediates, knowledge of their structures and reactivities will greatly benefit the further development of phosphine-catalyzed reactions. Herein, we report the syntheses of stable tetravalent phosphonium enolates through simple one-pot, three-component processes and the X-ray crystallographic characterization of these dipolar intermediates.Structural studies of tetravalent phosphonium zwitterions are complicated by the ability of their phosphorous atoms to adopt multiple valence structures. In particular, β-phosphonium enolates arising from the addition of trivalent phosphines to α,β-unsaturated carbonyl compounds are unstable and exist mainly as isomeric pentavalent phosphoranes (eqs 1 and 2). 6 For this reason, whereas a number of 1,2-λ 5 -oxaphospholenes have been characterized well, 7 direct observation of tetravalent phosphonium enolates has remained an elusive goal, even though the mechanistic implications for various phosphine-catalyzed processes would be immense. 8 ohyun@chem.ucla.edu. Following our interest in the chemistry of vinyl phosphonium enolates (eq 2) vis-à-vis that of alkyl derivatives (eq 1), 2, 3 we pondered the reactivity of a further type of vinyl phosphonium zwitterion: one derived from an electron-deficient alkyne (eq 3). We were particularly intrigued to examine its potential to undergo addition to an ...

[reaction: see text] A phosphine-catalyzed reaction of an allenoate with aldehydes furnished (2,6-diaryl-[1,3]dioxan-4-ylidene)-acetates 4 in excellent to moderate yields with complete diastereoselectivity and high E/Z-selectivities. Upon removal of the acetal functionality in this domino reaction product 4, delta-hydroxy-beta-ketoester 11 was obtained. The reported vinylphosphonium-based approach provides a new way to achieve a synthesis of delta-hydroxy-beta-ketoesters that differs from the classical dianion-based approach.

We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]heptanes from naturally occurring trans-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities. These two diastereoisomeric phosphines functioned as pseudoenantiomers, providing their chiral pyrrolines with opposite absolute configurations.

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Ecto-ATPase (CD39L1) corresponds to the type 2 enzyme of the ecto-nucleoside triphosphate diphosphohydrolase family (E-NTPDase). We have isolated from human ECV304 cells three cDNAs with high homology with members of the E-NTPDase family that encode predicted proteins of 495, 472, and 450 amino acids. Sequencing of a genomic DNA clone confirmed that these three sequences correspond to splice variants of the human ecto-ATPase (NTPDase2␣, -2␤, and -2␥). Although all three enzyme forms were expressed heterologously to similar levels in Chinese hamster ovary cells clone K-1 (CHO-K1) cells, only the 495-amino acid protein (NTPDase2␣ exhibited ecto-ATPase activity. Immunolocalization studies demonstrated that NTPDase2␣ is fully processed and trafficked to the plasma membrane, whereas the NTPDase2␤ and -2␥ splice variants were retained in not fully glycosylated forms in the endoplasmic reticulum. The potential roles of two highly conserved residues, Cys 399 and Asn 443 , in the activity and cellular trafficking of the ecto-ATPase were examined. Mutation of Cys 399 , which is absent in NTPDase2␤ and -2␥, produced a protein completely devoid of nucleotidase activity, while mutation of Asn 443 to Asp resulted in substantial loss of activity. Neither the Cys 399 nor Asn 443 mutants were fully glycosylated, and both were retained in the endoplasmic reticulum. These results indicate that the lack of ecto-nucleotidase activity exhibited by NTPDase2␤ and -2␥ and the C399S mutant, as well as the large reduction of activity in the N443D mutant are due to alterations in the folding/maturation of these proteins.Extracellular nucleotides modulate many physiological responses through interaction with G protein-coupled metabotropic receptors (P2Y) and ligand-gated ionotropic receptors (P2X) (1-3). Termination of nucleotide-promoted signaling is accomplished by rapid degradation and/or interconversion of extracellular nucleotides by ecto-nucleotidases. Although the primary function of ecto-nucleotidases involves the hydrolysis of extracellular nucleotides, the complete physiological significance of these enzymes is not fully understood. For example, ecto-nucleotidases also have been implicated in physiological phenomena as diverse as cell adhesion (4), purine recycling (5), pain transmission (6), immune function (7), blood hemostasis (8), and others (9, 10).The ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) 1 are a family of ecto-nucleotidases, including ecto-ATPases and ecto-ATPDases (apyrases), that hydrolyze nucleoside 5Ј-tri-and diphosphates with isozyme-dependent nucleotide selectivities and biochemical properties. The E-NTPDase family includes membrane-associated enzymes (NTPDase1 to NTPDase4) and soluble enzymes (NTPDase5 and NTPDase6) (see Zimmermann (10) for a review). NTPDase2 (also known as ecto-ATPase or CD39L1) exhibits a strong preference for nucleoside triphosphates (NTPs) over diphosphates (nucleoside diphosphates), hydrolyzing nucleoside diphosphates at 3-5% of the rate of NTPs (10 -14). NTPDase2 contai...