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.

Directed carbometallation reactions of cyclopropenes are powerful reactions for the construction of functionalized cyclopropanes 1 -structures that have manifold applications in synthesis. 2 A number of effective carbomagnesation procedures have been described in recent years, 3 but a limitation has been the reactivity of Grignard reagents toward many functional groups. Most conspicuous has been the intolerance toward the ester functions of cyclopropenes (1) that are available from transition metal-catalyzed reactions of alkynes with α-diazo esters (Scheme 1). 4 Described herein are carbozincation reactions of cyclopropenes that are directed by ester or oxazolidinone substituents. This straightforward approach to cyclopropane synthesis proceeds with a stereochemical outcome that is complementary to that generally observed in catalytic cyclopropanation reactions of diazo compounds with alkenes. 5 It is well established that Cu-complexes can catalyze the conjugate addition reactions of organozinc reagents, and mechanistic proposals have invoked the cooperative action of Cu and Zn (Scheme 2a). 6 As cycloprop-2-ene carboxylates are homologs of α,β-unsaturated carbonyl compounds, it was hypothesized that esters would direct the carbozincation of cyclopropenes by analogy (Scheme 2b). Work by Gevorgyan, Rubin and Orchin has established that esters can be used as syn-directing groups 7 in catalytic hydroboration reactions 7a and in hydroformylation 7b-d reactions of cyclopropenes. Pioneering work by Negishi 8 and Nakamura 9 has established that allylzinc reagents add to cyclopropene derivatives. Nakamura has described an enantioselective Fe-catalyzed system for the addition of diorganozinc reagents to cyclopropenone ketals, 3c and Richey has described additions of Et 2 Zn to spiro[2.5]oct-1-enes. 10 However, facially selective carbozincations of cyclopropenes were unknown.From an optimization study directed toward the preparations of 3a-c, it was determined that additions of diorganozinc reagents could be effectively catalyzed by a variety of Cu(I) salts (see Supporting Information). CuI and CuCN were the most effective catalysts, and led to carbometallation products with excellent selectivity. Low conversions were observed and large excesses of organozinc reagents were required for additions carried out in the absence of a catalyst. An exception was 4b, which was formed in high yield with or without a catalyst. Solvent choice was an essential parameter: toluene was most effective, whereas the use of THF or diethyl ether lead to carbometallation products with low diastereoselectivity. The reactions with Ph 2 Zn were most effective in terms of reagent economy: 3c was obtained in 83% and 70% yields with 1.0 equiv and 0.6 equiv of Ph 2 Zn, respectively (Table 1). Larger amounts of Me 2 Zn (4.0 equiv) and Et 2 Zn (2.5 equiv) were required for optimal reactivity, as decreasing the amount of these organozinc reagents led to lower yields and increased side product formation.jmfox@udel.edu. Supporting Information Available: Fu...

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 N 2 . 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-member ring in the former compound. Calculations on the rearrangement of cycloprop-2-ene-1-oyl azides do not support π-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 N 2 to form a nitrene intermediate provides strong evidence that the concerted Curtius rearrangement is the dominant process.

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 transmetallation with ZnCl2.

Facially Selective Cu-Catalyzed Carbozincation of Cyclopropenes Using Arylzinc Reagents Formed by Sequential I/Mg/Zn Exchange. -In the presence of CuCN, various functionalized arylzinc compounds generated in situ undergo convenient and stereoselective coupling with the cyclopropene (II) to afford cis-substituted derivatives. Removal of Mg halide side products after transmetalation is necessary to achieve high diastereoselectivity and yield. Further functionalizations are possible which allow stereoselective formation of diverse polysubstituted cyclopropanes such as (VIII). -(TARWADE, V.; SELVARAJ, R.; FOX*, J. M.; J. Org. Chem. 77 (2012) 21, 9900-9904, http://dx.