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For the mechanism of decarboxylation reactions, all textbooks state that electrons move from the πC=O bond. However, the most electron-donating bond orbital in the carbonyl group is expected to be the lone pair(s) on the oxygen. Thus, orbital theory with delocalization from a lone pair might be more appropriate than delocalization from the πC=O orbital. We confirmed this idea by theoretical calculations. In the transition state of 2-substituted β-keto acids, a boat conformation is expected to result in the exclusive generation of (E)-enols. Normally, the decarboxylation reaction occurs in polar solvents, so the resulting enols should be transformed into the corresponding ketones by tautomerization. The use of heteroatoms to obtain enolate or enol ethers without tautomerization would offer a diastereoselective enol(ate) synthesis with regioselectivity because the C=C double bond would always be introduced between two carbonyl groups. After screening heteroatoms by theoretical calculations, we found that boron is suitable for this purpose. We confirmed our idea by theoretical calculations, offering a new boradecarboxylation reaction for the diastereo- and regioselective production of enolates.

Electrophilic attack to a double bond is often observed anti to the most electron-donating σ-bond at the α-position (hereafter, we refer to this as the extended anomeric effect). This preference is believed to result from the antiperiplanar effect between the bond that is formed between the double bond and the electrophilic reagent, and the donating vicinal σ-bond which is located on the substituent at the α-position. From an orbital viewpoint, however, it is still unclear why the approach of the electrophile anti to the substituent results in stabilization or why the frontier molecular orbital (FMO) deforms, expanding toward the reagent with this antiperiplanar interaction. We demonstrate here that cyclic orbital interaction including geminal bond participation plays an important role in the diastereoselectivity in electrophilic addition. We examined our idea using the electrophilic addition of chlorine to 3-substituted propenes as a model reaction. Our bond model approach should contribute to a better understanding of orbital mixing in FMO.

Recently we reported that 2,6-dithiaspiro[3.3]hepta ne 2,6-dioxide 1a exists as enantiomers at ambient temperature and is able to be resolved. Th is is because the lone pair(s) on the sulfur atom(s) are rich in s-character, which results in h igh barrier for flipping the conformation of the four-membered ring, i.e., racemization of the spiro framework of 1a. During the HPLC analysis, we noticed considerably strong absorption of UV at 210 nm. We expected that the absorbance comes from n-σ* excitation. The acute bond angle of C-S-C leads to high p-character of the C-S bond(s), which lowers the σ* orbital energy. We performed the TD-DFT calculations of a model, constrained dimethylsulfoxide (DMSO) and 1a . The strong UV absorption of 1a is reproduced with the TD-DFT calculation. However, there are two sulfoxide groups arranged with chiral position in 1a , we could expect that the circular dichroism (CD) spectra are observable by coupling of two sulfoxide groups. Th e TD-DFT calculation showed that the Cotton effects should appear in the observable UV r ange. We separated the enantiomers of 1a by HPLC equipped with a chiral stationary phase col umn. The enantiomers are subjected to the CD analysis. We determined the absolute configurat ion of 1a , comparing the calculation and the obtained spectra. This is the first report of the CD spectra of n-σ* excitation.

Recently we have shown that retro-Nazarov reactions are under the control of geminal bond participation. In retro-Nazarov reactions, electrocyclic ring-opening must occur in a conrotatory manner, so that a geminally 4,4-disubstituted substrate and cis -4,5-disubstituted substrate may exhibit the same torquoselectivity with a substituent effect. For amino-hydroxy substituted substrates, however, cis -5-amino-4-hydroxy substituted 9 was calculated preferentially to give E -amino- Z -hydroxy product Z - 12 , while geminally disubstituted 4-amino-4-hydroxy 11 was expected to predominantly afford Z -amino- E -hydroxy product E - 12 . We demonstrate here that this discrepancy in torquoselectivity can be explained in terms of geminal bond participation: in 9 , the most electron-donating σ-bond is σ CH geminal to the amino group, which should rotate inwardly. Thus, the amino group should rotate outward. On the other hand, the σ CN bond is more electron-donating than the σ CO bond, which results in inward rotation of the amino group in 11 .

We have designed a new axially chiral bis(sulfoxide) molecule with conformational rigidity: 2,6-dithiaspiro[3.3]heptane 2,6-dioxide 2a . This molecule has axial asymmetry due to two puckered thietane ring systems. The lone pairs on the sulfur show a strong s-character, which was expected to result in a high barrier to racemization, that is, inversion at the sulfur. We confirmed this prediction by calculations and experimentation. The lone pairs of the sulfur in 2a are sp 1.00 and the enthalpy of activation (Δ H ‡ ) for inversion is 47.5 kcal/mol (B3LYP/6-31G(d)). The 1 H NMR spectra of 2a showed two doublets and two doubled doublet peaks, which resulted from the rigidity of the four-membered ring frameworks without flipping. We separated the enantiomers of 2a by HPLC with a chiral stationary phase column to observe a set of complementary peaks. We also calculated the diselena- and ditellura congeners and confirmed that they also show axial chirality.

Torquoselectivities of electrocyclic ring-opening reactions have been proposed to be controlled by the participation of electron-donating σ-bonds (σ-EDB) geminal to the breaking σ-bond and/or vicinal electron-accepting σ-bonds (σ-EAB) or lone pair(s) of the substituent(s). We designed reactions in which the effects of the vicinal bonds should be significantly diminished by the cationic nature of the reactants. The calculated enthalpies of activation of the retro-Nazarov reactions of some 3-substituted cyclopentenyl cations show inward rotation of the geminal σ-EDB, which is consistent with the theory of geminal bond participation.

The diastereoselectivity of the [3,3]-rearrangement of 1,1-disubsstituted allyl carboxylates was studied. In this heteroatom-containing system, the transition state has a boat-like transition structure (TS) because of the participation of the lone pairs and the secondary orbital interaction. Although the TS for the [1,3]-rearrangement has a far higher barrier, it does not proceed in the usual antarafacial manner due to the cyclic orbital interaction among two lone pairs of the carboxylate and the allylic lumo. In conjunction with the geminal bond participation, delocalization to the σ-bond at the Z-position shows a bonding character in the transition state of the [3,3]-rearrangement. Therefore, we predicted that a more electron-withdrawing σ-bond prefers the Z-position in the product. We designed the 1,1-disubstituted substrates with trimethylsilyl and pentyl groups, and found that the trimethylsilyl group prefers the Z-position despite its steric bulkiness. We confirmed our prediction by experimentation. This Z-selectivity was improved when a trimethylgermyl group was used.

Molecules that contain a double bond between hypervalent atoms were designed. They included monocyclic five-membered ring molecules [HCO2(FPn)2]- and bicyclic molecules [HCO2Pn]2 (Pn = Sb, Bi), whi...

We predicted that uncatalyzed Mukaiyama aldol reactions are under the control of the geminal bond participation. At the transition state of the model reaction, addition of CH 2 O and CH 2 CH(OSiH 3 ), the interbond energy IBE is negative between the σ-bonding orbital at the Z -position of the enolate terminal and π C O ∗ , and positive between that at the E -position and π C O ∗ . These results led us to predict that the electron-donating σ-bond at the Z -position enhances the reactivity. We calculated the enthalpies of activation of the reactions of a variety of the R-substituted silyl enolates and confirmed the prediction by showing that the reactivity of the Z -isomers relative to that of the E -isomers increases with the energy of the bonding orbital of the σ bond at the Z -position (the axial position at the transition state of the chair form). We demonstrate that the geminal bond participation is general not only to the pericyclic reactions but also to the aldol reaction, which is one of the most fundamental C–C bond forming reactions.

Introduction of a double bond into cyclic silanes lowers the ring strain by the cyclic delocalization of π-electrons through the hyperconjugation with the σ bonds, which is favored by the high π-orbital energy of the Si Si bond and the low σ*-orbital energy of the Si–H bonds. The π-relaxation of strains significantly occurs in the small rings. Unsaturated small silicon ring molecules are less strained than the saturated ones and the unsaturated carbon congeners. We calculated a series of polycyclic silicon molecules to confirm the π-relaxation and suggested that some unknown molecules could be prepared due to the low strain.

We applied the geminal bond participation theory to Alder ene reactions. The interaction between the σ-orbital at the Z -position of the double bond of propene and the π ∗ -orbital of ethylene was predicted to be bonding, while that at the E -position should be antibonding. This prediction was confirmed by the bond model analysis of the model compound. These results suggest that the reactivity could be enhanced by substituting a more electron-donating σ-bond at the Z -position. To examine our prediction, theoretical calculations were performed for the systematically substituted substrates. The prediction was confirmed except in the case where the inductive effect of oxygen could affect the reactivity. The same trend in reactivity was observed for formaldehyde as an enophile.

Disilanes bearing four carboxylate ligands have a trigonal bipyramidal geometry around each silicon atom with two bridging carboxylate ligands with the apical Si-O axes, which are parallel to each other, in the crystalline state, while such a structure is in equilibrium with a tetrahedral structure in solution.

We have designed a new axially chiral diphosphine that shows conformational rigidity: 2,6-diphosphaspiro[3.3]heptane 2a . This molecule has axial asymmetry due to puckering of the two phosphetane ring systems. Although its nitrogen congener 2,6-diazaspiro[3.3]heptane 1a is easily racemized, 2,6-diphosphaspiro[3.3]heptane 2a does not racemize at ambient temperature because the lone pairs on the phosphorus atoms have a strong s-character, which results in a high barrier to inversion at the phosphorus, that is, a high barrier to racemization. We also calculated the properties of the diarsa congener 3a and predicted that it also exhibits axial chirality and that it can be separated into enantiomers at ambient temperature.

We showed that imidoyl- and phosphaethenyl(alkali metals) would thermodynamically prefer the Z-configuration. The bond model analysis of the electronic structures showed that the Z-preference should originate from 1,2-metallobridging by the delocalization of lone pairs on N or P to vacant p-orbitals of the alkali metals and from the antiperiplanar effect of the delocalization from σ C—M to σ∗ N(P)—R 2 and from n N(P) to the C—R1. The Z-preference increases by more electron-withdrawing groups at the carbon atom of the double bond. However, substitution at the nitrogen/phosphorus results in E-preference because of 1,4-chelation of the lone pair of the substituents to alkali metals. Most of halogen derivatives were not stable and eliminate metal halides.

We applied the geminal bond participation theory to cheletropic reactions. The interaction between σ-orbital of the inner bond and the π*-orbital of the NN bond was predicted to be bonding, while that involving the outer bond should be antibonding. The difference in the bonding/antibonding character of these interactions is due to the cyclic orbital interaction between the π*-orbital of the NN bond and the geminal bonds at the reaction center, which is influenced by the phase continuity between the orbitals. This prediction was confirmed by the bond model analysis of model compound 1a. These results suggest that reactivity could be enhanced by substituting the inwardly rotating σ-bond by a more electron-donating one, i.e. inward rotation of a substituent with a more electropositive atom. Theoretical calculations were performed for systematically substituted substrates. The prediction was confirmed except in the case of 1g, which was affected by the inductive effect of oxygen. Silyl/methyl-substituted 1e was subjected to the bond model analysis to confirm that the preferred inward rotation of the silyl group of 1e results from the geminal bond participation and little affected by steric effects.

The eclipsed conformers of ClSiH2SiH2SiH2OH (1) and dl -ClSiH2(OH)SiHSiH(OH)SiH2Cl (2) are the most stable due to the attractive 1,4-hypercoordination by the nO and σ*SiCl orbital interaction. The eclipsed rotamer of ClSiH2(OH)2SiSi(OH)(SiH2Cl)2 (3) is the exclusive conformer stabilized by the threefold 1,4-hypercoordination.

Recently, the first heptacoordinate disilane [(MesCS 2 ) 2 MeSi] 2 1 was synthesized and shown to have a unique structure by X-ray analysis. Each of the silicon atoms is surrounded by three nonbonded thiobenzoylthio groups. We theoretically investigated the origins of the unusual geometry of 1 containing multiple hypercoordinations. The model compound [(HCS 2 ) 2 MeSi] 2 2a shows both the H-CSi-Si eclipsed conformation and the C-SiSi-C eclipsed conformation. The dihedral angle of H-CSi-Si is calculated to be 24.6° at the RHF/6-31G* level (25.7° at the RHF/LANL2DZ+p level). Each of the carbon atoms of the methyl groups is also surrounded by three nonbonded thioformylthio groups. After the bond model analyses, we found that hypercoordination to the saturated carbon atom is essential for this unique geometry, as confirmed by scrutinizing the X-ray data of 1 .

Ring strains are relaxed by the cyclic orbital interaction between a π-bond and the σ-bonds on the saturated atoms in the rings. An effective relaxation by the π–σ* interaction occurs in the three-, four-, and five-membered silicon rings. Cyclotrisilene 2b , cyclotetrasilene 4b , and cyclopentasilene 6b have lower strains than those of the parent saturated analogs. However, the stabilization is less significant for the hydrocarbons.

Structures and reactions of CH3OCH2M (M = Li, Na, K) were investigated in a theoretical manner. CH3OCH2M has the acute bond angle of ∠M-C-O due to a strong coordination of the oxygen to the alkali metals. The nucleophilic substitution reaction of the substrate CH3OCH2Li by the nucleophile CH3OCH2Li is more preferred than the carbene generation by α-elimination and a nucleophilic substitution of CH3OCH2Li by CH3Li. The resulting 2-methoxyethyllithium readily liberated lithium methoxide to afford ethylene, which added to the anion species to give an ethylated product. Among the CH3OCH2M (M = Li, Na, K), CH3OCH2K is the most nucleophilic, due to the high σC–K level, while CH3OCH2Li is the most nucleophilic because of the lowest σ*C–O level. This supports a previously proposed mechanism for the ethylation of indole derivatives by methyl ethers in the presence of BuLi - t-BuOK.

Complexation of dimethyl penta-2,3-dienedioates to tris[(R)-(1R*)-3-(2,2,3,3,4,4,4-heptafluoro-1-oxobutyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-onato-O,O‘]europium, (+)-Eu(hfc)3, enriched the (S)-isomer with high enantioselectivity. When a more bulky ester was used, although the enantioselectivity increased to >95% ee, considerable decomposition occurred. Among the available lanthanide shift reagents, only the europium reagent is effective in this transformation. The reaction involves interconversion of diastereomeric complexes, with enrichment of the preferred one. However, the observed decrease in the 1H NMR peaks might suggest that subsequent reconstruction or reordering the higher-order complex may occur in the reaction solution.

Stereospecific annulation of hydroxy vinyl ethers in the presence of triflic anhydride and tertiary amines and its synthetic application are described. Each 1-hydroxy-2-oxabicyclo[n.4.0]alkane, 2-oxabicyclo[n.4.0]alk-1(6)-ene and 2-oxabicyclo[n.4.0]alk-1(6+n)-ene is stereoselectively synthesized from the same hydroxy vinyl ether depending on the choice of the reaction conditions (temperature, solvent and tertiaryamine). These compounds lead to polyfunctionalized cyclic compounds and some natural products. We propose that this annulation reaction proceeds through a pure SN2-like mechanism.

An efficient and stereospecific ring formation from unsaturated alcohols, which in turn are prepared by regio- and stereospecific ring opening of acetals, is described

A novel method for the highly regioselective deprotonation of the indole alkyl substituents has been established by the particular sequence of base treatments. This success may be due to the aromatic stabilization of cross [6e/4p] conjugated systems. We are presently pursuing further application revolving around this methodology

Stereospecific annulation of hydroxy vinyl ethers in the presence of triflic anhydride and tertiary amines and its synthetic application are described. Each 1-hydroxy-2-oxabicyclo[n.4.0]alkane, 2-oxabicyclo[n.4.0]alk-1(6)-ene and 2-oxabicyclo[n.4.0]alk-1(6+n)-ene is stereoselectively synthesized from the same hydroxy vinyl ether depending on the choice of the reaction conditions (temperature, solvent and tertiaryamine). These compounds lead to polyfunctionalized cyclic compounds and some natural products. We propose that this annulation reaction proceeds through a pure SN2-like mechanism.

Highly enantioselective deracemization route of chiral 2,3-pentadienedioates was achieved by complexation with the chiral organoeuropium reagent.

Analysis characteristics of the hydrogen isotopes H 2 , HD, HT, D 2 , DT and T 2 were experimentally studied using gas chromatography. A liquid nitrogen cooling column was employed for isotope separation, along with a thermal conductivity detector and a small-volume ionization chamber. The intensity ratio of the six hydrogen isotopes as measured by the thermal conductivity detection was H 2 :HD:HT:D 2 :DT:T 2 = 100:73:61:57:49:43. When the sampling volume was 1 cm 3 , the estimated detection limits for H 2 and T 2 were, respectively, 20 and 50 Pa partial pressure and 200 and 500 ppm concentration. The 0.16-cm 3 ionization chamber could measure only the tritiated molecules, and the estimated detection limit for T 2 gas was 1 ppm. The retention time was reduced when the concentration was greater than 1%. In particular, when it was increased above 10%, identification of neighboring peaks tended to be difficult.

1-Oxa-2,3-cyclohexadiene (I) can be readily generated by treatment of 5-bromo-3,4-dihydro-2H-pyran with potassium tert-butoxide in the presence of 18-crown-6 and can be trapped with dienes or olefins. Thus, the treatment of I with furan gave 50% yield of Diels-Alder adduct II, whereas with 1,1-diphenylethylene I gave 43% of the [2+2]cycloadduct III. The remarkable regio- and stereoselectivities with which [4+2] and [2+2] adducts are formed suggests a concerted, non-radical cycloaddn. mechanism. [on SciFinder (R)]

We apply an orbital phase theory to the torquoselectivity of the electrocyclic reactions of 3-substituted (X) cyclobutenes. The torquoselectivity is shown to be controlled by the orbital-phase relation of the reacting pi(CC) and sigma(CC) bonds with the sigma(CX) bond geminal to the sigma(CC) bond to be cleaved. The inward rotation of electron-donating sigma(CX) bonds and outward rotation of electron-withdrawing sigma(CX) bonds have been deduced from the orbital-phase theory. Enhancement of the inward rotation by the electron-donating capability of the sigma(CX) bonds is confirmed by the correlation between the torquoselectivity and sigma(CX) orbital energy. The orbital overlaps between the geminal sigma(CX) (sigma(CH)) and sigma(CC) bonds are found to be important as well. Unsaturated substituents with low-lying unoccupied pi orbitals also promote the inward rotation.

A novel method for the highly regioselective deprotonation of the indole alkyl substituents has been established by the particular sequence of base treatments. This success may be due to the aromatic stabilization of cross [6e/4p] conjugated systems. We are presently pursuing further application revolving around this methodology

An efficient and stereospecific ring formation from unsaturated alcohols, which in turn are prepared by regio- and stereospecific ring opening of acetals, is described

The use of chiral organoaluminum reagent as a catalyst to resolve simple ketoepoxides is explored. The optically pure ketoepoxide 10 was recovered after 80% conversion. The recovered pure epoxide is a useful chiral building block in the synthesis of chiral terpenes. The method applies for the short asymmetric synthesis of the juvenile hormone by the synthetic route which depends on the palladium-catalyzed coupling process.

Employing the homochiral acetal template, asymmetrization of meso-substituted cyclohexanones is explored. By the use of optically-active 2,4-pentanediol as a chiral protecting group, highly diastereoselective acetal cleavage is achieved when treated with organoaluminum reagent. Dialkylaluminum amides are also effective reagents for this reaction.

This paper will review the current state-of-art of organoaluminum- or organoboron-mediated asymmetric reactions in the natural product synthesis. The newly developed methods heavily depend on the characteristic features of main group organometallic compounds. Asymmetric Diels-Alder reaction, pioneered by Walborsky (ref. l), has been established as one of the most important tools in modern synthesis of natural products. In the study of the influence of concave-convex topological features on asymmetric Diels-Alder reactions, a number of fascinating chiral auxiliary groups were reported (ref. 2). However, readily available dimen- thy1 fumarate appears to deserve careful reinvestigations since its primitive topological feature seems to be underestimated. Thus, the Lewis acid coordinated fumarate is considered to exist in the s-trans form predominantly and the two menthyl groups should cooperatively cover the re face of the molecule. A series of dienes was then subjected to Diels-Alder reaction with or- ganoaluminum reagent at low temperature and all the attempted reaction proceeded with excel- lent stereoselection (ref. 3).

A short synthetic route to C 16 -juvenile hormone is described which depends on new oxirane ring opening methodology and which also involves the joining of intermediate 8 and 12 in a one flask operation to construct the sesquiterpene structure.

A method is described for regioselective monoprotection of 1,n-diols. The new process depends on regioselective cleavage of orthoester, which is prepared in situ from 1,n-diols and trialkylorthoesters. The produced mono-acetal is useful in subsequent steps as a normal acetal type protecting group.

A new synthetic procedure for the practical synthesis of β-trimethylsiloxyketones from silyl enol ethers and aldehydes has been described which heavily depends on organoaluminum reagent as an effective catalyst.

A new synthetic procedure for the practical synthesis of β-trimethylsiloxyketones from silyl enol ethers and aldehydes has been described which heavily depends on organoaluminum reagent as an effective catalyst.