Facially selective Cu-catalyzed carbozincation of cyclopropenes using arylzinc reagents formed by sequential I/Mg/Zn exchange.

Described is a Cu-catalyzed directed carbozincation of cyclopropenes with organozinc reagents prepared by I/Mg/Zn exchange. This protocol broadens the scope with respect to functional group tolerance and enables use of aryl iodide precursors, rather than purified diorganozinc precursors. Critical to diastereoselectivity of the carbozincation step is the removal of magnesium halide salts after transmetalation with ZnCl(2).

Directed carbozincation reactions of cyclopropene derivatives.

A diastereoselective procedure has been developed for the Cu-catalyzed addition of diorganozinc reagents to cyclopropene derivatives. Ester and oxazolidinone functions direct the addition of a variety of organozinc reagents with excellent facial selectivity. The resulting cyclopropylzinc reagents can be captured via stereospecific reactions with electrophiles. Cycloprop-2-ene carboxylic esters, which are directly available from the transition-metal-catalyzed reactions of alkynes with alpha-diazo esters, can be utilized directly in carbozincation protocols. Both diastereoselectivity and regioselectivity are high for the carbozincation reactions of 2-alkylcycloprop-2-ene carboxylate esters. The scope of the method is broadened by the ability to utilize organozinc reagents that have been generated in situ from Grignard reagents. Chiral oxazolidinone auxilaries are effective in controlling the diastereoselectivity of the carbometalation reactions.

The Curtius rearrangement of cyclopropyl and cyclopropenoyl azides. A combined theoretical and experimental mechanistic study.

A combined experimental and theoretical study addresses the concertedness of the thermal Curtius rearrangement. The kinetics of the Curtius rearrangements of methyl 1-azidocarbonyl cycloprop-2-ene-1-carboxylate and methyl 1-azidocarbonyl cyclopropane-1-carboxylate were studied by (1)H NMR spectroscopy, and there is close agreement between calculated and experimental enthalpies and entropies of activation. Density functional theory (DFT) calculations (B3LYP/6-311+G(d,p)) on these same acyl azides suggest gas phase barriers of 27.8 and 25.1 kcal/mol. By comparison, gas phase activation barriers for the rearrangement of acetyl, pivaloyl, and phenyl azides are 27.6, 27.4, and 30.0 kcal/mol, respectively. The barrier for the concerted Curtius reaction of acetyl azide at the CCSD(T)/6-311+G(d,p) level exhibited a comparable activation energy of 26.3 kcal/mol. Intrinsic reaction coordinate (IRC) analyses suggest that all of the rearrangements occur by a concerted pathway with the concomitant loss of N2. The lower activation energy for the rearrangement of methyl 1-azidocarbonyl cycloprop-2-ene-1-carboxylate relative to methyl 1-azidocarbonyl cyclopropane-1-carboxylate was attributed to a weaker bond between the carbonyl carbon and the three-membered ring in the former compound. Calculations on the rearrangement of cycloprop-2-ene-1-oyl azides do not support pi-stabilization of the transition state by the cyclopropene double bond. A comparison of reaction pathways at the CBS-QB3 level for the Curtius rearrangement versus the loss of N2 to form a nitrene intermediate provides strong evidence that the concerted Curtius rearrangement is the dominant process.

Abiotic metallofoldamers as electrochemically responsive molecules.

Described are the design, synthesis, and study of nonbiological molecules based on salophen and salen ligands that fold into single-stranded helices in the presence of either Ni(II) or Cu(II). X-ray diffraction studies show that the materials fold into helical structures in the solid state, and a series of NMR studies provide strong evidence that the folded structures are conserved in solution. Metal coordination is required for folding, as NMR and X-ray show that the free ligands do not adopt helical structures. Two of the racemic metallofoldamers spontaneously resolve during crystallization from CHCl3/acetonitrile, and CD spectroscopy and optical rotation show that the resolved, crystalline materials racemize quickly when dissolved at 5 degrees C. This shows that the secondary structures can reorganize easily and can, therefore, provide the basis for responsive materials. By comparison, an analogue from enantiomerically pure (R,R)-(-)-trans-cyclohexanediamine showed a strong CD signal and a large specific rotation. Electrochemical experiments show that a structural reorganization occurs upon metal-centered reduction of a Cu(II)-containing foldamer. When the reduction is carried out in the presence of coordinating ligands, it is proposed that apical binding of those ligands gives square pyramidal complexes. Semiempirical (AM1) calculations support that the helical structure would be disrupted by the reduction to Cu(I) with concomitant reorganization to a square pyramidal complex.