Lewis acid-mediated radical cyclization: stereocontrol in cascade radical addition-cyclization-trapping reactions

An efficient approach for achieving radical cyclizations by using hydroxamate ester as a coordination tether with Lewis acid was studied. The chiral Lewis acid-mediated cascade radical addition-cyclization-trapping reaction proceeded smoothly with good enantio- and diastereoselectivities, providing various chiral γ-lactams.     

Lewis acid-mediated reactions of donor-acceptor cyclopropanes with diazo esters

The reactions of diazo esters with 2-arylcyclopropane-1,1-dicarboxylates, the represen- tatives of donor-acceptor cyclopropanes (DACs), mediated by Sc(OTf)₃, SnCl₄, and GaCl₃ proceeded with nitrogen elimination to give the C—C coupling products. No products of the formal [3+3] cycloaddition of diazo compounds to DACs were formed but the main reaction direction was addition of diazo ester to either 1,3- or 1,2-zwitterions generated upon Lewis acid-mediated cyclopropane ring opening giving rise to new 1,4- and 1,3-zwitterionic inter- mediates. The formed intermediates underwent further fragmentations and rearrangements to give substituted cyclopropanedi-, -tri-, and -tetracarboxylates. Mechanistic aspects of the observed reactions were discussed.     

Lewis acid-mediated reactions of alkyl azides with alpha,beta-unsaturated ketones

[reaction: see text] Alkyl azides react with saturated ketones upon treatment with Lewis acids to afford ring-expansion products through the azido-Schmidt reaction, but this reaction does not proceed when alpha,beta-unsaturated ketones are used. In this study, alkyl azides were reacted with enones in the presence of Lewis acids to give enaminones (vinylogous amides), which formally involve a ring contraction reaction. The mechanism and scope of this reaction is discussed.     

Chiral ruthenium Lewis acid catalyzed intramolecular Diels-Alder reactions

Single point binding ruthenium Lewis acid catalysts [Ru(acetone)(S,S)-BIPHOP-F)Cp][SbF(6)] ((S,S)-1b) and [Ru(acetone)(S,S)-BIPHOP-F)(indenyl)][SbF(6)] ((S,S)-1c) efficiently catalyze intramolecular Diels-Alder (IMDA) reactions under mild conditions to afford the endo cycloaddition products as the major product in excellent yields with high diastereo- and enantioselectivities.     

Lewis acid promoted phenylseleno group transfer tandem radical cyclization reactions

[reaction: see text] A new Lewis acid promoted phenylseleno group transfer tandem radical cyclization method was developed. In the presence of Lewis acids such as Yb(OTf)3 or Mg(ClO4)2, under photolysis condition at low temperature (-45 degrees C), various unsaturated alpha-phenylseleno beta-keto amides underwent radical cyclization reactions to give monocyclic or bicyclic products in a highly efficient, regioselective, and stereoselective manner.     

Mass spectrometric intramolecular cyclization reactions of some 2-N-phenyliminoperhydro-1,3-oxazines

Mass spectrometric fragmentation of four monocyclic and eight condensed skeleton 2-N-phenyliminoper-hydro-1,3-oxazine derivatives have been characterized by metastable ion analysis, collision induced dissociation measurements, exact mass measurements and ion structural studies. Extensive rearrangement reactions, best characterized in terms of intramolecular cyclizations, took place. Namely, when R = H the N-cyclization was almost exclusive whereas in cases where R > H steric reasons rendered the O-cyclization more feasible. Part of the fragmentation of the R = H compounds seemed to occur via the amino form. On the other hand the methane chemical ionization spectra of cis- and trans-anellated 5,6-trimethylene-2-N-phenyliminoperhydro-1,3-oxazines proved that at least some imino structure was present in the gas phase.     

Studies on tandem ene/intramolecular diels-alder reactions

Tandem ene/intramolecular Diels-Alder reactions of 1,4-cyclohexadiene and - or -activated acetylenes are optimized. Analogous reactions with disubstituted bicyclohexa-1,4-dienes regioselectively produce highly functionalized tetracyclic adducts.     

Readily available (S)-proline-derived organocatalysts for the Lewis acid-mediated Lewis base-catalyzed stereoselective aldol reactions of activated thioesters

A set of enantiomerically pure Lewis bases containing different diphenyl phosphinyl oxide groups were easily synthesized in a straightforward procedure by reaction of readily available proline-based scaffolds and phosphinoyl chlorides. The newly synthesized derivatives were employed (0.1 mol equiv) as organocatalysts in the Lewis acid-mediated Lewis base-promoted direct stereoselective aldol reactions of activated thioesters with aromatic aldehydes, carried out in the presence of tetrachlorosilane and a tertiary amine. β-Hydroxy thioesters were obtained in moderate to high yields, with very high syn diastereoselectivities (dr up to >98:2), and fair enantioselectivities (ee up to 51%). Theoretical studies were performed in order to elucidate the origin of the stereoselection.     

Titanium- and Lewis acid-mediated cyclopropanation of imides

We report a straightforward synthesis of 1-azaspirocyclopropane lactams from imides. Following the described procedure, polycyclic nitrogen heterocycles containing a cyclopropane unit could be obtained from unsaturated imides. [reaction: see text].     

Chiral Lewis acid-catalyzed enantioselective intramolecular carbonyl ene reactions of unsaturated alpha-keto esters

[reaction: see text] Chiral Lewis acid-promoted highly enantioselective intramolecular carbonyl ene reactions of unsaturated alpha-keto esters have been investigated. In the presence of chiral Lewis acids such as [Sc((R,R)-Ph-pybox)](OTf)(3) and [Cu((S,S)-Ph-box)](OTf)(2), several unsaturated alpha-keto esters underwent carbonyl ene reactions in CH(2)Cl(2) at room temperature to give monocyclic products in good yield and excellent enantioselectivity.     

Lewis acid-mediated selective chlorinations of silyl enolate

A new method involving efficient, widely applicable, and highly selective alpha-chlorination of simple silyl enolate with Lewis acid and an alpha,alpha-dichloro-1,3-dicarbonyl controller unit was reported. Diastereoselectivity and enantioselectivity of the reaction were investigated. High reactivity and selectivity were achieved by using alpha,alpha-dichlorinated malonic ester.     

Studies of intramolecular Diels-Alder reactions of nitroalkenes for the stereocontrolled synthesis of trans-decalin ring systems

Studies of thermal IMDA cyclizations of (1E,7E)-1-nitro-deca-1,7,9-trienes and (1E,3Z,7E)-1-nitro-deca-1,3,7,9-tetraenes have been examined. Reactions of these nitroalkenes proceed via transition states featuring characteristics of asymmetric stretch asynchronicity and result in stereoselective formation of trans-fused decalin products. Substantial rate acceleration is observed for IMDA cyclizations exemplified by triene 14 due to steric repulsions of substituents in the tethering chain which promote facile stereocontrolled formation of trans-fused 26.     

Development of efficient Lewis acid catalysts for intramolecular cycloaddition reactions of ester-tethered substrates

We have developed novel bidentate Lewis acids that efficiently promote the intramolecular cycloaddition reactions of ester-tethered substrates. Bis-aluminated triflic amide derivatives [TfN(AlR(1)R(2))2], which are generated by simply mixing triflic amide and 2 equiv of methyl aluminum or aluminum hydride, catalyzed intramolecular Diels-Alder (DA) reactions of ester-tethered 1,7,9-trienes and intermolecular DA reactions of alpha,beta-unsaturated lactones. We also found that bimetallic Lewis acid derived from 1,1'-biphenyl-2,2'-di(triflyl)amide and dimethylaluminum chloride promoted the intramolecular [3 + 2] cycloaddition reaction of acrylate derivatives having an allylsilane part.     

Lewis acid-induced intramolecular Friedel-Crafts cyclization of 1,3-bis-exocyclic dienes. a new route to 4a-methyltetrahydrofluorenes

[reaction: see text] An efficient new method for constructing the 4a-methyltetrahydrofluorene skeleton was achieved via Friedel-Crafts intramolecular cyclization of 1,3-bis-exocyclic dienes. This strategy offers a simple and promising method for accessing complex structures.     

Quantitating the effect of an ortho substituent on cyclization and intramolecular hydrogen-transfer reactions of aryl radicals

Reduction of allyl 2-iodobenzyl malonates with triphenyltin hydrides generates aryl radicals that partition between 6-exo cyclization, 7-endo cyclization, and 1,5-hydrogen atom transfer. Rate constants for all of these processes are high (>10(8) M(-)(1) s(-)(1)), and the rates are only marginally reduced (<33%) by the introduction of methyl group ortho to the reacting radical.     

A DFT study of the ambiphilic nature of arylpalladium species in intramolecular cyclization reactions

The remarkable structure-dependent reactivity observed in the cyclization of (2-haloanilino)-ketones with Pd-catalysts has been studied computationally within the density functional theory framework. The experimental reaction products ratio may be explained through the formation of a common palladaaminocyclobutane intermediate which can undergo a nucleophilic addition reaction and/or an enolate α-arilation process. The evolution of this metallacycle to the final products depends on two factors, the length of the tether joining the amino and the carbonyl groups, and the electronic nature of the substituent directly attached to the nitrogen atom. Thus, shorter chains (2 CH(2)) facilitate the nucleophic addition reaction by approximating the reactive aryl and Pd-coordinated carbonyl groups whereas longer chains (3 CH(2)) favor the enolate α-arylation proccess. For electron-withdrawing groups attached to the aniline nitrogen atom, the nucleophilic addition pathway becomes slightly disfavored, mainly due to the electron-withdrawing effect of the CO(2)Me group which avoids the delocation of the LP in the π-system, thus decreasing the nucleophilicity of the reactive arylic carbon atom. In contrast, the enolate α-arylation reaction is facilitated by the CO(2)Me group. This is translated into a small computed barrier energy difference of these competitive reaction pathways which should lead to a mixture of reaction products as experimentally found.     

Synthesis of macrocyclic terpenoids by intramolecular cyclization V. transannular reactions of hedycaryol isomers

Thermal rearrangement and acid-catalyzed cyclization of all possible geometrical isomers of hedycaryol were investigated. From the stereochemistry of the products, the reacting conformations were deduced. While three (E,E-, E,Z- AND Z,E-) isomers reacted through the crossed conformations, Z,Z-isomer yielded products $\text{via}$ parallel conformations. The thermal reaction at higher temperatures revealed the additional pathways involving Cope rearrangement of elemols. All possible stereoisomers of elemol were synthesized. The structure of “epielemol” has to be revised.