Completely stereoselective synthesis of all four stereoisomeric 1-carbamoyloxy-1,3-alkadienes via anti-diastereoselective homoaldol reaction from aldehydes and a single carbon-three-unit

Lithiation of both ($\text{Z}$)- and ($\text{E}$)-3-trimethylsilyl-2-propenyl $\text{N}$,$\text{N}$-diisopropyl carbamate 2 affords the (2$\text{E}$) -lithium compound 3. Aluminium- or titanium-mediated addition to aldehydes, 4 gives (1$\text{E}$)-(3$\text{R}$*4$\text{S}$*)-enol carbamates 7. A stereospecific Peterson elimination (borontriflouride- or base-mediated) introduces the second double bond either with (3$\text{E}$)- or with (3$\text{Z}$)-configuration. So just by reagent selection for each of the two steps, (1$\text{E}$,3$\text{E}$)-, (1$\text{E}$,3$\text{Z}$)-, (1$\text{Z}$,3$\text{E}$)-, or (1$\text{Z}$,3$\text{Z}$)- dienes 8 - 11, respectively, are prepared with stereoselectivities up to > 99.7%     

Nucleosides-126: Selective methylation of the C-nucleoside, ψ-isocytidine and its 2$́-deoxy analog. Synthesis of 1-methyl, 3-methyl and 4-o-methyl derivatives

Methods were developed to prepare 1 -methyl-, 3-methyl- and 4-0-methyl-ψ-isocytidine by selective methylation.3$\text{,}\text{?}$5$\text{-}\text{?}$O-Tetraisopropyldisiloxanyl-ψ isocytidine (8) was trimethylsilylated and then treated with MeI and, after deprotection, 1 -methyl-ψ isocytidine (6) was obtained. The 2$\text{-}\text{?}$deoxy analog (7) was also prepared in a similar manner from the 2$\text{-}\text{?}$deoxy analog (10) of 8. Treatment of 8 with CH₂N₂ afforded the 3-methyl-ψ-isocytidine derivative (19) as the major product. Methylation with diazomethane also occurred mainly on N3 of the 2$\text{-}\text{?}$deoxy analog 10 to form 20. Removal of the 3$\text{,}\text{?}$ 5$\text{-}\text{?}$O-protecting group from 19 and 20 afforded 3-methyl-ψ-isocytidine (14) and its 2-deoxy analog (15), respectively. 2-N-Acetyl- 3$\text{,}\text{?}$5$\text{-}\text{?}$O-tetraisopropyldisiloxanyl-ψ-isocytidine (24), on the other hand, gave the 4-O-methyl derivative (25) as the major product upon CH₂N₂ treatment. Subsequent deprotection of 25 afforded 4-O-methyl-ψ-isocytidine (29). aiv51b1p33b     

Verbrückte und unverbrückte norbornyl-kationen in der gasphase. Berechnungen zur stabilität isomerer norbornyl-kationen mit hilfe quantenmechanischer verfahren

The geometry and the relative stability of bicyclic compounds 1–20 have been calculated by standard quantum mechanics methods.MINDO/3 yields the following stability order of isomeric norbornyl cations (relative energies in $\text{kcal}\text{mole}$): 1-norbornyl cation 9 (0.0); 1.7 σ-bridged cation 6 (0.7); 7-norbornyl cation (nonplanar) 7 (1.1); 2-norbornyl cation (classical) 2 (4.2); 7-norbornyl cation (planar) 8 (4.3); 2-norbornyl cation (bridged) 1 (6.1). The stability of the same ions calculated by ab initio methods (STO-3G, MINDO/3-geometry) leads to an order more nearly consistent with experimental results: 2-norbornyl cation (classical) 2 (0.0); 2-norbornyl cation (bridged) 1 (5.9); 7-norbornyl cation (planar) 8 (11.1); 1-norbornyl cation 9 (14.6); 7-norbornyl cation (nonplanar) 7 (21.2). For the secondary 7-norbornyl cation, MINDO/3 gives a pyramidal configuration, 3.2 $\text{kcal}\text{mole}$ more stable than the planar form. In contrast, the ab initio results (complete optimization of all geometrical parameters) indicate the planar cation to be the most stable form. The bridged structure of 2-norbornyl cation 1 is calculated (STO-3G, partly optimized) to be 4.3 $\text{kcal}\text{mole}$ less stable than the classical counterpart, 2. For the lower homologues 12 and 13 (STO-3G, complete geometry optimization), this difference is 6.4 $\text{kcal}\text{mole}$. However, more extended basis sets should favour the bridged structures. The hydrogen bridged norbornyl cations 3, 4, and 5 have been calculated (STO-3G, partly optimized) to be 14.4, 23.6 and 29.9 $\text{kcal}\text{mole}$ less stable than 2. The stability differences between the corresponding tertiary bicyclic ions 10 vs 11, and 14 vs 15 are calculated (ab initio) to be 15.3 and 19.0 kcal/mole, respectively, in favour of classical structures. The influence of methyl substitution at positions C₁ and C₆ (exo) on bridged and unbridged structure of 2-norbornyl cation is calculated. Pyramidal secondary and tertiary 2-norbornyl cations 19 (a; R=H, b; R=CH₃) and 20 (a; R=H, b; r=CH₃) have been used to model the electrical effects in the solvolysis transition states of epimeric 2-norbornyl esters. Due to more efficient hyperconjugation the pyramidal exo cation is stabilized more than the endo cation by 5.2 $\text{kcal}\text{mole}$ for the secondary series and 3.5 $\text{kcal}\text{mole}$ for the tertiary series. Bonding of endo cation 20 with a nucleophile should be stronger than bonding of exo cation 19 due to more efficient HOMO-LUMO interaction.     

Enamine chemistry—XXIII: The [4+2] cycloaddition reactions between enaminothiones and electrophilic olefins and acetylenes

The enamino-thione, 1c, reacts with acrylonitrile and 2-chloroacrylonitrile at room temperature to give 3,4-dihydro-4-(1-pyrrolidinyl)-2$\text{H}$-thiopyrans, 4 and 5, respectively. The reaction between 1-aryl-3-(1-pyrrolidinyl) (piperidino)-apropene-1-thiones, 1a-c (1d-f), and dimethyl acetylenedicarboxylate gives 4-(1-pyrrolidiny)(piperidino)-4$\text{H}$-thiopyrans, 6a-c (6d-f). Compounds 1a-c (1d-f) and ethyl propiolate produce 2-(1-pyrrolidinyl) (piperidino)-2$\text{H}$-thiopyrans, 8a-c (8d-f), and a new type of rearrangement is observed. The 2$\text{D}$-thiopyran, 9, is formed from 1b and ethyl 3$\text{D}$-propiolate, which elucidates the mechanism. ¹H and ¹³C NMR data of 6 and 7 are discussed.     

Studies on organophosphorus compounds—XXXVI: Simple new routes to phosphorins from 2-hydroxy-, 2-mercapto-, and 2-aminobenzoic acids and their derivatives

2-Hydroxybenzoic acid heated with 2,4 - bis(4 - methoxyphenyl) - 1,3,2,4 - dithiadiphosphetane - 2,4 -disulfide, 1, gave 2 - (p - methoxyphenyl) - 4$\text{H}$ - 1,3,2 - benzoxathiaphosphorin - 4 - one 2 - sulfide, 3, and its thio-analogue, 4, while its ethyl or phenyl esters gave 4 as the sole product. 2 - Mercaptobenzoic acid and its ethyl ester when heated with 1 produced 3$\text{H}$ - 1,2 - benzodithiole - 3 - one, 8, 3$\text{H}$ -1,2 - benzodithiole - 3 - thione, 9, and 2- (p - methoxyphenyl) - 4$\text{H}$ - 1,3,2 - benzodithia - phosphorin - 4 - one 2 - sulfide, 10. The reaction of 2 -aminobenzoic acid with 1 gave 1,2 - dihydro - 2 - (p - methoxyphenyl) - 4$\text{H}$ - 3,1,2 - benzoxaphosphorin - 4 - one 2 - sulfide, 12. Reactions of 1 with methyl 2 - aminobenzoate and 2 - aminobenzamides are described. Mechanistic considerations for the formation of the heterocyclic phosphorus compounds are presented.     

A synthetic approach to (+)-aldosterone and its relatives (2)- a stereoselective synthesis of (+)-trans-4,5-(4-methoxybenzo)- 1β , 7aβ - ( 2α-methoxymethyl- 5 -oxofuro) hydrindane

A stereoselectivity in an intramolecular cycloaddition of the olefinic $\text{o}$-quinodimethanes 13 and 23 generated $\text{in}$$\text{situ}$ from the thermolysis of optically active 4β-[2-(4-methoxybenzocyclobutenyl)ethyl] -5α-methoxymethyl-3-phenyl-thio-methylenefuran-2-ones 12 and 22, respectively, is studied and a stereoselective synthesis of (+)-$\text{trans}$-4,5-( 4-methoxybenzo) -1β,7aβ-(2α-methoxymethyl-5-oxofuro)hydrindane 1 is also described.     

Photocyclization of n-[ω-(cycloalken-1-yl)alkyl]-and n-[ω-(inden-3-yl)alkyl]phthalimides : Synthesis of spiro-nitrogen multicyclic systems

Photolysis of the N-[ω-(cycloalken-1-yl)alkyl]phthalimides 6b-$\text{e}$ in each case gave a pair of stereoisomers of spiro-nitrogen multicyclic systems (9b-$\text{e}$) in moderate yields, whose stereochemistry was determined by means of chemical and spectroscopic analyses. Similarly, in N-[ω-(inden-3-yl)alkyl]-phthalimides (8), spiro-nitrogen macrocycles up to 13-membered 13a-$\text{c}$ were obtained in good yields     

Cyclic acetals as carbonyl blocking groups in the photo-fries rearrangement of acyl substituted aryl esters.

The ethylene acetals of $\text{o}$ and $\text{p}$-acetoxyacetophenone 3a,b, prepared from the corresponding hydroxyacetophenones by treatment with acetic anhydride in pyridine and subsequently with ethylene glycol and $\text{p}$-toluenesulphonic acid, give upon irradiation the expected photo-Fries products 4a,b (from 3a) or 6 (from 3b). These compounds are converted in part into diacetylphenols 5a,b as a consequence of a deacetalization, occurring to some extent during the irradiation and further in the chromatographic workup. The yields of the photoproducts and the $\text{ortho}$/$\text{para}$ ratio (in the case of 3a) are very similar to those given in the literature for phenyl acetate. By contrast, the acetoxyacetophenones 2a,b do not undergo any appreciable change upon irradiation,showing the deactivating effect of the acetyl side chain. Therefore, it is concluded that cyclic acetals are suitable carbonyl blocking groups in order to circumvent the deactivating effect of acyl substituents on the photo-Fries rearrangement of aryl esters.     

Synthesis of novel macrobicyclic polyfunctional cryptands

A pathway yielding both $\text{syn}$ and $\text{anti}$-functionalized macrocycles derived from bis-tartaro-18-crown-6 (1) as well as a selective route to $\text{syn}$ compounds have been developed and applied to the synthesis of new macrobicyclic polyether cryptands (2) and (3), which may also be obtained by direct bridging of the dianhydride (4).     

o-quinone methides 2. Stereoselectivity in cycloaddition reactions of o-quinone methides with vinyl ethers

Cycloaddition reactions between vinyl ethers 3 and $\text{o}$-quinone methides 2, thermally generated from 2-hydroxybenzyl alcohols 1, have been studied. The structure and conformational preferences of the 4-substituted 2-ethoxy-(2,3)-dihydro-2$\text{H}$-benzopyrans 4–9 obtained, which show new interesting features, are discussed together with competitive kinetic data. The cycloaddition process is concerted and involves $\text{o}$-quinone methides in the $\text{E}$-configuration. The OEt-$\text{endo}$ transition state seems to be preferred with ethyl vinyl ether and $\text{Z}$-1-propenyl ethyl ether, whereas with $\text{E}$-1-propenyl ethyl ether the stereoselectivity of the cycloaddition process depends on substituents on the methylene group of the starting alcohol 1. These results are discussed in terms of $\text{endo}$ and $\text{exo}$ preference of the propenyl ether methyl group.     

Biosynthetic pathway of iridoid glucosides in Gardenia jasminoides f. grandiflora cell suspension cultures after iridodial cation formation

Administration of ²H- or ¹³C-labeled monoterpenes to $\text{Gardenia}$$\text{jasminoides}$ f. $\text{grandiflora}$ cell suspension cultures demonstrated that iridoid glucosides of the suspension cultures are biosynthesized, after iridodial cation formation from 10-oxocitral (3), via 8-epiiridodial (13), 8-epiiridotrial (14), boschnaloside (8-epiiridotrial glucoside) (12) and dehydroiridotrial glucoside (8). In addition, the coexistence of a route via iridodial cation (4), dehydroiridodial (6), dehydroiridotrial (15) and dehydroiridotrial glucoside (8) is conceivable.     

Chiral 1,4-benzodiazepines—-XI: Kinetics of degenerate nucleophilic exchange of C(3)-hydroxy group

The rate for degenerate nucleophilic exchange (k_e) of the C(3)-OH group in the racemic compound 1 was determined in DMSO/H₂¹⁸O using mass spectrometry. Epimerization rates for diastereomers 15 and 16 were determined by polarimetry (k_ep) and NMR spectroscopy (k_r-c—for $\text{r}$ing-$\text{c}$hain tautomery). The ratio $\text{k}{}_{\mathrm{e}}\text{k}{}_{\mathrm{ep}}$ ~ 3.5 35° is close to that obtained for degenerate nucleophilic exchange of the C(3)-OMe group in the compound 1a ($\text{k}{}_{\mathrm{e}}\text{k}{}_{\mathrm{\alpha }}$ ~4, Refs. [3,4]). These data confirm the C(3)-OH substituted 1,4-benzodiazepin-2-ones lose the configurational identity of the C(3) chiral centre by both direct nucleophilic substitution of the OH group, and ring-chain tautomery processes.The synthesis of the diastereomeric compounds 15 and 16, and their chromatographic separation is described.     

The unexpected intramolecular C-arylation of 2-0-benzylated cyclic sugar derivatives: a useful 1,2-cis-C-glycosylation reaction

Upon treatment with tin(IV) chloride, perbenzylated glycofuranosyl acetates such as 3 or 6 undergo an unusual, intramolecular α-$\text{C}$-arylation resulting from the internal Friedel-Crafts alkylation of the 2-$\text{O}$-benzyl substituent.     

Transfer to monomer in the polymerization of N-(3-dimethylaminophenyl) maleimide and N-(3-dimethylamino-6-methylphenyl) maleimide

The kinetics of the homopolymerizations of styrene, N-(3-dimethylaminophenyl) maleimide (I) and N-(3-dimethylamino-6-methylphenyl) maleimide (II) in benzene and dimethylformamide, and the molecular weights of the polymers were studied. N-(3-Dimethylaminophenyl) succinimide, regarded as a model for polymer I, did not affect the polymerization of styrene. The data indicate degradative transfer of polymer radicals to dimethylformamide and pronounced transfer to monomers I and II (C_M ≈ 0.06–0.07). The value of $\text{k}{}_{\mathrm{p}}\text{/k}{}_{\mathrm{t}}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ for II is 0.09 $\text{dm}{}^{\mathrm{<mtext>3</mtext><mtext>2</mtext>}}$$\text{mole}{}^{\mathrm{<mtext>?</mtext><mtext>1</mtext><mtext>2</mtext>}}$$\text{s}{}^{\mathrm{<mtext>?</mtext><mtext>1</mtext><mtext>2</mtext>}}$.     

Termination and transfer of the polymer chain to a maleimide derivative containing the azo group

The copolymerizations of N-(3-dimethylaminophenyl) maleimide (I) and 4-(2-chlorophenyl)azo-3-maleimido-N,N-dimethylaniline (II) with styrene were investigated; the copolymerization parameters of the pairs ($\text{I}\text{+}\text{styrene}$) and ($\text{II}\text{+}\text{styrene}$) and $\text{k}{}_{\mathrm{p}}\text{/k}{}_{\mathrm{t}}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ hr I at 50° were determined; chain transfer to the maleimide ring of I was proved. The homopolymerization of styrene in the presence of 4-(2-chlorophenyl)azo-succinimide-N,N-dimethylaniline (III) was used to determine the ratio of the rate constant for addition of the polystyrene radical to the azo group in III to k_p for styrene.     

Conformational effects in compounds with 6-membered rings—XIII : Detection of twist conformers using 13C NMR chemical shifts

¹³C NMR spectra of derivatives of cyclohexane, piperidine, and thian in chair and twist eonformers, and of model compounds, lead to estimates of deshielding (Δδ = 3.6 ± 0.2 ppm) for axial C$\text{Me}$₃ on a cyclohexane ring and shielding (Δδ = ?0.2 to ?0.6 ppm) for ψe-C$\text{Me}$₃ in twist conformers, relative to equatorial C$\text{Me}$₃. Ring carbon atoms are considerably shielded in twist conformers relative to chair eonformers. The value of ¹³C chemical shifts in the study of chair-twist equilibria is exemplified by variable temperature measurements on diastereomeric pairs of compounds (11 and 13; 38 and 50).     

Preparation and reactivity of mesoionic 1,2,4-triazolo-[4,3-b]-1,2,4-triazole derivatives

A number of mesoionic compounds (2) derivatives of the 1,2,4-triazolo[4,3-$\text{b}$]-1,2,4-triazole ring system have been prepared from 4-amino-1 -methyl -3,5-bis(methylthio)- 1,2,4-triazolium cation and aryl isothiocyanates. Compounds ((2) react with methyl iodide to give the methiodides ((3) which undergo ring opening to the monocyclic compounds ((4) through sulfur extrusion under thermal conditions. Methiodides ((3) by sequential treatment with malononitriIe and hydrochloric acid lead to the pyrazolo[5,1-$\text{c}$]-1,2,4-triazole (6).