Showing papers by "Leo A. Paquette published in 1999"

Synthesis of Enantiopure C2-Symmetric VERDI Disulfonamides and Their Application to the Catalytic Enantioselective Addition of Diethylzinc to Aromatic and Aliphatic Aldehydes

Abstract: The enantiopure disulfonamides 7a−c have been prepared from the C2-symmetric diketone 2, a starting material conveniently accessible from the “dimerization” of (+)-verbenone. These ligands, when treated with titanium isopropoxide and diethylzinc, function as catalysts for the enantioselective alkylation of aldehydes. Stereoselectivity levels ranging from 72 to 98% ee are seen depending on the structural characteristics of the aldehyde. In all cases, the absolute configuration of the carbinol product is R. A working mechanistic model is advanced for the purpose of rationalizing the high levels and direction of asymmetric induction exhibited by these VERDI catalysts.

Intramolecular Cyclization of Radicals Generated from α-Halomethylsulfonamides

Abstract: A series of homologous α-sulfonamidyl radicals has been generated by reaction of α-halomethyl precursors with tri-n-butyltin hydride under AIBN catalysis. The intramolecular cyclization capability of these highly reactive intermediates has been evaluated. Where possible, five-membered sultams are formed by 5-exo transition states. The longer C−SO2 and SO2−NR2 bonds have little demonstrable effect on this pathway. In larger systems, however, the 7-endo option predominates over the 6-exo alternative. A preparatively useful route to sultams has emerged from this investigation.

Intramolecular Cyclization of Tethered Phenyl Ketones. Complementary Stereochemical Results Arising from the Indium-Promoted Ring Closure of Allyl Bromides and the Fluoride Ion-Induced Desilylation of Allylsilanes.

Abstract: The intramolecular indium-promoted cyclization of 4‘-substituted (Z)- and (E)-7-bromo-5-heptenophenones has been examined in aqueous tetrahydrofuran. In every instance, ring closure occurred to deliver the syn-2-vinylcyclopentanol exclusively. The corresponding allylsilanes have been prepared as well, and the course of their fluoride ion-induced cyclization was also studied. In these systems, a kinetic bias for formation of the anti-2-vinylcyclopentanol is observed, although not with the same exclusivity. Accordingly, complementarity in product diastereoselectivity can be realized in purposeful fashion. The data acquired in this investigation suggest that the indium-catalyzed reactions involve intramolecularly coordinated transition states where development of a cis 5/6-bicyclic framework is most energetically feasible. In contrast, the silanes appear to utilize open-chain antiperiplanar transition states. While the latter are not particularly sensitive to double-bond geometry, they are responsive to ster...

A Direct, Highly Convergent Route to α-Methylene-γ-lactones Fused to Medium and Large Rings.

Abstract: A general procedure for the synthesis of α-methylene lactones cis- or trans-fused to larger rings is described. The convenient approach originates with two ω-unsaturated aldehydes of the same or different chain length.

Synthesis of Stereodefined Z‐Vinyl Iodides from Carbohydrates as a Prelude to C/D Ring Assembly in Taxanes.

Abstract: D -Mannitol has been transformed into 10 and 14 , while D -glucose has served as precursor to 20 . In the latter example, key steps include stereocontrolled vinylation, oxidative fragmentation of the tetrahydrofuran-2,3-diol, oxetane ring closure, and highly stereoselective iodoolefination.

A Modular Enantioselective Approach to Construction of the Macrolactone Core of Polycavernoside A.

Abstract: A program directed toward a total synthesis of polycavernoside A is described The synthesis of five building blocks is detailed The first of two electrophilic units, the lactone 3, was prepared in four steps from the known enantiomerically pure oxirane 15 Pyranyl aldehyde 5 was elaborated in turn from l-malic acid via 10 While the route to 30 involved 3 as a starting material, dithiane 2 was obtained in a straightforward manner from 10 as well The merging of the chiral sectors could not be accomplished by way of the lithiated dithianyl anions, presumably as a consequence of their heightened basicity The strategic incorporation of the trienyl sector was accomplished, although no attempt was made to control the diastereoselectivity of the process

An Indium‐Promoted Alternative to the Knoevenagel Condensation of Aldehydes with Methyl Acetoacetate.

Abstract: Addition of methyl (E)-4-bromo-3-methoxycrotonate to aldehydes in the presence of indium and water delivers β-hydroxy esters, acidic hydrolysis of which leads to Knoevenagel-like adducts

Allylindation of 6‐Substituted 2‐Hydroxy‐1‐tetralones in Aqueous and Organic Media. Stereochemistry and Competition Studies.

Abstract: A systematic investigation of the stereoselectivity associated with coupling reactions involving the allylindium reagent and 6-substituted 2-hydroxy-1-tetralones is presented. In each instance, the allylations were carried out in water, 50% aqueous THF, and dry THF. The extent of 1,2-induction was found to be highest in THF−H2O (1:1) and to favor the trans diol isomer. Somewhat lower levels of stereochemical bias in the same direction were observed in pure water. However, further erosion of this trend was noted for those reactions performed in THF, such that a modest crossover in product distribution became apparent in certain examples. On the basis of competition experiments, both reaction trajectories give evidence of proceeding via chelated intermediates. The extent of stereoinduction was found to be in line with the normal predilection of 2-cyclohexenones for axial attack, which is the process believed to be beset with minimal torsional effects. The substituents situated para to the ketone carbonyl do...