Reactions of the 1-halo-7-(2-hydroxyethoxy)cycloheptenes and the 3-halo-4-(2-hydroxyethoxy)bicyclo[3.2.1]oct-2-enes with potassium t-butoxide

Reactions of 1 - bromo - 7 - (2 - hydroxyethoxy)cycloheptene 2 and its chloro analogue 3 with potassium t-butoxide in dimethyl sulphoxide or tetrahydrofuran gave cycloheptatriene and cis - 8,11 - dioxabicyclo[5.4.0]undec - 2 - ene 18 as the major products together with small amounts of the trans-isomer 17,8,11-dioxabicyclo[5.4.0]undec - 1(7) - ene 14, 8,11 - dioxabicyclo[5.4.0] - undec - 1 - ene 19, cyclohept - 2 - enone ethylene ketal 15, cyclohept - 3 - enone ethylene ketal 16, and 1- and 2 - t - butoxycyclohepta - 1,3 - diene 20. Similar reactions of 3 - bromo - and 3 - chloro - 4 - (2 - hydroxyethoxy)bicyclo[3.2.1]oct - 2 - ene 4 and 5 gave 4,7 - dioxatricyclo[7.2.1.0^3,8]dodeca - 2 - ene 26 as the major product together with small amounts of 3,6 - dioxatricyclo[7.2.1.0^2,7]dodeca - 2(7) - ene 27 and bicyclo[3.2.1]oct - 3 - ene - 2 - one ethylene ketal 28. Mechanisms for these transformations are discussed.     

Ab initio studies of the allylic hydroxylation: DFT calculation on the reaction of 2-methyl-2-butene with selenium dioxide

The mechanism of the allylic oxidation of 2-methyl-2-butene with selenium dioxide has been investigated by ab initio quantum mechanics. Transition states for two major steps (an ene reaction and a [2,3]-sigmatropic rearrangement) of this reaction have been optimized by the B3LYP/6-311+G(d,p) method. A comparison of the energies of the transition states shows that the anti-endo and syn-endo approaches are the efficient routes in the ene reaction and the methyl (C4) group is sited in a pseudo-equatorial environment in cyclic transition states during the [2,3]-rearrangement. Calculations also show the kind of the terminal alkyl (C4) substituents may control (E)-selectivity in the formation of the allylic alcohols.     

Competitive thermal ene reaction and Diels-Alder reactions of 2-[N-(alk-2-enyl)benzylamino]-3-vinylpyrido[1,2-a]pyrimidin-4(4H)-ones

Thermal reaction of 2-[N-(alk-2-enyl)benzylamino]-3-(2-substituted and 2,2-disubstituted)vinylpyrido[1,2-a]pyrimidin-4(4H)-ones gave azepine, the desired ene products, and/or pyran derivatives. The formation of the latter was responsible for the [4+2] cycloaddition reaction between the α,β-unsaturated ester carbonyl moiety as a diene part and the alkenylamino moiety as an ene one. The reaction features depended upon the kinds of substituents both on the vinyl and alkenyl counterparts; strongly electron-withdrawing substituents on the vinyl moiety or an electron-donating substituent on the alkenyl one changed the reaction feature from the ene reaction to the hetero Diels-Alder reaction.     

Addition reactions of nucleophiles to dibenzoylacetylene

Several enamine diones have been prepared through the nucleophilic addition of different amines to dibenzoylacetylene (DBA). Thus, the reaction of aniline, piperidine, o-aminophenol and N-phenylbenzylamine with DBA gave the corresponding 1:1 adducts namely, 1,4 - diphenyl - 2 - (N - phenylamino)but - 2 - ene -1,4 - dione (1), 1,4 - diphenyl - 2 - piperidinobut - 2 - ene - 1,4 - dione (2), 2 - (N - 2 - hydroxyphenylamino)1,4 - diphenylbut - 2 -ene - 1,4 - dione (3) and 1,4 - diphenyl - 2 - (N - phenylbenzylamino)but - 2 - ene - 1,4 - dione (4). UV absorption data reveal that the adducts 1 and 3, formed from aniline and o-aminophenol, respectively, are the E-isomers, arising through a trans-mode of addition whereas the adducts 2 and 4, formed from piperidine and N-phenyl-benzylamine are the Z-isomers, formed through a cis-mode of addition.The reaction of N-phenaeylaniline with DBA gave 2,3 - dibenzoyl - 1,4 - diphenylpyrrole (5), whereas the reaction of 1,8 - diaminonaphthalene with DBA gave a mixture of products consisting of 2 - benzoyl - 2 - phenacyl -2,3 - dihydroperimidine (11) and 2 - benzoylperimidine (12). The reaction of 2-aminopyridine with DBA gave a mixture of two 1:1-adducts, 2 - (2 - imino - 1(2H) - pyridyl) - 1,4 - diphenylbut - 2 - ene - 1,4 - dione (14) and 1,4 -diphenyl - 2 - (N - 2 - pyridylamino)but - 2 - ene - 1,4 - dione (15).     

Regioselectivity in the ene reaction of singlet oxygen with ortho-prenylphenol derivatives

The ene reaction of singlet oxygen with prenylated dihydroxyacetophenones led to the 2-hydroperoxy-3-methylbut-3-enyl derivatives as the major product. This original regioselectivity outlined a new effect, in competition with the previously established large group non-bonding effect. The oxidation products distribution could be explained by a stabilising interaction between the phenolic hydrogen, ortho to the prenyl side chain, and the perepoxide intermediate.     

Propellanes-XXVIII : Electrophilic reactions of propellanes: epoxidation of olefinic propellanes

Epoxidation of 12 - oxa[4.4.3]propella - 3,8 - diene and 12 - oxa[4.4.3]propell - 3 - ene is less selective than that of 11,13 - dioxo - 12 - methyl - 12 - aza[4.4.3]propella - 3,8 - diene and 11,13 - dioxo - 12 - methyl - 12 - aza[4.4.3]propell - 3 - ene. In the latter two substrates attack syn-to the imide ring is greater than that anti- to it.     

Stereoselective synthesis of the cis-decalin subunit of vinigrol via three pericyclic reactions in cascade

Synthesis of the cis-decalin portion of vinigrol using a tandem oxy-Cope/Claisen/ene reaction is described. This three pericyclic reaction cascade proves to be a valuable synthetic tool in the construction of such systems.     

Studies on pyrrolidinones. Oxidations and rearrangements in the hexahydrobenz[f]indolizine-3,10-dione series

Air oxidation of hexahydrobenz[f]indolizine-3,10-diones in MeOH/MeONa yields alcohols, which are easily and selectively transformed, in very good yields, to succinimides, isoquinoline propanoic acids or dehydrated to ene lactams.     

Novel,efficient and stereospecific synthesis of xylo-(2R,3S,4S)-phytosphingosine and threo-(2R,3R)-sphingosine

The stereo- and regioselective elaboration of a bromohydrin from an olefinic precursor and Pummerer ene reaction for carboncarbon bond formation are the key steps in a novel and flexible synthesis of xylo-phytosphingosine and threo-sphingosine.     

A versatile method for carbon-nitrogen bond formation via ene reactions of acylnitroso compounds

The use of acylnitroso compounds of the general formula RCONO as enophiles in the formation of carbon-nitrogen bonds is described. Both inter- and intramolecular ene reactions have been studied. For the intermolecular examples, nitrosocarbonylmethane, thermally liberated from its Diels-Alder adduct with 9,10-dimethylanthracene, is reacted with various olefins giving the corresponding N-alkylhydroxamic acids in moderate to high yields, providing an efficient method for allylic amidation. The regiochemistry of the intermolecular reaction is observed to be the result of kinetic control, and the direction of addition is consistent with attack by the olefin on electron-deficient nitrogen. Several examples of intramolecular ene cyclization are demonstrated, providing efficient entry into both spiro and fused bicyclic nitrogen containing systems which can be viewed as derived from annulation of 5- and 6- membered nitrogen containing rings onto 5- and 6-membered carbocycles, respectively. Various examples of this hetero-annulation scheme are described. Experimental details are also privided describing typical reaction procedures.     

N-Cbz sulfilimines as valuable intramolecular nucleophiles for the stereoselective synthesis of (−)-deoxocassine and (+)-desoxoprosophylline

N-Cbz sulfilimine, prepared from the corresponding sulfoxide using the Burgess reagent, has been employed as an intramolecular nucleophile for the regio- and stereoselective preparation of a bromo-carbamate from an alkene. The bromo-carbamate has been utilized as an advanced common synthon for the synthesis of deoxocassine and desoxoprosophylline employing the ene and amidomercuration as key reactions.     

Sc(OTf)3-catalyzed one-pot ene-Prins cyclization: a novel synthesis of octahydro-2H-chromen-4-ols

(R)-Citronellal undergoes initial ene reaction followed by Prins cyclization with aldehydes in the presence of 5 mol % of scandium triflate at ambient temperature to furnish octahydro-2H-chromen-4-ols in good yields and with high cis-selectivity. The use of scandium triflate makes this procedure simple, more convenient, and practical.     

Theoretical Studies on the Diastereoselectivity in the Lewis Acid Catalyzed Carbonyl?Ene Reaction: A Fundamental Role of Electrostatic Interaction

Lewis acids affect reactivity, selectivity, and mechanism in the carbonyl‐ene reaction. The diastereoselectivity in the glyoxylate‐ene reaction depends on Lewis acids. While the SnCl₄‐promoted reaction can be achieved with a high level of anti‐selectivity, the use of Al reagents leads to a high syn‐selectivity. The origin of the Lewis acid dependency of the diastereoselectivity in the carbonyl? ene reaction of (E)‐but‐2‐ene with glyoxylate was theoretically studied (HF/6‐31G*) from the point of view of differences and similarities between the ene and the Diels–Alder reactions. Though it has been widely accepted that the endo‐preference would be less obvious in the ene reaction than in the Diels–Alder reaction, our ab initio molecular studies showed that the electrostatic interaction between carbonyl O‐atom lone pair and cationic allylic central C‐atom of ene component exists in the Lewis acid‐promoted carbonyl–ene reaction to affect the transition‐state conformation. It is illustrated that such an electrostatic interaction is essential to control the exo/endo‐selectivity, which provides the diastereoselectivity of the product in the transition state of the Lewis acid promoted carbonyl? ene reaction.     

Dimethylaluminum halide induced reactions of formaldehyde with alkynes. Synthesis of α-allenic alcohols and Z-3-chloroallylic alcohols

The CH₂O·Me₂AlCl complex reacts with terminal alkynes to give α-allenic alcohols via a formal ene reaction and Z-3-chloroallylic alcohols via a stereospecifically syn Friedel-Crafts addition.     

Reaction d'elimination-1,3 : Aciton du n-butyl lithium sur les iodométhyl-2 tosyloxy-1 cyclohexanes (ènes) cis et trans. Stéréochimie et mécanisme

The reaction of cis and rans 2-iodomethyl 1-tosyloxycyclohexanes and 4-enes with nBuLi was studied and found to be stereospecific, the products being respectively bicyclo(4.1.0)hexane (ene) cis and methylene cyclohexane (ène). A parallel is drawn between this reaction and alkaline deshydrohalogenation of cyclic 1,2-halohydrins; a reaction pathway is proposed.     

New route to optically active amine derivatives: ruthenium-catalyzed enantioselective hydrogenation of ene carbamates

The reaction of cyclic ketones with tert-butyl or benzyl carbamate under acidic conditions directly affords prochiral ene carbamates. Their enantioselective hydrogenation in the presence of a chiral ruthenium catalyst provides a new access to optically active carbamates easy to deprotect to the corresponding optically active amines.     

A novel tandem ene/Prins cyclization for the synthesis of octahydropyrano[2,3-c]pyrrole derivatives

A tandem ene/Prins cyclization of olefin tethered aldehyde with an aldehyde has been accomplished using 5 mol % scandium triflate at ambient temperature to afford a novel series of cis-fused octahydropyrano[2,3-c]pyrrole derivatives in good yields with high selectivity. This is the first report on a tandem cyclization of 4-methyl-N-(3-methylbut-2-enyl)-N-(2-oxoethyl)benzenesulfonamide with aldehydes.     

Influence of the alkene structure on the mechanism and kinetics of thiol–alkene photopolymerizations with real‐time infrared spectroscopy

The effect of the chemical structure on the reactivity of alkenes used in thiol–ene photopolymerizations has been investigated with real‐time infrared spectroscopy. Model studies of thiol–ene photoreactions with various monofunctional hydrocarbon alkenes and the monofunctional thiol ethyl‐3‐mercaptopropionate have been performed to identify and understand structure–reactivity relationships. The results demonstrate that terminal enes react very rapidly with thiol, achieve complete conversion, and are independent of the aliphatic hydrocarbon substituent length. Disubstitution on a single carbon of a terminal ene significantly reduces the reactivity, whereas substitution on the carbon α to the terminal ene has a minimal influence on the reactivity. Internal trans enes display reduced reactivity and a lower overall conversion and deviate from the standard thiol–ene reaction mechanism because of steric strain induced by 1,3‐interactions. The reactivity and conversion of internal trans enes decrease as the substituents on the ene become larger, reaching a minimum when the substituent size is greater than or equal to that of propyl groups. Internal cis enes react rapidly with thiol; however, they undergo a fast isomerization–elimination reaction sequence generating the trans ene, which proceeds to react at a reduced rate with thiol. The reactivity of cyclic enes is dictated by ring strain, stereoelectronic effects, and hydrogen abstractability. The reactivity trends in the model studies have been used to explain the photopolymerization mechanism and kinetics of a series of multifunctional thiol–ene systems. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6283–6298, 2004     

Synthesis of chiral carbosilane dendrimers with l-cysteine and N-acetyl-l-cysteine on their surface and their application as chiral selectors for enantiomer separation by capillary electrophoresis

The synthesis of chiral carbosilane dendrimers functionalized with cysteine and N-acetylcysteine groups is presented. These dendrimers were obtained through thiol–ene addition reactions and their application as chiral selectors in capillary electrophoresis was investigated. Four drugs used as model compounds were analyzed under different experimental conditions observing that the use of a first generation dendrimer containing 4 terminal N-acetyl-l-cysteine groups enabled the enantiomeric discrimination of razoxane with a discrimination power similar to that obtained with other powerful chiral selectors such as cyclodextrins.     

Enantiospecific total synthesis of aciphyllene

Enantiospecific total synthesis of the sesquiterpene aciphyllene and its three epimers have been described starting from the readily available monoterpene (R)-limonene employing an intramolecular type II carbonyl ene reaction as the key step.