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The synthesis of a series of conformationally locked mannopyranosyl thioglycosides in which the C6-O6 bond adopts either the gauche,gauche, gauche,trans, or trans,gauche conformation is described, and their influence on glycosylation stereoselectivity investigated. Two 4,6-O-benzylidene-protected mannosyl thioglycosides carrying axial or equatorial methyl groups at the 6-position were also synthesized and the selectivity of their glycosylation reactions studied to enable a distinction to be made between steric and stereoelectronic effects. The presence of an axial methoxy group at C6 in the bicyclic donor results in a decreased preference for formation of the β-mannoside, whereas an axial methyl group has little effect on selectivity. The result is rationalized in terms of through-space stabilization of a transient intermediate oxocarbenium ion by the axial methoxy group resulting in a higher degree of SN 1-like character in the glycosylation reaction. Comparisons are made with literature examples and exceptions are discussed in terms of pervading steric effects layered on top of the basic stereoelectronic effect.

The combination of experiments and computations reveals unusual features of stereoselective Rh(I)-catalyzed transformation of propargyl vinyl ethers into (E,Z)-dienals. The first step, the conversion of propargyl vinyl ethers into allene aldehydes, proceeds under homogeneous conditions via a “cyclization-mediated” mechanism initiated by Rh(I) coordination at the alkyne. This path agrees well with the small experimental effects of substituents on the carbinol carbon. The key feature revealed by the computational study is the stereoelectronic effect of the ligand arrangement at the catalytic center. The rearrangement barriers significantly decrease due to the greater transfer of electron density from the catalytic metal center to the CO ligand oriented trans to the alkyne. This effect increases electrophilicity of the metal and lowers the calculated barriers by 9.0 kcal/mol. Subsequent evolution of the catalyst leads to the in situ formation of Rh(I) nanoclusters that catalyze stereoselective tautomerizatio...

The crystal structures of three 2-amino-1,3-oxazolidin-4-one derivatives are reported. 5,5-Dimethyl-2-dimethylamino-3-phenyloxazolidin-4-one crystallizes in the space group P21,/c with a= 15.540(3), b= 7.016(2), c= 12.491(4)A, β= 105.6(2)° 1 342 reflections with I 2.5 σ(I) were used in the refinement. 4-Benzyl-2,2-dimethyl-1-oxa-4,6-diazaspiro[4,5]decan-3-one crystallizes in the space group P21/c with a= 15.188(6), b= 12.074(2), c= 8.468(1)A, β= 100.03(2)° 2 068 reflections with I 3σ(I) were -used in the refinement. 4-Benzyl-2,2-dimethyl-1-oxa-4,6-diazaspiro[4,6]undecan-3-one crystallizes in the space group P21,/c with a= 9.460(5), b= 20.192(6), c= 9.012(3)A, β= 110.66(4)° 1 873 reflections with I 3σ(I) were used in the refinement. The analysis of bond distances of the three structure has shown that exo-cylic C–N bonds (exo with respect to the oxazolidinone ring) are significantly shorter than the standard C(sp3)–N(sp3) distance by 0.050 A on average. This could be the main factor determining the stability of the three cyclic orthoester aminals, the stabilization being attributable to an exo-anomeric effect involving the interaction between the nitrogen sp3-like lone pair, in an antiperiplanar orientation, and the σ*orbital of the endo C–O bond.

The mechanism we propose for the cyclopentane annulation is the following one. The allylic reagent (5D) attacks the siloxypyrylium salts (2a,b) at the C2 position, giving the intermediate carbocation (B) which is stabilized by the trimethylsilyl and the methyl group. Attack by the emerging enolate at C 3 , forms the five-membered ring compound (8a,b). Generally, electrophiles attack allylic silanes anti to the silyl group. Since there is undoubtedly interaction with the silicon in the transition state, the stereochemistry of the bridged intermediate (B) should be trans geometry due to stereoelectronic effect and allylic 1,3-strain. In the reaction of 2a, the favored pathway is cyclization. However, competition between cyclization and desilylation was observed in 2b due to steric hindrance between the two methyl groups at the step of cyclization

Two diastereoisomeric phenylselenoesters of 4,5-dihydroxyhept-6-enoic acid were prepared as their acetonide derivatives from the chiral pool. On treatment with tributyltin hydride and azoisobutyronitrile the erythro isomer cyclized to give meso-4,5-dihydroxycycloheptanone, as its acetonide, in moderate yield whereas under the same conditions the threo-isomer gave a much lower yield of the corresponding C2-symmetric ketone. In the erythro-series an alkyl group at C-7 of the heptenoyl system was found to retard significantly the direct endo-mode cyclisation; however, the cycloheptanone could still be obtained by a rearrangement when the tin hydride concentration was kept to a minimum. A tandem 7-endo/5-exo cyclization system was then constructed and tested, resulting in the formation of all four possible diastereoisomeric bicyclo[5.3.0]decanones. Further model studies were conducted on the effect of alkyl and alkoxy substituents at C-5 of the heptenoyl radical system on the mode of cyclisation. Alkyl substituents exert a steric effect whilst alkoxy substituents also have a stereoelectronic effect.

The isopropyl group has no significant Stereoelectronic effect on inter- and intra-molecular competition in deprotonation from alkylbenzene radical cations in the photoaddition of alkylbenzene derivatives with 10-methylacridinium ion viaphotoinduced electron transfer from alkylbenzene derivatives to the singlet excited state of 10-methylacridinium ion, followed by the deprotonation of alkylbenzene radical cations.

Hydroxide-dependent hydrolysis of triesters of phosphonoformic acid (PFA)via P–O bond cleavage proceeds at rates 103–106 times greater than hydrolysis of simple phosphonates. The means by which an α-carbonyl substituent elicits such a rate enhancement has been examined using ab initio calculations. Model compounds have been derived, from full geometry optimization at the RHF/6-31G*//6-31G* level, of (a) the tetracoordinate ground state PFA triesters (4, RPO3Me2; R = CHO) and simple phosphonate esters (4, R = CF2H, CH3), and (b) pentacoordinate intermediates for hydrolysis of these triesters (5, RPO4H3–; 6, RPO4HMe2–, R = CHO, CO2H and 5, 6, R = CF2H, CH3, respectively). Intramolecular charge-transfer interactions have been quantified employing natural bond orbital analysis, including calculation of molecular energies on deletion of each individual interaction. These molecular orbital calculations demonstrate significant stabilizing, intra-molecular charge-transfer interactions, including internal hydrogen bonding and np(O)→π*(CO) charge transfer in the pentacoordinate state. The n→π* stabilization contributes 4–10 kcal mol–1 to the stabilization of these intermediates in the gas phase. It is suggested that such charge-transfer stabilization in the pentacoordinate intermediates and transition states for hydrolysis of PFA triesters contributes to the observed rate enhancement. In contrast, these calculations show no evidence for the stereoelectronic effect (akin to the generalized anomeric effect) proposed by Gorenstein and Taira for pentacoordinate phosphoranes and suggested also to lead to large rate enhancements for nucleophilic substitution at phosphorus. Calculations on models [7, RC(O)CO3HMe–, R = H, OH] for tetrahedral intermediates in oxalate ester hydrolysis demonstrate a greatly diminished intramolecular np(O)→π*(CO) charge-transfer stabilization. This is in accord with rate data on carboxylate ester hydrolysis.

Catalytic hydrogenation of the title compound proceeds from the site anti to the 7-methyl group to give the cis-dimethyl derivative; a possible stereoelectronic effect accounting for this selectivity is proposed based on the conformational analysis of the substrate by X-ray crystallography.

Diastereoselective alkylation of enolate dianion of ( S )-4-carboethoxymethyl-2-oxazolidinone has been studied. The increased anti -selectivity in the presence of HMPA was explained by stereoelectronic effect of the electron-rich nitrogen atom of the oxazolidinone amidate.

Regioselective bond scission of cyclopropyl ketones 1a-d in single electron transfer (SET) reductive process with tributytin hydride has been found to be controlled by radical stabilizing effect. In the case of 1e and 11 stereoelectronic effect was also operative. Under photoinduced electron transfer (PET) condition similar regioselectivity was also observed. A ring expansion product 16 via intramolecular ketone-cyclopropane interaction was obtained from 1b in this case.

The alkylation of 4-hydroxyproline derivatives 7 and 1 2 with a range of alkylating reagents was examined. The stereoselectivity was found to be dependent on the reagent and the N-protecting group. This was explained by a concept based on the stereoelectronic effect and π-interaction.

A convenient new method was developed to prepare two types of vinyl cyclopropane derivatives through gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonates 2. Different from the previous reported 5-exo-dig route, the 6-endo-dig addition is the preferred pathway to provide six-membered cyclized carbonates. Two factors, including stereoelectronic effect and steric effect might affect the regioselectivity. Therefore, low steric aliphatic substrates afforded only six-membered isomers. The synthetic utility of compound 3 was also explored to afford a series of β-carbonyl cyclopropanol derivatives.

The catalytic asymmetric intermolecular Stetter reaction of heterocyclic aldehydes and nitroalkenes has been developed. We have identified a strong stereoelectronic effect on catalyst structure when a fluorine substituent is placed in the backbone. X-ray structure analysis provides evidence that hyperconjugative effects are responsible for a change in conformation in the azolium precatalyst. This new N-heterocyclic carbene precursor bearing fluorine substitution in the backbone results in significantly improved enantioselectivities across a range of substrates.

A systematic study of C-H insertion reactions with variously substituted and conformationally constrained substrates was carried out. High selectivity in the insertion between two competing C-H bonds caused by a strong stereoelectronic effect of an oxygen substituent was achieved. This regioselective C-H insertion reaction was employed as a platform to develop a concise asymmetric synthesis of platensimycin.

Anomeric O-alkylation/arylation is applied to the synthesis of 2-deoxy-β-glycosides. Treatment of lactols with NaH in dioxane followed by the addition of electrophiles leads to the formation of 2-deoxy-β-glycosides in high yield and high selectivity. The high β-selectivity observed here demonstrates a powerful stereoelectronic effect for the stereoselective formation of acetals under kinetic control.

The influences of the modifications of the natural nucleotides is rationalized in terms of stereoelectronics effects. This article reviews the pseudorotation concept and the Generalized Karplus Type equation used to quantify the conformational behavior of ribofuranose in solution.

The total syntheses of three drimane-type sesquiterpenoids, (–)-mniopetal E, (–)-mniopetal F, and (–)-kuehneromycin A, are described. These natural products inhibit the enzymatic activity of RNA-directed DNA-polymerases (reverse transcriptases) of the human immunodeficiency virus (HIV)-1. Our enantiospecific total syntheses of these target molecules in naturally occurring forms commenced with a known 2,3-anhydro- d -arabinitol derivative, which was prepared using the Sharpless asymmetric epoxidation strategy. A combination of highly stereocontrolled inter- and intramolecular Horner–Emmons carbon elongations led to the two butenolides tethering 1,2,4,9- and 1,4,9-functionalized nona-5,7-diene moieties at the β-carbon. The key step in mniopetal E synthesis is a stereoselective thermal intramolecular Diels–Alder reaction of the former butenolide compound, providing a highly oxygenated tricyclic skeleton with the desired endo and π-facial selections. The intramolecular Diels–Alder reaction of the latter butenolide compound for the syntheses of other two drimanes also proceeded with the desired stereoselectivity, which is controlled by a balance of the steric effect and the stereoelectronic effect of a trialkylsilyloxy substituent existing adjacent to the dienophile in accordance with Cieplak’s theory. The transformation of the γ-lactone moiety in the cycloadducts to the γ-hydroxy-γ-lactone part was efficiently achieved via a tetracyclic intermediate. Our total syntheses of (–)-mniopetal E, (–)-mniopetal F, and (–)-kuehneromycin A established the unsettled absolute stereochemistries of the antibiotics. In addition, the reported total syntheses by Jauch are briefly reviewed.

A series of 4‐substituted Hantzsch 1,4‐dihydropyridines has been synthesized. Substituents at the 4‐position include 2‐pyridyl, 2‐imidazolyl, and 1‐methyl‐2‐imidazolyl. By use of various acetoacetic ester derivatives methoxy and methylthio groups have been introduced in the ester side chains at the 3,5‐positions. A representative example is bis(2‐methoxyethyl) 1,4‐dihydro‐2,6‐dimethyl‐4‐(1H ‐imidazol‐2‐yl)‐3,5‐pyridinedicarboxylate (5h ). The crystal structure of bis‐[(2‐methylthio)ethyl] 1,4‐dihydro‐2,6‐dimethyl‐4‐(1H ‐imidazol‐2‐yl)‐3,5‐pyridinedicarboxylate (5i ) has been determined. The imidazole group at the 4‐position is located in a pseudo‐axial position. In the 13C‐ and 1H‐NMR spectra line doubling is seen in the 4‐imidazole‐substituted derivatives. This is apparently the result of slow tautomerization. Various complexes with Zn(NO3)2 · 4H2O have been prepared but no crystal structures could be obtained. These 1,4‐dihydropyridines have little capacity, either in the presence or absence of metal ions, to carry out reductions. This may be the result of a stereoelectronic effect caused by the (presumably) equatorial orientation of the hydrogen (hydride) to be donated.

The preparation and acid catalysed hydrolysis of a number of isoxazolinyldioxepins is reported. Individual diastereoisomer pairs were isolated by column chromatography and shown to differ significantly in their hydrolytic stability at acidic pH. The crystal structures of one diastereoisomer pair reveal that conformational differences induce a selective stereoelectronic effect at the acetal centre of the more hydrolytically labile isomer, while the less labile isomer shows no such selectivity.