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The thermal [C.sup.2]-[C.sup.6] cyclization of the enyne-allenes and their ring-closed and ring-opened products is described using an ultrafast radical clock. The results have provided a direct evidence for a stepwise mechanism in the [C.sup.2]-[C.sup.6] cyclization of enyne-allenes.

The pseudo-Jahn-Teller (PJT) interactions occurring between two low-lying Jahn-Teller (JT) doubly degenerate electronic states of the prototypical cyclopropane radical cation ([CP.sup.+]) are studied. The analysis reveals vibronic level spectra and the ultrafast nonradiative decay of the excited cationic states are related to the highly complex entanglement of electronic and nuclear degrees of freedom in the prototypical molecular system.

An ab initio study is performed for the singlet-triplet gap in trimethylenmethane (TMM) and of the ring-opening of methylenecyclopropane by the multireference BWCC method. A multireference method is used because the singlet states of TMM and intermediates between TMM and methylenecyclopropane have a strong multiconfigurational character.

A general and highly efficient asymmetric synthesis of potent and selective bicyclo[3.1.0]hexanes mGluR2/3 agonists is described. Densely functionalized, enantiomerically pure, monoprotected diols were prepared through a Et3Al-mediated intramolecular cyclopropanation with respect H or F endo selectivity in excellent yields.

A report that regioselective distal bond cleavage of methylenecyclopropanes is accomplished, irrespective of the structure of the substituent R(super 1), by using the cyclic amides. The selectivity of the respective ring-opening position depends on the substituents of methylenecyclopropanes.

Quantitative evaluations of the aromaticity (antiaromaticity) of neutral exocyclic substituted cyclopropenes [(HC).sub.2]C=X (X = BH to InH), C[H.sub.2] to Sn[H.sub.2], NH to SbH are described. Electronegative X-based substituents are observed to increase the aromaticity of the cyclopropene rings, while electropositive substituents have the opposite effect.

Tetravinylbenzene is prepared in quantitative yield from tetrabromobenzene, where one-step procedure has used Suzuki-Miyaura cross-coupling conditions. Intramolecular cyclopropanation of monoadduct, putatively by its methyllithium-generated cyclopropylidene(oid) has produced a compound featuring a highly distorted spiropentane having a C-C-C bond angle.

Density functional theory (DFT) is used for examining the zinc carbenoid-mediated homologation reaction of [beta]-keto esters. Pathway B has explained the proposed, but spectroscopically unobservable donor-acceptor cyclopropane intermediate, while the second pathway A has disclosed an alternative to the classical intermediate in that a cyclopropane transition state leads to product.

A facile synthesis of 2-carbamoyl-2-cyanocyclopropanecarboxylates through a tandem iodosobenzene/tetrabutylammonium iodide-induced oxidative cyclization and a subsequent neighboring group-assisted decarboxylation of the Michael adducts of 2-cyanoacetamides with [alpha],[beta]-unsaturated malonates is described. The method is observed to proceed smoothly under mild conditions and with good functional group tolerance and could be used to obtain highly functionalized cyclopropanes in moderate to good yields and with excellent diastereoselectivities.

The rapid synthesis of 3,3-pyrollidinyl-spirooxindole cores from cyclopropyl spirooxindoles and aldehydes, amines and sulfonamides is described. This method has used microwave heating to access a biologically privileged scaffold in an efficient route amenable to library population.

The Pd-catalyzed cross-coupling of aryl bromides or triflates and cyclopropylmagnesium bromide in the presence of substoichiometric amounts of zinc bromide has produced cyclopropyl arenes. The cross-coupling of other alkyl, cycloalkyl and aryl Grignard reagents with aryl bromides under the same conditions have produced the corresponding substituted arenes.

A research program is developed for achieving synthesis of tetrahydrofurans from cyclopropanes and C[double bond]O [pi] bonds. Asymmetric syntheses of (+)-polyanthellin A and (+)-virgatusin are achieved, which have depended upon cyclopropane/aldehyde annulation for construction of the core tetrahydrofurans.

The preparation of precursors to [pi]-conjugated cyclopropenium polymers is described along with the electronic properties of cyclopropenone polymers in their pristine states and after acidification. The increased contributions of cyclopropenium cation aromaticity have restricted the quinodal charge carriers because of the enengetically less favorable proposition of disrupting the local aromatic stabilization.

The monomer derived from achiral 1-(aminoxy)cyclopropanecarboxylic acid (OAcc) and oligopeptides consisting of a chiral [alpha]-aminoxy acid and an achiral [alpha]-aminoxy acid like OAcc are prepared and their structures are analyzed. The studies have disclosed achiral aminoxy acid residues like the OAcc unit as a useful building block to be included into chiral aminoxy peptides to mimic chiral helix structure.

Both enantiomers of the DHFR inhibitor iclaprim (R)-1 and (S)-1 are prepared from the cyclopropyl homoallyl alcohols (R)-6 and (S)-6. The moderate enantioselectivity of the products (R)- and (S)-1 is related to the Mitsunobu reaction, which has not proceeded with complete inversion of configuration.

Alkylidenecyclopropanes is prepared from enantiomerically enriched cyclopropene derivatives with 99% stereotransfer. The protocol consists of the stereoselective reaction of Grignard reagents with 1-alkoxymethyl-3-hydroxymethylcyclopropenes and a stereospecific [1,3] carbon shift reaction.

Density functional theory calculations are used for studying the mechanism of rhodium(II)-catalyzed cyclopropanation reactions with ethyl bromo-, chloro-, and iododiazoacetate. The relative energies of the side-on trajectory transition states compared to the end-on trajectory transition states are affected by both the substrate alkene and the carbenoid substituents, which are used for predicting the stereochemical outcome of cyclopropanation reactions.

1,3-Dipolar cycloaddition reactions of VDCP-diesters with aromatic diazomethanes generated in situ from the aromatic aldehydes and tosylhydrazine mediated by base produce pyrazole derivatives under mild conditions. A plausible reaction mechanism is proposed based on the control experiments along with the discussion on the regioselectivity.

Rhodium(I)-catalyzed cyclopropanation reactions to efficiently convert nitrogen-tethered 1,6-enynes to azabicyclo[4.1.0]heptenes are reported. Rhodium(I)-catalyzed tandem cycloisomerization and carbonylative [3+3+1] cycloaddition reactions of a cyclopropylenyne are also reported.

The preparation of a new phosphate carbenoid [(n-BuO).sub.2]P(O)OZn[CH.sub.2]I and its application in organozinc-mediated reactions is described. The application of obtained carbenoid in the chain extension of 1,3-diketones and [2,3]-sigmatropic rearrangement reactions is also described.

The conversion of cyclopropane-fused carbohydrates into oxepines is a good method for accessing diverse members of the septanoside family of carbohydrate mimetics. 2-Bromooxepines are obtained via silver(I)-promoted thermal ring expansion of a D-glucal-derived gem-dihalocyclopropanated sugar and cyclopropane ring cleavage under basic conditions has led to 2-C-branched pyranosides.

Functionalized arenes are prepared by chelation-controlled [3+3] cyclization/cyclopropane opening reactions of 1-trimethylsilyloxy-1,3-butadienes with benzyloxy- or methoxy-substituted 1,1-diacyclopropanes. Mixed chromanes-isochromanes are prepared by using 1,3-bis(silyloxy)-1,3-butadie nes containing a remote chloride group.

Ag(I)-catalyzed intramolecular reaction of monoarylmethylenecyclopropanes (MCPs) tethered with 1,1,3-triarylprop-2-yn-1-ols which provides diastereoselective access to polysubstituted allenylcyclobutanols is reported. The obtained Au(I)- catalyzed allenylcyclobutanols provide a wide range of bridged bicyclic compounds with a vinyl-substituted quaternary stereogenic center stereoselectively.

The enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven which features metathesis reactions for the rapid assembly of the molecular framework of these antitumor agents is discussed. The application of an Evans Cu-catalyzed aldol addition reaction via a strained cyclopropyl ketenethioacetal and the final RCM/dehydrogenation sequence for the formation of (-)-acylfulvene and (-)-irofulven is also discussed.

Several studies are conducted to explain the development and the synthetic applications of the enantioselective formation of the 1, 1-dicarboxy diesters. The results demonstrate the presence of an excellent trans-d irecting ability in the amide group present in the cycloproponation reactions.

The synthesis of [n,5]-spiroketals (n = 5, 6) via use of exocyclic enol ethers as starting materials is reported. Addition of catalytic amounts of the Lewis acid [Yb(OTf).sub.3] is observed to facilitate the ring enlargement and increase the yield of the corresponding spiroketal in many synthesis examples.

Two approaches to eliminate the generation of unexpected products during the free-radical cyclization process to obtain expected cyclization-reduction products are reported. The secondary cyclization reaction could be avoided by use of a cyclopropylcarbinyl fragmentation and use of an allene as a radical acceptor avoided the atom-transfer reaction altogether.

The preparation of Julia-Kocienski olefination reagents 1-fluoropropyl, (cyclopropyl)fluoromethyl, 1-fluoro-2-methyl-2-propenyl, and 1-fluoro-5-hexenyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfones via metalation followed by electrophilic fluorination is reported. Screening of olefination conditions showed that stereoselectivity which depended on reagent and carbonyl structure could be tuned either toward E- or Z-selectivity.

Lewis acid catalyzed ring opening of 1,1-cyclopropanediesters by the hydroxyl group of a propargyl alcohol sets up a subsequent Conia-ene cyclization to produce substituted tetrahydropyrans in a one-pot, high-yielding procedure.

The cycloadditions of vinylidenecyclopropanes with aldehydes are described for the preparation of tetrahydrofurans. The cycloadditions of vinylidenecyclopropanes with aldehydes and the transformations of the cycloadducts have provided an efficient protocol for constructing various medium- and large-size ring-fused tetrahydrofuran, furan, and benzo[c]fluorene derivatives.

The mechanisms involved in the crossed [2+2] cycloaddition reactions of 1-phenylcyclopropene and 1-bromo-2-phenylcyclopropene are discussed. The various steps and procedures involved in the reactions are also discussed.

Several studies are conducted to explain the various mechanisms that are involved in the switchable reactions of cyclopropanes with enol silyl ethers. The reactions are shown to be extremely useful for the synthesis of substituted cyclopentane derivatives in high yield.

A highly selective convergent coupling reaction between alkynes for the synthesis of stereodefined trisubstituted (E,E)-1,3-dienes-structural motifs commonly found embedded in the skeletons of bioactive polyketide-derived natural products is described. The preparation of complex 1,3-dienes relevant for the synthesis of polyketide-derived natural products of varying stereochemistry with typically [greater than equal to] 20:1 selectivity defined the important role of an alkoxide directing group located [delta] to preformed titanacyclopropenes is also reported.

Several studies are conducted to explain the various mechanisms involved in the synthesis of endo- and exo-configured cyclopropylidenes, which are annelated to the nonbornadiene skeleton. The rearrangement of the carbenes, as well as the impact of the remote substituents on the stability is also discussed.

A practical large-scale chromatography-free synthesis of EP4 antagonist MF-310, a new treatment for chronic inflammation, is described. The key features of the sequence has included a regioselective reduction of succinimide controlled by the electronic properties of a remote pyridine ring, preparation of cyclopropane carboxylic acid via a Corey-Chaykovsky cyclopropanation and a short synthesis of sulfonamide.

The aromatic rings of perfluoro[2.2]paracyclophane are reactive with respect to nucleophilic substitution reactions. The reactions have proceeded via [S.sub.N]Ar mechanisms and the reactivity issues are discussed including the effect of substituents on reactivity and regiochemistry of substitution.

The mechanism of rhodium-catalyzed cyclopropanation and C-H functionalization reactions with methyl phenyldiazoacetate and methyl diazoacetate is computationally studied by using density functional theory (DFT). The analyses of transition state geometries have helped in developing a rational model for predicting the stereochemical outcome of intermolecular C-H insertions with donor/acceptor rhodium carbenoids.

The catalytic activity of heterobimetallic Bi-Rh paddlewheel carboxylate complexes is studied in the context of metal carbenoid chemistry. The Bi-Rh carboxylate complexes have catalyzed cyclopropanation reactions and C-H insertions as well as reactions involving ylide intermediates with similar selectivity profiles to analogous dirhodium complexes.

A highly efficient triflic acid catalyzed ring opening of a wide variety of 1-cyclopropyl-2-propyn-1-ols with alcohols as an efficient synthetic route to conjugated enynes is reported. The mechanism involved protonation of the alcohol substrate by the TfOH catalyst, followed by ionization of the starting material to causes ring opening of the cyclopropane moiety and trapping by the alcohol nucleophile to yield the conjugated enyne product.

The radical clock, intramolecular kinetic isotope effect, and laser flash photolysis (LFP) experiments as well as density functional theory (DFT) and ab initio computations were utilized to study the mechanism of the photochemical [C.sup.2]-[C.sup.6] cyclization of enyne- allenes . The results for enyne-allene provides evidence for an allene triplet excited state (transient A) as a primarily formed short-lived intermediate and the formation of a diphenylmethyl-type diradical resulting from ring opening of a diphenylcyclopropane ring.

Catalyzed by Lewis acid, 1,2-dipehnyldiselane or 1,2-di-p-tolyldisulfane is added to methylenecyclopropanes smoothly. A four-membered carbon ring is constructed to give cyclobutane-1,1-diylbis(phenylselane) derivatives or cyclobutane-1,1-diylbis(p-tolylsulfane) derivatives as products.

Catalyzed by N-heterocyclic carbenes (NHCs), domino ring-opening/redox amidation/cyclization reactions of the formylcyclopropane 1,1-diesters with 2-chloro-1H-indole-3-carboaldehydes are described. This method has provided a direct construction of a 6-5-6-tricyclic hydropyrido[1,2-a]indole skeleton, which is applied for the synthesis of many types of polycyclic indole alkaloids.

1(2-Pyrrolidinyl)cyclopropanecarboxylic acids ([alpha]-cyclopropyl-[beta]-homoprolines) are prepared by 1,3-dipolar cycloadditions of cyclic nitrones onto bicycloproppylidene followed by trifluoroacetic acid induced thermal fragmentive rearrangement. The sterically hindered nitrogen atom of the highly substituted pyrrolidine is acylated through the intermediate formation of a mixed anhydride.

The addition of diazomethane and diazoethane to enantiopure (S)-(+)-3-[(methylphenyl)sulfinyl]-5,6-dihydropyran-2-one has produced the corresponding pyrazolines with almost complete [pi]-facial selectivity. The results are improved starting from sulfonyl pyrazolines, which has produced pure 3-oxabicyclo[4.1.0] heptan-2-ones.

Aryl cyclopropyl ketones have undergone nickel-catalyzed borylative ring opening with bis(pinacolato)diboron to produce 4-oxoalkylboronates.

Pentosyl and hexosyl vinyl sulfone-modified carbohydrates having the terminal double bond and a suitably positioned leaving group are reacted in a stereoselective way with a series of nucleophiles in order to produce a myriad of cyclopropanes substituted at all three ring carbon atoms.

A cascade epoxidation and nucleophilic addition process under mild conditions was used to prepare cyclobutylmethanone and cyclopropylmethanone derivatives in moderate to good yields. The synthesis involved reaction of monoaryl-substituted methylenecyclobutanes (MCBs) and methylenecyclopropanes (MCPs) with 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), and 1-hydroxysuccinimide (HOSu).