Alkaloid studies. VI. lithium aluminum hydride reduction of apoyohimbine and the synthesis of 3,4,5,6-tetradehydroyohimbane-16-methanols

Catalytic reduction of apoyohimbine ( 1 ), prepared from yohimbine and thionyl chloride in pyridine, gives methyl yohimbane-16α-carboxylate ( 2 ) after equilibration with methoxide. LAH reduction of 2 or β-yohimbine O-tosylate ( 3 ) gives yohimbane-16α-methanol ( 4a ). LAH reduction of 1 affords yohimbane-16α-carboxaldehyde ( 5 ), yohimb-16-ene-16-methanol ( 6a ) and yohimbane-16β-methanol ( 7a ). Structural assignments 6a and 7a are confirmed by mass spectral measurements. Pmr spectra of 4a, 6a and 7a and their O-acetates 4b, 6b and 7b are discussed. LAH reduction of apo-α-yohimbine ( 8 ) affords alloyohimb-16-ene-16-methanol ( 9 ). Dehydrogenation of 4a with palladium black and maleic acid gives 3,5,4,5,6-tetradehydroyohimbane-16α-methanol ( 10 ) iodide, and 7a gives 3,4,5,6-tetradehydroyohimbane-16β-methanol ( 11 ) iodide and picrate. Properties of 10 and 11 differ from those of melinonine E.     

Polyfluoro-1,2-epoxy alkanes and cycloalkanes. Part IV [1]. Thermal reactions of the epoxides of the pentamer and hexamer oligomers of tetrafluoroethene

Oxirans (1) and (2), derived respectively from the pentamer and hexamer oligomers of tetrafluoroethene, were pyrolysed over pyrex glass at 300–500° alone and in the presence of cyclohexene, bromine and toluene. Thus, oxiran (1), pyrolysed alone, afforded perfluoro-2-methylbut-1-ene (3), perfluoro-2,3-dimethylpent-2-ene (4) and (E) and (Z) perfluoro-2,3-hex-3-ene (TFE tetramer) (5a, 5b). Co-pyrolysis of (1) with bromine afforded (E) and (Z) 2-bromoperfluoro-3-methylpent-2-ene (6a, 6b), whilst with toluene, (E) and (Z) 2H-perfluoro-3-methylpent-2-ene (7a, 7b) were obtained: (1) with excess cyclohexene also gave (7a, 7b). The oxiran (2), on pyrolysis alone, gave only (3). In the presence of bromine, (2) gave an equimolar mixture of 1-bromoperfluoro-3-methylpentan-2-one (8) and 3-bromoperfluoro-3-methylpentane (9). Co-pyrolysis of (2) with toluene yielded (3) and 3H-perfluoro-3-methylpentane (10). Pyrolysis of (2) with cyclohexene at 175° gave perfluoro-3-methyl-2-(1-methylpropyl)pent-2-en-1-oylfluoride (11), pentafluoroethylcyclohexane (12) and perfluoro[(1-ethyl-1-methylpropyl) (1-methylpropyl)]ketne (13).     

An efficient synthesis of 4-(phenylsulfonyl)-4H-furo[3,4-b]indoles

The fused heterocycle 4-(phenylsulfonyl)-4H-furo[3,4-b]indole, which is an indole-2,3-quinodimethane synthetic analogue, is prepared in five steps from indole in 46% yield. A similar sequence is used to synthesize C-3 derivatives (3-methyl, 3-phenyl, and 3-heptyl). Thus, indole-3-carbaldehyde (1) is protected as the N-phenylsulfonyl derivative 2 and converted to the ethylene acetal 6. Lithiation at C-2 followed by treatment with an aldehyde affords the expected hydroxy acetals 7 and 8. Exposure to acid effects cyclization to the furoindoles 5 and 9. Furthermore, C-1 lithiation of furo[3,4-b]indole 9c followed by treatment with methyl iodide affords disubstituted furo[3,4-b]indole 10.     

硫杂冠醚的合成

冠醚化合物对金属离子的络合不仅具有较高的稳定性,而且更重要的是具有良好的选择性。当冠醚环中的氧原子部分或全部被氮或硫原子取代后,它们对碱金属、碱土金属的亲和性能降低,而对过渡金属离子的亲和能力相应提高。硫杂冠醚对亲硫的贵金属、重金属离子具有更强的络合能力和更高的选择性。1974     

Electronically Mediated Selectivity in Ring Opening of 1-Azirines. The 3-X Mode: Convenient Route to 3-Oxazolines

The mild base-promoted reaction of methyl 2-phenyl-1-azirine-3-acetate (1) with aldehydes and acetone provides a new and simple route to the 3-oxazolines 5, which are formed in good yields by the electrophilic trapping of an imino anion produced by C-N bond cleavage in the 1-azirine enolate intermediate 6. Chloranil oxidation of 5 containing an aromatic substituent at C-2 affords oxazoles 7, while reaction of 5 containing an aliphatic group at C-2 produces 5-methylene-3-oxazolines 8 and 5-spiro-2-oxazolines 9 in addition to 7.     

The reactions of tetrafluoroethylene oligomers: V. The reactions of perfluoro-3,4-dimethyl-4-ethylhexene-(2) with thionucleophiles and the chemical transformations of reaction products

The reactions of perfluoro-3,4-dimethyl-4-ethylhexene-(2) (1) with s-nucleophiles such as benzylthiol, allylthiol, phenylthiol and the chemical transformations of these reaction products were reported. 1 reacted with S-nucleophiles to give four types of isomeric products. At ?30～ ?60°C, in ether, kinetically controlled product 2 (a, b, c) were formed. Compound 2 might be converted directly into the thermodynamically stable products 3 (a, b,) in DMF-KF at r.t., At 100°C, 2 was converted to 4 (a, b, c) via intramolecular rearrangement. In KF-DMF at r.t., 4 was isomerized to 5 (a, b, c). 2a also reacted with another mole of thiol to give the corresponding disulfide 6 and hydrogen-containing olefin 7a as well as the disubstituted product 8a in DMF, but only give 3a and 9a in ether-Et₃N. The reaction of 2a with methyl alcohol gave only a small amounts of 3a and 10a. The reaction of 2b with dimethylamine was complex and 3b and 11 were obtained in low yield.     

Inokosterone, an insect metamorphosing substance from Achyranthes fauriei : Absolute configuration and synthesis

Inokosterone, a phytoecdysone isolated from Achyranthes fauriei (Amaranthaceae), has been partially acetylated to give the 2,26-diacetate (4) which has been converted into methyl 5 - acetoxy - 4 - methylpentanoate (7), showing no apparent []_D, and 2β - acetoxy - 3β,14 - dihydroxy - 5β - pregn - 7 - ene - 6,20 - dione (8). Chemical and physiochemical studies have shown the configurations at C-20 and C-22 to be R. Inokosterone has thus been concluded to be a mixture of C-25 epimers of (20R,22R) - 2β,3β,14,20,22,26 - hexahydroxy - 5β - cholest - 7 - en - 6 - one (1). After the synthesis of the model compound, a C-25 epimeric mixture of (20R,22R) - 3β,20,22,26 - tetrahydroxy - 5 - cholestane (23), inokosterone has been synthesized via (20R) - 2β,3β,14,20 - tetrahydroxy - 20 - formyl - 5β - pregn - 7 - en - 6 - one (25) by Grignard reaction with 4 - (tetrahydrofuran - 2 - yloxy) - 3 - methylbutynylmagnesium bromide (15) followed by hydrogenation and hydrolysis. The use of an NMR shift reagent with the inokosterone acetates (9, 29) and the optical activity measurement of - methylglutaric acid (3) derived from inokosterone have established that inokosterone is a 1:2 mixture of the C-25 R and S epimers.     

Studies of some monocyclic and bicyclic arylacetonitriles

The high-resolution (1)H, (13)C, (1)H-(1)H COSY and (1)H-(13)C COSY NMR spectra have been recorded in CDCl(3) for arylacetonitriles 1-12 and analyzed. The arylacetonitriles 3-7 exist in two isomeric forms E (methyl group is anti to cyano group) and Z (the methyl group is syn to cyano group) in solution. Normal chair conformation with equatorial orientations of phenyl rings at C-2 and C-6 for monocyclic nitriles 1 and 2, epimeric chair structure EC (axial configuration of methyl group at C-3) for both the E and Z isomers of arylacetonitrile derivatives (3-7) and a distorted boat form, B(3), for the N-acylacetonitrile derivatives (8-10) have been proposed based on NMR data. The bicyclic nitriles 11 and 12 exist in twin chair conformations in solution. DFT calculations and chemical shifts also support these conformations. Geometry optimizations for 1-12 were carried out according to density functional theory using B3LYP/6-31G(d,p) basis set and for 1 and 8 the theoretical geometrical parameters have been compared with those of single crystal measurements.     

P(CH(3)NCH(2)CH(2))(3)N as a dehydrobromination reagent: synthesis of vitamin A derivatives revisited.

Although P(CH(3)NCH(2)CH(2))(3)N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU. A (31)P NMR study of this reaction suggests that the carbanion generated from acetonitrile-d(3) in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HC triple bond C(CH(3))=CHCH(2)OH to the carbonyl group of (E)-2-methyl-4-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-3-butenal (2) was only moderate (20%), and (9R,10S)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH(4) reduction of the C triple bond C bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr(3) occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.     

Six new dammarane-type triterpene saponins from the leaves of Panax ginseng

Six new minor saponins, together with known ginsenosides, were isolated from the leaves of Panax ginseng. The new saponins were named as ginsenoside-Rh5, -Rh6, -Rh7 -Rh8, -Rh9 and -Rg7, and their structures were elucidated on the basis of chemical and physicochemical evidence to be as follows: ginsenoside-Rh5: 3beta,6alpha,12beta,24zeta-tetrahydroxy-dammar-20(22),25-diene 6-O-beta-D-glucopyranoside (1), -Rh6: 3beta,6alpha12beta,20(S)-tetrahydroxy-25-hydroperoxy-dammar-23-ene 20-O-beta-D-glucopyranoside (2), -Rh7: 3beta,7beta,12beta,20(S)-tetrahydroxy-dammar-5,24-diene 20-O-beta-D-glucopyranoside (3), -Rh8: 3beta,6alpha,20(S)-trihydroxy-dammar-24-ene-12-one 20-O-beta-D-glucopyranoside (4), -Rh9: 3beta,6alpha,20(S)-trihydroxy-12beta,23-epoxy-dammar-24-ene 20-O-beta-D-glucopyranoside (5) and -Rg7: 3-O-beta-D-glucopyranosyl 3beta,12beta,20(S),24(R)-tetrahydroxy-dammar-25-ene 20-O-beta-D-glucopyranoside (6).     

Approaches to 1H-Cyclopropa[l]phenanthrenes. Eliminations with 1a,9b-Dihydro-1H-cyclopropa[l]phenanthrene Derivatives

Base-induced elimination of the sulfonium salt 2i in the presence of furan affords the addition products 7 and 8 , derived from 1H-cyclopropa[l]phenanthrene ( 1 ) and the isomeric cyclopropene 5a (Scheme 3). Upon oxidation, the selenide 2c yields phenanthrene-9-methanol ( 9 ), presumably via 1 . No evidence for the intermediate 1 is obtained from sulfoxide pyrolysis with 2e , which leads to products formed by radical pathways (Scheme 5). Reductive elimination of the disulfone 3b gives half-reduction to monosulfone 2g and complete reduction to cyclopropane 2 as well as 9-methylphenanthrene ( 15 ), but no evidence for the intermediate 1 .     

N-aminopyrroledione-hydrazonoketene-pyrazolium oxide-pyrazolone rearrangements and pyrazolone tautomerism

Flash vacuum thermolysis (FVT) of 1-(dimethylamino)pyrrole-2,3-diones 5 causes extrusion of CO with formation of transient hydrazonoketenes 7. The transient ketenes 7 are observable in the form of weak bands at 2130 (7a) or 2115 cm-1 (7b) in the Ar matrix IR spectra resulting from either FVT or photolysis of either 5 or 1,1-dimethylpyrazolium-5-oxides 8, and these absorptions are in excellent agreement with B3LYP/6-31G* frequency calculations. Under FVT conditions the ketenes 7 cyclize to pyrazolium oxides 8, which undergo 1,4-migration of a methyl group to yield 1,4-dimethyl-3-phenylpyrazole-5(4H)-one 9a and 1,4,4-trimethyl-3- phenylpyrazole-5(4H)-one 9b. All three tautomers of 9a have been characterized, viz. the CH form 9a (most stable form in the gas phase, the solid state and solvents of low polarity), the OH form 9a' (metastable solid at room temperature) and the NH form 9a" (stable in aprotic dipolar solvents). The isomeric 1,4-dimethyl-5-phenylpyrazole-3(2H)- one 12 tautomerizes to the 3-hydroxypyrazole 12'. The crystal structure of the hydrochloride 14 of 9a'/9a" is reported, representing the first structurally characterised example of a protonated 5-hydroxypyrazole.     

Thermal activation of hydrocarbon C-H bonds by tungsten alkylidene complexes.

Thermal activation of CpW(NO)(CH(2)CMe(3))(2) (1) in neat hydrocarbon solutions transiently generates the neopentylidene complex, CpW(NO)(=CHCMe(3)) (A), which subsequently activates solvent C-H bonds. For example, the thermolysis of 1 in tetramethylsilane and perdeuteriotetramethylsilane results in the clean formation of CpW(NO)(CH(2)CMe(3))(CH(2)SiMe(3)) (2) and CpW(NO)(CHDCMe(3))[CD(2)Si(CD(3))(3)] (2-d(12)), respectively, in virtually quantitative yields. The neopentylidene intermediate A can be trapped by PMe(3) to obtain CpW(NO)(=CHCMe(3))(PMe(3)) in two isomeric forms (4a-b), and in benzene, 1 cleanly forms the phenyl complex CpW(NO)(CH(2)CMe(3))(C(6)H(5)) (5). Kinetic and mechanistic studies indicate that the C-H activation chemistry derived from 1 proceeds through two distinct steps, namely, (1) rate-determining intramolecular alpha-H elimination of neopentane from 1 to form A and (2) 1,2-cis addition of a substrate C-H bond across the W=C linkage in A. The thermolysis of 1 in cyclohexane in the presence of PMe(3) yields 4a-b as well as the olefin complex CpW(NO)(eta(2)-cyclohexene)(PMe(3)) (6). In contrast, methylcyclohexane and ethylcyclohexane afford principally the allyl hydride complexes CpW(NO)(eta(3)-C(7)H(11))(H) (7a-b) and CpW(NO)(eta(3)-C(8)H(13))(H) (8a-b), respectively, under identical experimental conditions. The thermolysis of 1 in toluene affords a surprisingly complex mixture of six products. The two major products are the neopentyl aryl complexes, CpW(NO)(CH(2)CMe(3))(C(6)H(4)-3-Me) (9a) and CpW(NO)(CH(2)CMe(3))(C(6)H(4)-4-Me) (9b), in approximately 47 and 33% yields. Of the other four products, one is the aryl isomer of 9a-b, namely, CpW(NO)(CH(2)CMe(3))(C(6)H(4)-2-Me) (9c) ( approximately 1%). The remaining three products all arise from the incorporation of two molecules of toluene; namely, CpW(NO)(CH(2)C(6)H(5))(C(6)H(4)-3-Me) (11a; approximately 12%), CpW(NO)(CH(2)C(6)H(5))(C(6)H(4)-4-Me) (11b; approximately 6%), and CpW(NO)(CH(2)C(6)H(5))(2) (10; approximately 1%). It has been demonstrated that the formation of complexes 10 and 11a-b involves the transient formation of CpW(NO)(CH(2)CMe(3))(CH(2)C(6)H(5)) (12), the product of toluene activation at the methyl position, which reductively eliminates neopentane to generate the C-H activating benzylidene complex CpW(NO)(=CHC(6)H(5)) (B). Consistently, the thermolysis of independently prepared 12 in benzene and benzene-d(6) affords CpW(NO)(CH(2)C(6)H(5))(C(6)H(5)) (13) and CpW(NO)(CHDC(6)H(5))(C(6)D(5)) (13-d(6)), respectively, in addition to free neopentane. Intermediate B can also be trapped by PMe(3) to obtain the adducts CpW(NO)(=CHC(6)H(5))(PMe(3)) (14a-b) in two rotameric forms. From their reactions with toluene, it can be deduced that both alkylidene intermediates A and B exhibit a preference for activating the stronger aryl sp(2) C-H bonds. The C-H activating ability of B also encompasses aliphatic substrates as well as it reacts with tetramethylsilane and cyclohexanes in a manner similar to that summarized above for A. All new complexes have been characterized by conventional spectroscopic methods, and the solid-state molecular structures of 4a, 6, 7a, 8a, and 14a have been established by X-ray diffraction methods.     

On triazoles. VIII The reaction of 5-amino-1,2,4-triazoles with ethyl 2-cyano-3-ethoxyacrylate and 2-cyano-3-ethoxyacrylonitrile

The reaction of different 5-amino-3-Q-1H-1,2,4-triazoles 1 with ethyl 2-cyano-3-ethoxyacrylate ( 5a ) and 2-cyano-3-ethoxyacrylonitrile ( 5b ) to yield either the a type 5-amino-, or the b type 7-amino-1,2,4-triazolo[1,5-a]-pyrimidine derivatives 6–10 was studied. The structure of compounds 6 and 9 was proved by their degradation to the corresponding derivatives 17a and 18a , respectively, through intermediates 11a, 12a, 13a, 14a, 15a and 16a , respectively. The structure of derivatives 7, 8 and 10 was proved on the basis of the analogy of their uv spectra with those of 6a and 9a , respectively. The isolation of the intermediates 19 and 20 helped to prove the mechanism of the reactions leading to the formation of 6a and 9a , respectively. In the reaction of the N-substituted 5-amino-1,2,4-triazoles with 5a the expected condensed ring products were not formed. Instead the aminoacrylates 22 and 24 were obtained. The “Z”-“E” isomeric structure of derivatives 19, 20, 22 and 24 was proved with the help of their pmr spectra. The “Z” isomeric structure of the thermodynamically stabile 22 was corroborated with the help of its proton coupled cmr spectra, too.     

Synthesis of Enantiomerically Pure Bis(hydroxymethyl)-Branched Cyclohexenyl and Cyclohexyl Purines as Potential Inhibitors of HIV

The synthesis of the enantiomerically pure bis(hydroxymethyl)-branched cyclohexenyl and cyclohexyl purines is described. Racemic trans-4,5-bis(methoxycarbonyl)cyclohexene [(+/-)-6] was reduced with lithium aluminum hydride to give the racemic diol (+/-)-7. Resolution of (+/-)-7 via a transesterification process using lipase from Pseudomonas sp. (SAM-II) gave both diols in enantiomerically pure form. The enantiomerically pure diol (S,S)-7was benzoylated and epoxidized to give the epoxide 9. Treatment of the epoxide 9 with trimethylsilyl trifluoromethanesulfonate and 1,5-diazabicyclo[5.4.0]undec-5-ene followed by dilute hydrochloric acid gave (1R,4S,5R)-4,5-bis[(benzoyloxy)methyl]-1-hydroxycyclohex-2-ene (10). Acetylation of 10 gave (1R,4S,5R)-1-acetoxy-4,5-bis[(benzoyloxy)methyl]cyclohex-2-ene (11). (1R,4S,5R)-1-Acetoxy-4,5-bis[(benzoyloxy)methyl]cyclohex-2-ene (11) was converted to the adenine derivative 12 and guanine derivative 13 via palladium(0)-catalyzed coupling with adenine and 2-amino-6-chloropurine, respectively. Hydrogenation of 12 and 13 gave the correspondning saturated adenine derivative 14 and guanine derivative 15. (1R,4S,5R)-4,5-Bis[(benzoyloxy)methyl]-1-hydroxycyclohex-2-ene (10) was converted to the adenine derivative 16 and guanine derivative 17 via coupling with 6-chloropurine and 2-amino-6-chloropurine, respectively, using a modified Mitsunobu procedure. Hydrogenation of 16 and 17 gave the corresponding saturated adenine derivative 18 and guanine derivative 19. Compounds 12-19 were evaluated for activity against human immunodeficiency virus (HIV), but were found to be inactive. Further biological testings are underway.     

Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13-hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal product

13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)-hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at 37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9-nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b and 4 methyl esters were secured by 15N NMR analysis of the products prepared from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative 3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy intermediates which would partition between two competing routes, viz., loss of HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4 methyl ester and hexanal.     

Selective ther cleavage in the aporphine series. Conversion of (S)-bulbocapnine into (S)-corytuberine and (S)-corydine methyl ether.

Bulbocapnine methyl ether ( 2 ), on treatment with boron halides, affords the aporphine-1,2-diol ( 3 ), the novel aporphines 5 and 6 or the phenanthrene derivative 11 depending on the reaction conditions. 3 can be further transformed into corydine methyl ether ( 4 ); 6 has been converted to corytuberine ( 8 ). Similarly, dehydrobulbocapnine methyl ether 9 was converted to 10 .     

Preparation of 4'-substituted thymidines by substitution of the thymidine 5'-esters

tert-Butyl thymidylate 3 was prepared from thymidine 1 in six steps and 67% overall yield. When the lithium trianion of 3 (prepared by treatment of 3 with excess LDA and then excess tert-butyllithum) is reacted with electrophiles, trapping occurs stereoselectively from either the alpha- or beta-face depending on the electrophile (Scheme 1). Deuterioacetic acid in deuteriomethanol affords mainly the alpha-deuterated product (4a/4b = 2.4:1) while all other electrophiles, e.g., phenylselenenyl chloride, allyl bromide, and N-fluorobenzenesulfonimide (NFSI), give predominately (or completely) the products of attack from the beta-face (5bcd/4bcd = 3.7:1 to 100:0). The structures of the products were determined by coupling constant analysis of both the initial compounds and the diols 6bcd prepared by ester reduction and by formation of the acetonides 7bc. The methyl ester of the 3'-epimer of thymidylic acid 9 was also prepared from thymidine 1 in nine steps and 74% overall yield. When the lithium trianion of 9 (prepared by treatment of 9 with excess LDA and then excess tert-butyllithum) is reacted with electrophiles, trapping also occurs stereoselectively with attack on either the alpha- or beta-face depending on the electrophile (Scheme 2). Again, deuterioacetic acid in deuteriomethanol affords mainly the beta-deuterated product (11a/10a = 1.6:1) while all other electrophiles, e.g., phenylselenenyl chloride, methyl iodide, allyl bromide, and NFSI, gave predominately (or completely) the product of attack from the alpha-face (8.7:1 to 100: 0). Again, the structures of the products were determined by coupling constant analysis of both the initial compounds, and the diols 12b-e were prepared by reduction of the ester and by formation of the acetonides 13bcd. A rationale has been developed using molecular mechanics calculations to explain the diastereoselectivity that involves staggered axial attack on the sp(2) carbon opposite to the pseudoaxial alkoxy group in the most stable half-chair conformation of the enolates, as shown in Schemes 3-5.     

Influence of the heterocyclic side ring on orientation during nitrations of 1,2-alkylenedioxy-annelated benzenes and their mononitro derivatives

Nitration of 1,2-alkylenedioxybenzenes 1 furnished the respective nitro derivatives 3 and 4 in the relative ratios: 4a:3a /100:trace, 4b:3b /98:2.4, 4c:3c /86:14, 4e:3e /91:9 and 4f:3f /99:1.3. Nitration of 4 gave 5a:6a:8a /0:0:100, 5b:6b:8b /7.7:3.2:89, 5c:6c:8c /23:12:65, 5d:6d:8d /14:74:12, 5e:6e:8e /27:18:55 and 5f:6f:8f /23:7.0:70. Nitration of the isomeric 3 afforded the dinitro products 5, 6 and 7 in the following relative ratios: 5a:6a:7a /92:8:0, 5b:6b:7b /80:20:0, 5c:6c:7c /69:20:1 1, 5d:6d:7d /45:19:36, 5e:6e:7e /37:57:5.9 and 5f:6f:7f /64:36:0. Nitration of 3-nitro-1,2-dimethoxybenzene ( 9 ) furnished: 10:11 /63:37. Orientation as a function of the heterocyclic ring-size is discussed.     

Photoaddition of Ethyl 2,2-Dimethyl-5-oxo-5,6-dihydro-2H-pyridine-1-carboxylate to 2,3-dimethylbut-2-ene

On irradiation (350 nm) in the presence of excess 2,3-dimethylbut-2-ene, the newly synthesized title compound 5 affords as main products the unexpected cyclopropylpyrrolidine 10 (50%) and the spiro-oxetane 9 (25%).