Isomerization of unsaturated radicals. V. Unimolecular isomerization of hot α,α- and α,β-dimethallyl radicals

The 147 nm photolysis of 3,3 dimethylbut-1-ene leads mainly to the formation of very hot (?375 kJ/mol) α,α-dimethallyl radicals. On the other hand, that of 3-methyl-cis-and trans-pentene-2, as well as that of 2,3-dimethylbut-1-ene is a source of very hot α,β-dimethallyl radicals. These allylic radicals are coolled down using pressure and are allowed to combine with available methyl radicals. From the formation of various C₆H₁₂ products, it is concluded that the very hot α,α- radical isomerizes towards the α,β-structure at low pressures and vice versa. The equilibrium constant of the following process has been evaluated to be 1.72 ± 0.30.      

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Kinetics of the reactions of cyclopropane derivatives. V. The gas-phase unimolecular reactions of 1 α-chloro-2α,3α-dimethylcyclopropane and 1α-chloro-2α,3β-dimethylcyclopropane

Thermolysis of the “all-cis” compound 1α-chloro-2α,3α-dimethylcyclopropane (A) at 550–607 K and 6–115 torr is a first-order homogeneous non-radical-chain process giving penta-1,3-diene (PD) and HCl as products. The Arrhenius parameters are log₁₀A(sec^?1) = 13.92 ± 0.08 and E = 199.6 ± 0.9 kJ/mol. The isomer with trans-methyl groups, 1α-chloro-2α,3β-dimethylcyclopropane (B) reacts by two parallel first-order processes giving as observed products trans-4-chloropent-2-ene (4CP) and PD + HCl, with log₁₀A(sec^?1) = 14.6 and 13.8, respectively, and E = 199.5 and 190.2 kJ/mol, respectively. The 4CP undergoes secondary decomposition to PD + HCl (as investigated previously). Comparison of the results for compounds (A) and (B) with those for other gas-phase and solution reactions leads to the conclusion that the gas-phase thermolyses proceed by rate-determining ring opening to form olefins which may decompose further by thermal or chemically activated reactions, and that the ring opening is a semiionic electrocyclic reaction in which alkyl groups in the 2,3-positions trans to the migrating chlorine semianion move apart, with appropriate consequences for the rate of reaction and the stereochemistry of the products.     

Über die Stereospezifität der α-Alkylierung von β-Hydroxycarbonsäureestern. Vorläufige Mitteilung

About the Stereospecific α-Alkylation of β-Hydroxyesters It was found, that dianions derived from β-hydroxyesters with lithium diisopropylamide (LDA) at ?50 to ?20° were alkylated stereospecifically (Scheme 1). The stereospecificity was 95–98%, the threo-compound (threo -2, -3 and -4) being the main product. This was proved for threo -2 and -3 by preparing the β-lactones 7 and 8 , respectively, which were pyrolyzed to trans-1, 4-hexadiene (9) and trans-1-phenyl-2-butene (10) , respectively (Scheme 2). Moreover, the acid threo -6 from threo -3 was converted by dimethylformamide-dimethylacetal to cis-1-phenyl-2-butene (11) (s. footnote 6). The alkylation of α-monosubstituted β-hydroxyesters also turned out to be stereospecific. Reduction of 16 and 18 with actively fermenting yeast furnished (+) -17 and (+) -2. respectively (Scheme 4), which were each mixtures of the (2R, 3S)- and the (2S, 3S)-isomers. Alkylation of (+) -17 with allyl bromide yielded after chromatography (2S, 3S) -19 and of (+) -2 with methyl iodide (2R, 3S) -19 , the oxidation of which finally gave (S)-(?) -20 and (R)-(+) -20 , respectively.     

Sythese von α und β-Sinensal

β-Sinensal (2,6-dimethyl-10-methylene-dodeca-2,6,11-trienal) was synthesized from the diene-aldehyde 5 . This was converted into the trans- and cis-triene-aldehydes 16 and 17 , which were condensed with the phosphorane 18 to give the corresponding two geometrical isomers ( 3 and 19 ) of β-sinensal.     

Etude Stéréochimique par RMN 1H de Tetrahydropyrannes β-Chlorés α-Substitués

The ¹H NMR study of 2-alkyl-3-chlorotetrahydropyrans, obtained by reaction of Grignard reagents with a mixture of cis/trans-2,3-dichlorotetrahydropyrans, shows cis/trans configuration of two isomers in which the alkyl substituents are exclusively in the equatorial position. 3-Chloro-2-phenyltetrahydropyran exists in trans (eq-eq) configuration only. The ¹H NMR study of cis/trans 2-alkoxy (or aryloxy)-3-chlorotetrahydropyrans, obtained by reaction of alcohols or phenol with 2,3-dichlorotetrahydropyrans, shows the axial position of the alkoxy (or aryloxy) substituent.     

Reversible,thermische Isomerisierung zwischen α, β-γ, δ-ungesättigten Aldehyden und Alkenylketenen durch [1,5]-H-Verschiebung. Valenzisomerisierung von cis-Dienonen,V [1]

Vapor phase pyrolysis of 2,4-pentadienaldehyde, of 6-oxabicyclo[3.1.0]hex-2-ene or of 3-pentenoic acid chloride at 600° (0.1 s/1 Torr) leads to similar mixtures containing the stereoisomers of 2, 4-pentadienaldehyde and 1-propenylketene. These compounds, and methyl substituted derivatives thereof, equilibrate at 600° (0.1 s) through intramolecular processes involving cis/trans-isomerisations and [1,5]-H-shifts. It is shown that α, β-γ, δ-unsaturated aldehydes can be prepared in high yield through gas phase thermolysis of appropriately substituted acid chlorides.     

Trennung und Charakterisierung von β-Carotin-Isomeren

Separation and Characterization of the cis-Isomers of β,β-Carotene A stable HPLC. system is described allowing the excellent separation of 11 different cis-isomers of β,β-carotene from the all-trans compound. The system is applied to the analysis of cis/trans mixtures obtained from plant extracts and by photoisomerization of the all-trans isomer. Al₂O₃ is used as the stationary phase while hexane with controlled H₂O content is utilized as the mobile phase. With the aid of the optimum conditions 8 sufficiently stable cis isomers were isolated and their structures shown to be the 9-, 13- and 15-cis, the 9,9′-, 9, 13-, 9, 13′- and 13,13′-di-cis and, tentatively, the 9,13,13′-tri-cis β,β-carotenes by application of 270-MHz-FT.-¹H-NMR. spectroscopy.     

Ring-opening polymerization of α,β-disubstituted oxiranes by α-methoxyphenylmethylium hexachloroantimonate

α-Methoxyphenylmethylium hexachloroantimonate was used as a novel initiator for the polymerization of α,β-disubstituted oxiranes such as cyclohexene oxide (CHO) and 2-butene oxide (trans and cis) (2-BO) at ?78°C with dichloromethane or dichloromethane-toluene mixtures as solvents. The CHO polymerization mixture became turbid and the polymer precipitated in dichloromethane. The CHO polymerization proceed quantitatively in dichloromethane–toluene mixtures. The molecular weight distribution of polyCHO obtained was bimodal regardless of the solvent used. The polymerization of trans-2-BO was heterogeneous in both dichloromethane and dichloromethane–toluene mixture. The polymerization mixtures of cis-2-BO were transparent but reached a limit yield which was less than the polymer yield of trans-2-BO. Furthermore, the microstructure of the poly2-BOs were analyzed by Vandenberg's method and the results confirmed Vandenberg's finding that inversion of configuration occurs in the propagation step.     

Reaktionen von α-Chlorcarbonsäurechloriden mit Trialkylaminen

The condensation of α,α-dichloropropionyl chloride (IVa) and of trichloroacetyl chloride (IVb) with α-chloropropionyl chloride (Ia) in the presence of triethylamine led to two acid chloride enol-esters, both as mixtures of cis- and trans-isomers, namely 1, 2-dichloropropenyl α,α-dichloropropionate (Va) and 1, 2-dichloropropenyl trichloroacetate (Vb). A mixture of triethylamine and trichloroacetyl chloride produced an oxidation-reduction reaction to give 48% 1, 2, 2, 2-tetrachloroethyltrichloroacetate (VIII) and 69% 1-diethylamino-4, 4, 4-trichloro-1-butene-3-one (IX). Basic hydrolysis of IX led to 43% of glutaconic acid (XIII). Tripropylamine reacted in the same way with trichloroacetyl chloride to yield 1-dipropylamino-2-methyl-4, 4, 4-trichloro-but-1-ene-3-one (XIX) which was readily hydrolyzed in acid solution to α-trichloroacetyl-propionaldehyde (XX).     

Regio-, Diastereo-, and Enantioselective Synthesis of Vicinal Diols via α-Silyl Ketones

A new versatile and efficient regio-, diastereo-, and enantioselective synthesis of vicinal diols s-trans- 4 , s-trans- 5 , and s-cis- 4 is described. Symmetrical ketones are converted into their SAMP-or RAMP-hydrazones which are then silylated with (isopropyloxy)dimethylsilyl chloride, followed by ozonolysis to afford the α-silyl ketones (R)- 2 of high enantiomeric purity (ee 90– ≥ 98%). On the other hand, methyl ketones, after conversion into the corresponding (?)–(S)-1-amino-2-(methoxymethyl) pyrrolidine (SAMP) hydrazones, are silylated and then alkylated with RI to afford unsymmetrical α-silyl ketones (S)- 3 of high enantiomeric purity (ee 90- ≥ 98%). The reduction of the above obtained α-silyl ketones with L -Selectride, followed by oxidative cleavage of the C? Si bond gives rise to s-trans-4, s-trans- 5 , and s-cis- 4 with high diastereoselectivity (de 95- ≥ 98%) and without racemization (ee ≥ 90– ≥ 98%).     

cis-trans-and Intramolecular enol-enolic equilibrium of β-ketoaldehydes

Tautomerism of aromatic β-ketoaldehydes p-XPhCOCH₂CHO ( 1 , X = NMe₂, OMe, Me, H, Br, NO₂), aliphatic β-ketoaldehydes and benzoylacetaldehyde RCOCH₂CHO ( 2 , R = Me, i-Bu, t-Bu, Ph), RCOCH(Me)CHO ( 3 , R = Me, Et, i-Pr) and methyl 2-formylpropionate MeOCOCH(Me)CHO ( 4 ) has been studied by the ¹H NMR technique. In basic solvents both cis- and trans-enol forms of these compounds co-exist. trans-Enolisation, which occurs exclusively at the formyl group, is most favoured in compound ( 4 ) and least favoured in compounds ( 1 ) and ( 2 ). The increasing electron-attracting property of the substituent X in the aromatic β-ketoaldehydes ( 1 ), as well as increasing solvent basicity in the series propanediol-1, 2-carbonate, acetone < dimethylformamide < dimethylacetamide < pyridine, also shifts the equilibrium towards the trans-enol form. The trans-enol form is absent in aprotic solvents of low basicity such as CCl₄, C₂HCl₃ and toluene. The thermodynamic parameters of the cis-trans-enol (C ? T) and cis-enol-enolic (C ? C') equilibria have been estimated from the temperature dependences. The transition from the cis-to the trans-enol form is accompanied by an entropy decrease of about 10 cal mol^?1 degree^?1. Nevertheless the trans-enol form is stabilised due to its lower enthalpy. The cis-trans-enol equilibrium is determined by the relative strength of the intramolecular hydrogen bond in the cis-enol form and the intermolecular hydrogen bonds with basic solvent molecules of the trans-enol form. The enthalpy difference of the two cis-enolic forms does not exceed 1.0 kcal/mol, in rough agreement with the data calculated by the CNDO/2 approximation. Polar solvents favour the hydroxymethyleneketone form (C) for both groups of compounds 2 and 3 . The content of the hydroxymethyleneketone form is about the same within series 2 where R = Me, i-Bu, Ph and is a little higher for the t-Bu derivative. A decrease of temperature only slightly shifts the equilibrium of compounds 1 and 2 to the hydroxymethyleneketone form, while in the case of 2-methyl-β-ketoaldehydes (3) this effect is markedly pronounced.     

Quinoline syntheses by reaction of hydrazoic acid with α,β-disubstituted cis-chalcones

Hydrazoic-sulfuric acid mixture converted cis-α-phenyl-β-benzoylchalcone (trans-dibenzoylstilbene, 4 ) into 2,3-diphenyl-4-benzoylquinoline ( 5 ) the structure of which was proved by debenzoylation to 2,3-diphenylquinoline. α,β-Diphenyl and cis-α,β-dibromochalcones similarly were converted respectively into 2,3,4-triphenylquinoline ( 19 ) and 2-phenyl-3,4-dibromoquinoline ( 20 ). The structure of 19 was shown by difference from the corresponding isoquinoline 21 (synthesized). Smith's mechanism for the analogous conversion of o-phenylbenzophenone into 9-phenylphenanthridine through the 9-fluorenol and the 9-hydroazide with loss of nitrogen and ring expansion, was supported by methyl label experiments using 2-(p-tolyl)benzophenone which gave a 53:47 mixture of 3- and 8-methyl-6-phenylphenanthridines. Applicability of the mechanism to the reactions with disubstituted cis-chalcones was shown by sulfuric acid conversions of two of these into indenol 22 and 2-bromo-3-phenylindenone ( 24 ), respectively. trans-Dibenzoylstilbene underwent resinification in sulfuric acid, giving the quinoline ( 5 ) only when hydrazoic acid was present.     

α-Alkylierung von β-Hydroxycarbonsäuren über 1,3-Dioxan-4-on-Enolate

Highly Diastereoselective α-Alkylation of β-Hydroxycarboxylic Acids Through Lithium Enolates of 1,3-Dioxan-4-ones From serine, β-hydroxyisobutyric acid (‘Roche’ acid) and β-hydroxybutyric acid, the dioxanones 1–6 were prepared. The generation of the enolates of type I with LDA at ?75° and alkylation gave products with trans-configuration whereas protonation of the 5-methyl-substituted enolate allowed access to the cis-configurated β-hydroxybutyric-acid derivative 12 . Hydrolysis gave the free β-hydroxy acids of ‘syn’-and ‘anti’-configuration. Alkylation of the 6-unsubstituted dioxanones 1 and 3 yielded predominantly products resulting from attack in the cis-position of the t-Bu group. The ‘reactive’ conformation of the enolates involved is tentatively derived from the product configuration. The selectivity of the alkylation is also discussed in terms of the results of an ab-initio calculation on the enolates M–P.     

Die absolute Konfiguration der 3,5-Diaminohexansäure aus der β-Lysin-Mutase-Reaktion

Absolute configuration of the 3,5-diaminohexanoic acid produced in the β-lysine mutase reaction The (3S, 5S)-configuration of the 3,5-diaminohexanoic acid 3 produced by the coenzyme-B₁₂-dependent β-lysine mutase from Clostridium sticklandii has been determined by two different methods: by comparison of the ¹H-NMR.-spectrum of its δ-lactam with that of synthetic (±)-cis-and (±)-trans-4-amino-6-methyl-piperidones ( 1 and 2 ) and by chemical correlation with (+)-(6S)-6-methyl-piperidone-2 ( 9 ).     

Solvolysis and Isomerization of cis- and trans-1-Bromo-1-(p-anisyl)-propene (α-Bromoanethole) Mesomeric Vinyl Cations,Part V

The influence of a β-methyl group on the reactivity of two stereoisomeric vinyl bromides has been studied. In 80% ethanol cis-( 8 ) and trans-α-bromoanethole ( 9 ) undergo first order reactions leading to p-methoxypropiophenone ( 15 ), 1-ethoxy-1-(p-anisyl)-propene ( 16 ) and p-anisylpropyne ( 12 ). Solvolysis of the cis isomer 8 is accompanied by isomerization to the more stable trans isomer 9 which is approx. eight times less reactive than 8 . Cis-trans isomerization is also observed in nitrobenzene at 150°. These results are in agreement with the unimolecular substitution-elimination (S_N1?E1) mechanism which competes with cis-trans isomerization at the ion pair stage. The solvolysis rate of 9 is slightly lower and that of 8 somewhat higher than the rate of α-bromo-p-methoxystyrene ( 3c ). In the absence of other effects a β-methyl group therefore slightly depresses the ionization rate, presumably by steric hindrance of solvation. These results confirm the negligible polar influence of a β-methyl substituent on the stability of vinyl cations.     

Structure and reactivity of α,β-unsaturated ethers. VIII. Cationic copolymerizations and acetal additions of propenyl and isobutenyl ethyl ethers

Cationic copolymerizations of cis- and trans-propenyl ethyl ethers (PEE) with isobutenyl ethyl ether (IBEE) were carried out in methylene chloride at ?78°C with the use of boron trifluoride etherate as catalyst. Monomer reactivity ratios were r₁ = 24.0 ± 2.4 and r₂ = 0.02 ± 0.02 for the cis-PEE (M₁)–IBEE (M₂) system and r₁ = 19.1 ± 1.8 and r₂ = 0.04 ± 0.02 for the trans-PEE (M₁)–IBEE (M₂) system, indicative of the reactivity order: cis-PEE > trans-PEE ? IBEE. In separate experiments, these β-methyl-substituted vinyl ethers were allowed to react with various acetals in the presence of boron trifluoride etherate. The relative reactivities of these ethers were generally found to decrease in the order: cis-β-monomethylvinyl > vinyl > trans-β-monomethylvinyl > β,β-dimethylvinyl. Comparisons of these results with previously published copolymerization data have permitted the conclusion that, in both the copolymerizations and acetal additions, the single β-methyl substitution on vinyl ethers exerts little steric effect against their additions toward any alkoxycarbonium ion, whereas the β,β-dimethyl substitution results in a large adverse steric effect toward both β-monomethyl- and β,β-dimethyl-substituted alkoxycarbonium ions.     

A Flexible Stereoselective Synthesis of the Spirosesquiterpenes (±)-β-Acorenol, (±)-β-Acoradiene, (±)-Acorenone-B and (±)-Acorenone via an Intramolecular Ene-Reaction

The racemic spirosesquiterpenes β-acorenol ( 1 ), β-acoradiene ( 2 ), acorenone-B ( 3 ) and acorenone ( 4 ) (Scheme 2) have been synthesized in a simple, flexible and highly stereoselective manner from the ester 5 . The key step (Schemes 3 and 4), an intramolecular thermal ene reaction of the 1,6-diene 6 , proceeded with 100% endo-selectivity to give the separable and interconvertible epimers 7a and 7b . Transformation of the ‘trans’-ester 7a to (±)- 1 and (±)- 2 via the enone 9 (Scheme 5) involved either a thermal retro-ene reaction 10 → 12 or, alternatively, an acid-catalysed elimination 11 → 13 + 14 followed by conversion to the 2-propanols 16 and 17 and their reduction with sodium in ammonia into 1 which was then dehydrated to 2 . The conversion of the ‘cis’-ester 7b to either 3 (Scheme 6) or 4 (Scheme 7) was accomplished by transforming firstly the carbethoxy group to an isopropyl group via 7b → 18 → 19 → 20 , oxidation of 20 to 21 , then alkylative 1,2-enone transposition 21 → 22 → 23 → 3 . By regioselective hydroboration and oxidation, the same precursor 20 gave a single ketone 25 which was subjected to the regioselective sulfenylation-alkylation-desulfenylation sequence 25 → 26 → 27 → 4 .     

Chemoenzymatic and yeast-catalysed synthesis of diastereomeric ethyl γ-phenyl and γ-(n-pyridyl)paraconates

The synthesis of γ-phenyl and γ-(n-pyridyl)paraconates was accomplished by chemical reduction of their respective ketodiester precursors followed by cyclisation of the resulting hydroxy diester intermediates. The cis- and trans-lactones thus obtained were separated and separately subjected to enzymatic hydrolysis with HLAP. The cis-lactonic esters had enantiomeric excesses ranging from 94% to 99%, while for the trans-isomers the ee’s ranged from 80% to 93%. The same ketodiester precursors were subjected to reduction with a series of yeasts. The absolute configuration of trans-(−)-2-pyridyl paraconic acid was assigned by means of X-ray analysis of its hydrobromide salt, while the absolute configurations of the other lactones were determined via analysis of their respective CD curves.     

Structure and reactivity α,β-unsaturated ethers. II. Cationic copolymerizations of propenyl isobutyl ether

cis- and trans-Propenyl isobutyl ethers were copolymerized with each other and each with vinyl isobutyl ether separately under various conditions. In homogeneous polymerizations a cis-β-methyl substitution on vinyl isobutyl ether apparently enhanced the reactivity, whereas the trans substitution tended to reduce it slightly. In heterogeneous catalysis, on the other hand, a β-methyl group on the vinyl ether, whether cis or trans, greatly reduced the reactivity, probably because of the steric hindrance toward the adsorption of monomers on the catalyst surface. The relative reactivities of cis- and trans-propenyl isobutyl ethers ranged from 2 to 20, depending on the polymerization conditions. The polymer end formed from the cis monomer exhibited special steric effects. It was concluded that even in homogeneous media the rotation of the polymer end around the terminal carbon–carbon bond is restricted.