Synthesis of carbazoles by dehydro Diels-Alder reactions of ynamides

A new approach to carbazoles and benzannulated carbazoles by means of intramolecular dehydro Diels-Alder of ynamides is reported. N-(o-Ethynyl)aryl ynamides and N-(o-ethynyl) arylynamides were prepared in a few steps starting from o-iodoaniline. Thermal cycloaddition of N-(o-ethynyl)aryl ynamides and N-(o-ethynyl) arylynamides affords carbazoles and benzannulated and heteroannulated carbazoles in moderate-to-good yields.     

Synthesis of the tetracyclic core of anthracycline antibiotics by an intramolecular dehydro Diels-Alder approach

[reaction: see text] A conceptually new approach to the tetracyclic core of the anthracycline antibiotics is reported. With use of this approach, the 7,8,9,10-tetrahydronaphthacene-5,12-dione skeleton has been synthesized in three steps, from commercially available reagents, in yields of up to 85%.     

Cyclic allene intermediates in intramolecular dehydro Diels-Alder reactions: labeling and theoretical cycloaromatization studies

A comprehensive theoretical and experimental investigation of dehydro Diels-Alder reactions examining the evolution of the cyclic allene intermediates under conditions for intramolecular and ionic and radical intermolecular cycloaromatization processes is reported. Theoretical calculations showed that the most favored intramolecular path for cycloaromatization of 1,2,4-cyclohexatriene 4 and its benzoannulated derivative 14, strained cyclic allenes, consists of a pair of successive [1,2] H shifts rather than a [1,5] shift. Cycloaromatization of cyclic allenes may follow both inter- and intramolecular pathways, depending on the experimental conditions (use of protic or aprotic solvents). For synthetic purposes, the best procedure is to use a protic solvent to promote the ionic intermolecular route, the fastest and highest yielding. When the reaction is carried out in CCl4, intermolecular radical addition of chlorine to the cyclic allene competes with intramolecular aromatization paths. Theoretical calculations predict a low barrier for the reaction of cyclic allenes with carbon tetrachloride, and that the cyclic allenes act as nucleophiles in this reaction.     

Synthesis of the zoanthamine ABC ring system: some surprises from intramolecular Diels-Alder reactions

[reaction: see text] In connection with the total synthesis of the marine alkaloids zoanthamine and norzoanthamine, an elaborate model study was conducted starting from (-)-carvone. In nine steps alkenyl iodides corresponding to the C11-C24 fragment of zoanthamine were obtained. The alkenyl iodides were coupled to various stannanes (C6-C10 fragment) via the Corey modification of the Stille reaction, affording a variety of Diels-Alder precursors. An interesting and highly unexpected cascade reaction sequence was observed during the screening of an intramolecular Diels-Alder reaction, generating a novel tetracyclic framework. A slight modification in the Diels-Alder precursor allowed the desired cycloaddition to take place, giving the cycloadduct in 87% yield.     

Synthesis of new tricyclic phosphines and phosphinites by intramolecular Diels-Alder reactions of trivalent phospholes

Phospholes bearing an allyl-X substituent at phosphorus tend to undergo an intramolecular Diels-Alder cycloaddition (IMDA) leading to the corresponding tricyclic derivative. When X = O or NR, the IMDA easily takes place at room temperature. When X = CH2, the IMDA slowly takes place around 110-140 degrees C, as a function to the substitution pattern of the dienic system. Two tricyclic derivatives (X = O and CH2) have been characterized by X-ray crystal structure analysis of the P-sulfides.     

Stereocontrol of intramolecular Diels-Alder reactions by an allylic diphenylcyclopropyl group

Intramolecular Diels-Alder reactions of ester-linked 1,3,8-nonatrienes carrying a diphenylcyclopropyl substituent attached to C1 proceed with high levels of stereoselectivity. The stereochemical outcomes of these reactions are explained by reference to B3LYP/6-31G(d) transition structures. Experimentally, the diphenylcyclopropane rings remain intact through these IMDA reactions, notwithstanding their predicted extremely high degree of asynchronicity (the B3LYP-computed lengths in the IMDA transition structures differ by as much as 1.1 angstroms), providing support to the notion that these reactions are concerted processes.     

beta-Acyloxysulfonyl tethers for intramolecular Diels-Alder cycloaddition reactions

[reaction: see text]. beta-Hydroxy sulfone-based tethers were employed for the first time to achieve thermally mediated intramolecular Diels-Alder cycloaddition. The reactions proceeded with complete regioselectivity and high (10/1) to complete endo/exo-selectivity and resulted in the preferential formation of one of the two possible endo-cycloadducts. The yields and stereoselectivities were proportional to the bulk of the R(1) substituent on the beta-acyloxysulfonyl tether.     

Asymmetric intramolecular Diels-Alder reactions of N-acyl-camphor-sultam trienes.

Treatment of triene-imides 4 with EtAlCl₂ at ?20° gave crystalline cycloadducts 5 which furnished enantiomerically pure bicyclic alcohols 9 with regeneration of the chiral auxiliary.     

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.     

Synthesis of ynamides from formamides

N-Formyl-tosylamides can be efficiently converted to N-ethynyl-tosylamides in two steps via the corresponding dichlorovinylamides.     

Siloxacyclopentenes as dienophile-linked directing groups in intramolecular Diels-Alder reactions

The synthesis and intramolecular Diels-Alder reactions of trienes 5 and 6 with a siloxacyclopentene-constrained dienophile are described. These reactions provide the primary cycloadducts 7 and 8 with high diastereoselectivity. These cycloadducts possess trans-relationships between the ring fusion proton and the adjacent C(1) alkoxy group and can be further elaborated to alcohols 9 and 11 (via protiodesilylation) or to 10 and 12 (via Fleming-Tamao oxidation) depending on the substitutent R.     

Enantioselective organocatalytic intramolecular Diels-Alder reactions: a computational study

The diastereo- and enantioselectivity obtained experimentally by Christmann in the amine-catalyzed intramolecular Diels-Alder reaction of α,β-unsaturated carbonylic compounds were fully rationalized using density functional theory methods at the PBE1PBE/6-311+G** level. A polarizable continuum model was used to describe solvent effects. The selectivity is induced in the cyclization step, and while the enantioselectivity results from the syn/anti orientation around the C-N enamine bond, the diastereoselectivity mainly results from the syn/anti configuration of the substituents in the forming cyclopentane ring. The remarkable reaction rate experimentally observed when an external protic acid is used is attributed to the strong decrease in the activation energy of all steps needed for the enamine formation, while the external acid marginally influences the cyclization step. When hydrogen-bond-donor catalysts are used, the formation of one hydrogen bond in the cyclization step inverts the configuration and reduces the selectivity. The different behavior between dialdehydes and ketoaldehydes is suggested to be resulting from different reaction rates in the catalyst elimination step.     

Intramolecular Diels-Alder and tandem intramolecular Diels-Alder/1,3-dipolar cycloaddition reactions of 1,3,4-oxadiazoles

The scope of intramolecular Diels-Alder and a novel tandem Diels-Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles is disclosed. In the cases examined, the tandem cycloadditions construct three new rings with formation of four new C-C bonds and set all six stereocenters about a central six-membered ring in a single step including three contiguous and four total quaternary centers without a trace of a second diastereomer.     

Synthesis of spirocyclopentene-indolines by intramolecular alkylidine insertion reactions

Intramolecular 1,5 CH insertion of unstabilized carbenes into the tertiary carbon of a substituted indoline generates spiro[cyclopent[2]ene-1,2′-indolines] in good yields and excellent enantioselectivities.     

Synthesis of cis-fused carbo-bicycles by domino enyne cross-metathesis/intramolecular Diels-Alder Reaction

A sequential combination of Ru-catalyzed enyne cross-metathesis (EYCM) and intramolecular Diels-Alder reaction (IMDA) is described. Different terminal alkynes and alpha,omega-dienes obtained by a Baylis-Hillman reaction were transformed into substituted cis-hexahydro-1H-indenes and cis-hexahydro-2H-naphthalin-1-ones.     

Highly diastereoselective synthesis of new indolopyrroloquinolines through intramolecular imino Diels-Alder reactions

A new, efficient and highly diastereoselective one-pot synthesis of cis-fused indolopyrroloquinoline derivatives is described through imino Diels-Alder reaction of substituted anilines or naphthylamines with N-prenylated-2-formyl-3-chloroindoles catalyzed by La(OTf)₃.     

Synthesis and Diels-Alder reactions of 4-vinylimidazoles

[structure in text] The synthesis of several 4-vinylimidazoles via Stille cross-coupling reactions of the corresponding protected 4-iodoimidazoles with tributylvinylstannane is described. These heterocyclic dienes are shown to be effective partners in the Diels-Alder reaction, providing adducts in good yield and exhibiting useful levels of isomer selectivity and stereoselectivity (endo/exo).     

Synthesis of bifluorenylidene-hinged crown ethers by intramolecular desulfur-dimerization reactions

Bifluorenylidene-hinged crown ethers are synthesized by the W(CO)₆-mediated intramolecular desulfur-dimerization of bridged bis-fluorenonedithioacetals.     

Chromone-3-carboxaldehydes in Diels-Alder reactions with indole-o-quinodimethane. Synthesis of tetrahydrochromeno[2,3-b]carbazoles

An efficient route to a new class of indole derivatives, tetrahydrochromeno[2,3-b]carbazoles, has been developed. The cycloaddition reactions of chromone-3-carboxaldehydes with indole-o-quinodimethane gave a diastereomeric mixture of Diels-Alder cycloadducts in good yields after in situ deformylation.