Possibility of [1,5] sigmatropic shifts in bicyclo[4.2.0]octa-2,4-dienes

The thermal equilibration of the methyl esters of endiandric acids D and E was subject to a computational study. An electrocyclic pathway via an electrocyclic ring opening followed by a ring flip and a subsequent electrocyclization proposed by Nicolaou [Nicolaou, K. C.; Chen, J. S. Chem. Soc. Rev. 2009, 38, 2993], was computationally explored. The free-energy barrier for this electrocyclic route was shown to be very close to the bicyclo[4.2.0]octa-2,4-diene reported by Huisgen [Huisgen, R.; Boche, G.; Dahmen, A.; Hechtl, W. Tetrahedron Lett. 1968, 5215]. Furthermore, the possibility of a [1,5] sigmatropic alkyl group shift of bicyclo[4.2.0]octa-2,4-diene systems at high temperatures was explored in a combined computational and experimental study. Calculated reaction barriers for an open-shell singlet biradical-mediated stepwise [1,5] sigmatropic alkyl group shift were shown to be comparable with the reaction barriers for the bicyclo[4.1.0]hepta-2,4-diene (norcaradiene) walk rearrangement. However, the stepwise sigmatropic pathway is suggested to only be feasible for appropriately substituted compounds. Experiments conducted on a deuterated analogous diol derivative confirmed the calculated (large) differences in barriers between electrocyclic and sigmatropic pathways

Recent Applications of the Simple Hydrocarbon Cyclooctatetrene as a Starting Material for Complex Molecule Synthesis

Cyclooctatetraene [COT], a simple non-aromatic cyclic polyene, is capable of undergoing a variety of oxidation and cycloaddition reactions to afford polycyclic structures. In addition, complexation of COT or the cycloaddition products with transition metals facilitates bond formation. Recent developments in the reactivity of COT and application to the synthesis of naturally occurring and non-naturally occurring compounds is reviewed

Total Synthesis of Kingianins A, D, and F

A synthesis fit for a king: The total synthesis of (±)-kingianinsA, D, and F has been achieved in ten steps. Key features include the gram-scale synthesis and partial reduction of a conjugated tetrayne to a (Z,Z,Z,Z)-tetraene, the domino 8π-6π electro

Does Koopmans\u27 Paradigm for 1-Electron Oxidation Always Hold? Breakdown of IP/Eox Relationship for p-Hydroquinone Ethers and the Role of Methoxy Group Rotation

Koopmans’ paradigm states that electron loss occurs from HOMO, thus forming the basis for the observed linear relationships between HOMO/IP, HOMO/Eox, and IP/Eox. In cases where a molecule undergoes dramatic structural reorganization upon 1-electron oxidation, the IP/Eox relationship does not hold, and the origin of which is not understood. For example, X-ray crystallography of the neutral and cation radicals of bicyclo[2.2.1]heptane-annulated p-hydroquinone ethers (THE and MHE) showed that they undergo electron-transfer-induced conformational reorganization and show breakdown of the IP/Eox relationship. DFT calculations revealed that Koopmans’ paradigm still holds true because the electron-transfer-induced subtle conformational reorganization, responsible for the breakdown of IP/Eox relationship, is also responsible for the reordering of HOMO and HOMO-1. Perceived failure of Koopmans’ paradigm in cases of THE and MHE assumes that both vertical and adiabatic electron detachments involve the same HOMO; however, this study demonstrates that the vertical ionization and adiabatic oxidation occur from different molecular orbitals due to reordering of HOMO/HOMO-1. The underpinnings of this finding will spur widespread interest in designing next-generation molecules beyond HQEs, whose electronic structures can be modulated by electron-transfer-induced conformation reorganization

Reactivity of (Bicyclo[5.1.0]octadienyl)iron(1+) Cations: Application to the Synthesis of cis-2-(2’-carboxycyclopropyl)glycines

The addition of carbon and heteroatom nucleophiles to (bicyclo[5.1.0]octadienyl)Fe(CO)2L+ cations 5 or 8 (L = CO, PPh3) generally proceeds via attack at the dienyl terminus on the face of the ligand opposite to iron to generate 6-substituted (bicyclo[5.1.0]octa-2,4-diene)iron complexes (11 or 13). In certain cases, these products are unstable with respect to elimination of a proton and the nucleophilic substituent to afford (cyclooctatetraene)Fe(CO)2L (4 or 7). Decomplexation of 13f, arising from addition of phthalimide to 8, gave N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (19). Oxidative cleavage of 19 (RuCl3/NaIO4) followed by esterification gave the cyclopropane diester 22, which upon hydrolysis gave cis-2-(2‘-carboxycyclopropyl)glycine (CCG-III, 18) (eight steps from 4, 43% overall yield). This methodology was also utilized for preparation of stereospecifically deuterated CCG-III (d-18) and optically enriched (−)-18. Deprotonation of 22 resulted in cyclopropane ring opening to afford the benzoindolizidine (23)

Does Koopmans’ Paradigm for 1-Electron Oxidation Always Hold? Breakdown of IP/E\u3csub\u3eox\u3c/sub\u3e Relationship for \u3cem\u3ep\u3c/em\u3e-Hydroquinone Ethers and the Role of Methoxy Group Rotation

Koopmans’ paradigm states that electron loss occurs from HOMO, thus forming the basis for the observed linear relationships between HOMO/IP, HOMO/Eox, and IP/Eox. In cases where a molecule undergoes dramatic structural reorganization upon 1-electron oxidation, the IP/Eoxrelationship does not hold, and the origin of which is not understood. For example, X-ray crystallography of the neutral and cation radicals of bicyclo[2.2.1]heptane-annulated p-hydroquinone ethers (THE and MHE) showed that they undergo electron-transfer-induced conformational reorganization and show breakdown of the IP/Eox relationship. DFT calculations revealed that Koopmans’ paradigm still holds true because the electron-transfer-induced subtle conformational reorganization, responsible for the breakdown of IP/Eox relationship, is also responsible for the reordering of HOMO and HOMO-1. Perceived failure of Koopmans’ paradigm in cases of THE and MHE assumes that both vertical and adiabatic electron detachments involve the same HOMO; however, this study demonstrates that the vertical ionization and adiabatic oxidation occur from different molecular orbitals due to reordering of HOMO/HOMO-1. The underpinnings of this finding will spur widespread interest in designing next-generation molecules beyond HQEs, whose electronic structures can be modulated by electron-transfer-induced conformation reorganization

Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Aminobicyclo[5.1.0]octitols

A series of eight stereoisomeric N-(tetrahydroxy bicyclo-[5.1.0]oct-2S*-yl)phthalimides were prepared in one to four steps from N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (±)-7, which is readily available from cyclooctatetraene (62 % yield). The structural assignments of the stereoisomers were established by 1H NMR spectral data as well as X-ray crystal structures for certain members. The outcomes of several epoxydiol hydrolyses, particularly ring contraction and enlargement, are of note. The isomeric phthalimides as well as the free amines did not exhibit β-glucosidase inhibitory activity at a concentration of less than 100 μM