Enantioselective Catalysis of the Aza-Cope Rearrangement by a Chiral Supramolecular Assembly

The chiral supramolecular catalyst Ga{sub 4}L{sub 6} [L = 1,5-bis(2,3-dihydroxybenzoylamino)naphthalene] is a molecular tetrahedron that catalyzes the 3-aza-Cope rearrangement of allyl enammonium cations. This catalysis is accomplished by preorganizing the substrate in a reactive conformation within the host. This work demonstrates that through the use of enantiopure assembly, its chiral cavity is capable of catalyzing the 3-aza-Cope rearrangement enantioselectively, with yields of 21-74% and enantiomeric excesses from 6 to 64% at 50 C. At lower temperatures, the enantioselectivity improved, reaching 78% ee at 5 C. This is the highest enantioselectivity to date induced by the chiral cavity of a supramolecular assembly

Gosteli-Claisen Rearrangement: DFT Study of Substituent-Rate Effects

The uncatalyzed Gosteli−Claisen rearrangement of four double bond isomeric allyl vinyl ethers has been studied at the B3LYP/6-31G* and B3LYP/6-31G*+PCM levels of theory. The experimentally determined structure−reactivity relationship was successfully reproduced; the relative reactivity of the (E,E)-, (E,Z)-, (Z,E)-, and (Z,Z)-configured allyl vinyl ethers can be attributed to unfavorable interactions caused by pseudoaxial substituents within the chairlike transition-state structures. As expected, the isolated assessment of the calculated ground-state or transition-state stabilities is not suitable to explain the experimentally observed structure−reactivity relationship

Enantioselective synthesis of the C-14 to C-5 cyclopentane segment of jatrophane diterpenes

The enantioselective synthesis of the C-14 to C-5 cyclopentane segment of jatrophane diterpenes is reported. An Evans aldol addition, a Horner–Wadsworth–Emmons olefination and a thermal intramolecular carbonyl ene reaction of an α-keto ester served as key C/C-connecting transformations. An Evans aldol addition and a thermal intramolecular carbonyl ene reaction of an α-keto esters are key steps in the asymmetric synthesis of the C-14 to C-5 segment of jatrophane diterpenes

Gosteli-Claisen Rearrangement: Substrate Synthesis, Simple Diastereoselectivity, and Kinetic Studies

The results of kinetic studies on the uncatalyzed [3,3]-sigmatropic rearrangement of 2-alkoxycarbonyl-substituted allyl vinyl ethers are reported. Apparently first reported by Gosteli in 1972, this variation of a Claisen rearrangement enjoyed a shadowy existence for three decades until its potential for the development of a catalytic asymmetric Claisen rearrangement was discovered. Inspired by this development, we have studied substituent and solvent rate effects, and we provide evidence that a chairlike transition state is highly favorable for the uncatalyzed Gosteli−Claisen rearrangement

{2,2-Bis[(4S)-4-tert-butyl-4,5-dihydro-1,3-oxazol-2-yl]propane}bis(N,N-dimethylformamide)copper(II) bis(hexafluoridoantimonate)

In the title compound, [Cu(C17H30N2O2)(C3H7NO)2][SbF6]2, which is a potential catalyst in the asymmetric Gosteli-Claisen rearrangement, the Cu atom adopts a distorted cis-CuN2O2 square-planar geometry arising from N,N'-bidentate coordination by the chiral ligand and two O-bonded dimethylformamide molecules. Two short C-HO contacts occur within the ligand and two weak intermolecular C-HF bonds may help to establish the packing

Organocatalytic Claisen Rearrangement: Theory and Experiment

A combined computational and experimental study on the Claisen rearrangement of a 2-alkoxycarbonyl-substituted allyl vinyl ether in the presence of thioureas as potential noncovalent organocatalysts has been performed. DFT calculations employing different basis sets were utilized to predict a catalytic cycle for the thiourea-catalyzed Claisen rearrangement. The nature of the transition state in the presence and absence of thioureas was studied in detail. Critical geometrical data of the transition state that are indicators for the relative barrier height of the Claisen rearrangement are discussed. Although we did observe a significant transition state stabilization, due to endergonic conformational changes and endergonic complexation the overall effect on the barrier is small, in accordance with experimental results

Integration of Catalysis and Analysis is the Key: Rapid and Precise Investigation of the Catalytic Asymmetric Gosteli-Claisen Rearrangement

The kinetics of the CuII(bisoxazoline)-catalyzed diastereo- and enantioselective Gosteli–Claisen rearrangement of 2-alkoxycarbonyl-substituted allyl vinyl ethers has been investigated by enantioselective on-column reaction gas chromatography (ocRGC). Enantioselective ocRGC integrates (stereoselective) catalysis and enantioselective chromatography in a single microcapillary, which is installed in a GC-MS for direct analysis of conversion and selectivity. Thus, this technique allows direct differentiation of thermal and stereoselectively catalyzed reaction pathways and determination of activation parameters and selectivities of the individual reaction pathways starting from stereoisomeric reactants with high precision. Two modes of operation of enantioselective ocRGC are presented to investigate noncatalyzed, i.e., conversion of isopropyl-2-(allyloxy)but-2Z-enoate 1 to isopropyl-3R,S-methyl-2-oxy-hex-5-enoate (±)-2 and the [Cu{(R,R)-Ph-box}](SbF6)2-catalyzed Gosteli–Claisen rearrangement, i.e., conversion of isopropyl-2-(but-2′E-en-1-yloxy)but-2Z-enoate (E,Z)-3 to isopropyl-3S,4S-dimethyl-2-oxy-hex-5-enoate 4b. Eyring activation parameters have been determined by temperature-dependent measurements: Uncatalyzed rearrangement of 1 to (±)-2 gives ΔG (298 K) = 114.1 ± 0.2 kJ·mol–1, ΔH = 101.1 ± 1.9 kJ·mol–1, and ΔS = −44 ± 5 J·(K·mol)−1, and catalyzed rearrangement of (E,Z)-3 to 4b gives ΔG (298 K) = 101.1 ± 0.3 kJ·mol–1, ΔH = 106.1 ± 6.6 kJ·mol–1, and ΔS = 17 ± 19 J·(K·mol)−1

Total Synthesis of Natural and Non-Natural Delta(5,6)Delta(12,13)-Jatrophane Diterpenes and Their Evaluation as MDR Modulators

We report the details of the total synthesis of natural and non-natural jatropha-5,12-dienes. The successful tactic for the assembly of the strained trans-bicyclo[10.3.0]pentadecane scaffold employed a B-alkyl Suzuki−Miyaura cross-coupling for the formation of the C5/C6 double bond and a ring-closing metathesis for the construction of the C12/C13 double bond. The key step of the synthesis of the cyclopentane fragment, an uncatalyzed intramolecular carbonyl−ene reaction, was studied computationally by DFT calculations. The members of the ensemble of synthetic natural and non-natural jatrophanes were subsequently examined as modulators for the ABCB1, ABCG2, and ABCC1 efflux proteins, which are associated with multidrug resistance in cancer chemotherapy