New synthetic routes to strained cumulenes and reactive carbenes

I. The synthesis, trapping, and strain energy estimates for cyclic butatrienes are described. Four fundamental questions have been investigated: kinetic stability limitations, molecular strain, structural limitations, and the development of a general synthetic route applicable to different ring sizes. 1,2,3-Cyclooctatriene (9) has been generated by magnesium induced 1,2-elimination on 2-bromo-3-chloro-1,3-cyclooctadiene (4). Synthesis of the eight-membered ring completes the C\sb6-C\sb{10} series of cyclic butatrienes. This substance shows moderate kinetic stability, but is readily trapped in a (\rm\sb\pi2\sb{s}{+}\sb\pi4\sb{s}\rbrack cycloaddition with diphenylisobenzofuran or 2,5-dimethylfuran. The total strain energy and the strain in the butatriene moiety in cumulene 9 have been assessed by ab initio calculations. The estimates are 17.7 kcal/mol and 12.4 kcal/mol, respectively, at the MP2/6-31G*//HF/3-21G level. 1,2,3-Cycloheptatriene (0) and its isomer cyclohepten-3-yne (9) are readily accessible by magnesium induced 1,2-elimination on appropriate precursors. The calculated total strain energy in the cyclic butatriene, and in the seven-membered enyne are 31.8 kcal/mol and 30.8 kcal/mol, respectively, at the MP2/6-31G*//HF/3-21G level. 5,5-Dimethyl-1,2,3-cyclopentatriene (5) remains elusive. Five likely precursors have been prepared and studied; no evidence for the existence of this compound was found. Intramolecular vinylidene coupling has been explored as a possible ring-size-independent synthetic route to cyclic butatrienes. In the cases of tetrabromo-olefins 22 and 27 a 1,2-migration occurs faster than the ring closure which would give the cumulene. II. A general route to cleanly photogenerate reactive carbenes by photolysis of cyclopropanated phenanthrenes has been studied. The adduct of dichlorocarbene and phenanthrene has been modified to produce shelf-stable substances that serve as photochemical precursors to vinylcarbene, and acyclic and cyclic vinylidenes. Low temperature irradiation of 7-endo-ethylenedibenzo (a;b) bicyclo (4.10) heptane (41) at 254 nm cleanly gives phenanthrene (35) and vinylcarbene (36); the latter rapidly rearranges to cyclopropene. The strained alkene is efficiently trapped by cycloadditions with cyclopentadiene or diphenylisobenzofuran. Fragmentation of a C\sb9 vinylidene precursor 58 leads to efficient formation of 1-nonyne (60) by 1,2-shift. Cyclobutylidenecarbene (63) rearranges readily to cyclopentyne (3). Cycloalkyne 3 is trapped by cyclohexene to give tricyclo (6.3.0.0\sp{2,7}\rbrackundec-1(8)-ene (68) and a cyclohexyl derivative 72 which has not been previously described. Rearrangements of cyclopentylidenecarbene (63) and cyclohexylidenecarbene (64) are not observed. These carbenes are trapped in (2+1) cycloadditions with cyclohexene

I Asymmetric photochemistry II Exploratory and mechanistic studies on the triplet sensitized vapor phase photochemistry of allenes III Developments in the synthesis of strained cyclic cumulenes

The development and implementation of a new chiral triplet sensitizer derived from 1,1\sp\prime-binaphthol is described. Irradiation of 1,3-diphenylallene (16) in the presence of 4,5,6,7-tetrahydro-dinaphtho(2,1-g:1\sp\prime,2\sp\prime-i) (1,6) dioxecine (10) resulted in 0.66% optical induction. Irradiation of 1,3-cyclooctadiene (17) in the presence of 10 resulted in 11.3% optical induction. The singlet state of 10 could be effectively quenched by higher diene concentration, substantially reducing the optical yield. Irradiation of trans-1,2-diphenyl-cyclopropane (1) in the presence of 10 resulted in very low optical yields. The mechanism by which triplet excited state allenes react in the vapor phase is investigated through both theory and experiment. Benzene sensitized vapor phase irradiation of cyclohexylallene (63) yields cis and trans-1,3,8-nonatriene (82) as the primary products. Triene 82 undergoes triplet sensitized (4+2) cycloaddition reactions yielding bicyclic alkenes 45 and 83. Additionally, 82 undergoes a series of triplet sensitized (2+2) cycloadditions, yielding bicyclic alkenes 84-86. The absence of any observed tricyclics argues for the intermediacy of planar triplet allene 89, instead of triplet cyclopropylidene 88. Benzene sensitized vapor phase irradiation of vinylidenecycloheptane (64) yielded only starting material. Models indicated that neither intermediate, triplet cyclopropylidene 99 or planar triplet allene 100, was particularly well suited for hydrogen abstraction to occur. Benzene sensitized solution phase irradiation of either 63 or 64 yielded only starting material. Ab initio calculations at the UMP3/6-31G*//UHF/3-21G level are reported for hydrogen abstraction from methane by triplet cyclopropylidene (52), and planar triplet allene (61). The calculations predict E\sb{\rm a} = 16.7 and 18.8 kcal/mol for hydrogen abstraction by 52 and 61, respectively. The syntheses and trapping of 1-phenyl-1,2-cyclohexadiene (137) is described. Several pathways directed toward the synthesis of 1,2-cyclopentadiene (131) are also described. Additionally, the development of a new, and presumably general route to cyclic allenes is presented. The syntheses and trapping of 1,2,3-cyclohexatriene (199) and cyclohexen-3-yne (240) are described. Both are prepared by introduction of the strained $\pi$ bond through fluoride induced elimination of vicinal trimethylsilyl, and triflate or halide groups. Both syntheses are general and should be applicable to different ring sizes

Versatility of the Cyano Group in Intermolecular Interactions

Several cyano groups are added to an alkane, alkene, and alkyne group so as to construct a Lewis acid molecule with a positive region of electrostatic potential in the area adjoining these substituents. Although each individual cyano group produces only a weak π-hole, when two or more such groups are properly situated, they can pool their π-holes into one much more intense positive region that is located midway between them. A NH3 base is attracted to this site, where it forms a strong noncovalent bond to the Lewis acid, amounting to as much as 13.6 kcal/mol. The precise nature of the bonding varies a bit from one complex to the next but typically contains a tetrel bond to the C atoms of the cyano groups or the C atoms of the linkage connecting the C≡N substituents. The placement of the cyano groups on a cyclic system like cyclopropane or cyclobutane has a mild weakening effect upon the binding. Although F is comparable to C≡N in terms of electron-withdrawing power, the replacement of cyano by F substituents substantially weakens the binding with NH3

Cyclopropylmethyldiphosphates are substrates for sesquiterpene synthases: experimental and theoretical results

New homo-sesquiterpenes are accessible after conversion of presilphiperfolan-8β-ol synthase (BcBOT2) with cyclopropylmethyl analogs of farnesyl diphosphate, and this biotransformation is dependent on subtle structural refinements. Two of the three cyclisation products are homo variants of germacrene D and germacrene D-4-ol while the third product reported contains a new bicyclic backbone for which no analogue in nature has been described so far. The findings on diphosphate activation are discussed and rationalised by relaxed force constants and dissociation energies computed at the DFT level of theory

Theoretical and experimental studies of reactive organic molecules

Chapter I. Density functional theory calculations were used to examine the interconversions of C5H6 and C 6H8 isomers. On the C5H6 surface, cyclobutenylcarbene is predicted to rearrange to 1,2-cyclopentadiene. Interconversion of cyclobutylidenecarbene and cyclopentyne has a small barrier. For the C6H8 surface, cyclopentenylcarbene is predicted to rearrange to bicyclo[3.1.0]hex-5-ene and further to 1,3-cyclohexadiene. Cyclopentylidenecarbene can easily interconvert with cyclohexyne. These results are in accord with experimental results, to date. Carbene precursors via a cyclopropanated phenanthrene, 1,1-dihalo-1a,9b-dihydro-1H-cyclopropa[I]phenanthrene, were studied. Chapter II. Isodesmic and homodesmic equations at B3LYP/6-311+G(d,p) level of theory have been used to estimate strain for the series of cyclic allenes and cyclic butatrienes. A fragment strain approach was also developed and provides more accurate predictions for the larger rings. The strain estimations are in agreement with experimental results for these cumulenes. Chapter III. We have mapped the energy surface for the ozone + ketone reaction with B3LYP, BH&HLYP, CCSD(T) and CBS-QB3 methods. Oxidation by ozone renders aldehydes unsuitable for examining the tetroxolane hypothesis. (Abstract shortened by UMI.)

Conformational properties of molecules by ab initio quantum mechanical energy minimization.

The recent literature on the determination of minimum energy conformations by ab initio quantum mechanical techniques is reviewed. The availability of computer-coded analytical first and second derivatives of the Hartree-Fock energy makes possible calculations that will be of significant assistance in structure determination of molecules. A short review of recent progress in empirical energy minimization and molecular dynamics is provided

An unexpected Ireland–Claisen rearrangement cascade during the synthesis of the tricyclic core of Curcusone C: Mechanistic elucidation by trial-and-error and automatic artificial force-induced reaction (AFIR) computations

In the course of a total synthesis effort directed toward the natural product curcusone C, the Stoltz group discovered an unexpected thermal rearrangement of a divinylcyclopropane to the product of a formal Cope/1,3-sigmatropic shift sequence. Since the involvement of a thermally forbidden 1,3-shift seemed unlikely, theoretical studies involving two approaches, the “trial-and-error” testing of various conceivable mechanisms (Houk group) and an “automatic” approach using the Maeda–Morokuma AFIR method (Morokuma group) were applied to explore the mechanism. Eventually, both approaches converged on a cascade mechanism shown to have some partial literature precedent: Cope rearrangement/1,5-sigmatropic silyl shift/Claisen rearrangement/retro-Claisen rearrangement/1,5-sigmatropic silyl shift, comprising a quintet of five sequential thermally allowed pericyclic rearrangements