Synthesis of highly functionalized 2,5-disubstituted pyrrolidines via an aza-Morita-Baylis-Hillman-type reaction

An aza-Morita-Baylis-Hillman-type reaction of Michael acceptors with 5-substituted cyclic N,O-acetals derived from pyrrolidines has been investigated. It has been found that the combination of Me₂S and TMSOTf work well with unhindered and reactive enals and enones whilst the use of quinuclidine and TMSOTf is superior for more hindered Michael acceptors. The reactions lead to 2,5-trans-disubstituted pyrrolidines with good to excellent diastereoselectivity. The origin of the selectivity is discussed.     

Diastereoselective synthesis of β-aminocyclopentene sulfonic acid via hetero Diels-Alder reaction

A new cyclopentene GABA analogue was synthesized as a conformationally rigid analogue of the epilepsy drug vigabatrin. N-Sulfinyl dienophile Diels-Alder methodology, followed by alkaline hydrolysis of the corresponding dihydrothiazine oxide, oxidation and deprotection of the amino group gave cis-4-aminocyclopent-2-ene-1-sulfonic acid. The corresponding N,N-dimethylsulfinamide was also obtained.     

A novel group transfer polymerization of 1-trimethylsiloxy-benzocyclobutene via hetero Diels-Alder reaction

A novel group transfer polymerization via hetero-Diels-Alder reaction is described. When 1-trimethylsiloxybenzocyclobutene ( 1 ) was treated with a catalytic amount of p-anisaldehyde (4-methoxybenzaldehyde) and TASF (tris(dimethylamino)sulfonium difluorotrimethylsilanide) at room temperature for 0.5 h, poly[1,2-phenylene-1-(trimethylsiloxy)ethylene] was obtained quantitatively. The number-average molecular weight of the polymer was M̄_n = 2000 and the molecular weight distribution was narrow (ratio of weight-to number-average molecular weights M̄_w/M̄_n = 1.18). Structural characteristics suggested a polymerization mechanism involving isomerization of 1 to o-quinodimethane and successive hetero-Diels-Alder reaction leading to poly[1,2-phenylene-1-trimethylsiloxy ethylene]. The living-like nature of the polymerization was supported by a monomer addition experiment in which the molecular weight increased according to the increase of the added monomer.     

Synthesis of unsymmetrically 2,6-disubstituted 2,3-dihydrothiopyran-4-ones

A series of 2,3-dihydrothiopyran-4-one derivatives with unequal substituents in the 2- and 6-position have been prepared by double conjugate addition of sulfide to enynones. These starting materials were accessed in two steps from terminal alkynes and α,β-unsaturated aldehydes.     

Studies toward the biomimetic synthesis of tropolone natural products via a hetero Diels-Alder reaction

Analogues of the tropolone natural products pycnidione and epolone B were synthesized via a hetero Diels-Alder reaction of benzotropolone 10 with humulene. The quinone methide benzotropolone 13 was generated in situ by thermalisation of benzotropolone 10. Benzotropolone 10 was derived from phthalic acid via carbonyl ylide 8a followed by an intramolecular 1,3-dipolar cycloaddition and subsequent acid-catalyzed ring opening.     

Synthesis of 2,5-disubstituted pyrazolyl-1,3,4-oxadiazoles by the Huisgen reaction

Russian Chemical Bulletin - We developed an approach to the synthesis of 2,5-disubstituted pyrazole-containing 1,3,4-oxadiazoles by acylation of 5-(nitropyrazolyl)tetrazoles with alkyl, aryl, and...     

Stereoselective hetero Diels-Alder reaction of selenoaldehydes with pentavalent phosphole chalcogenides

Stereoselective hetero Diels-Alder reaction of selenoaldehydes, generated by thermal retro Diels-Alder reaction of anthracene cycloadducts, with pentavalent 3,4-dimethylphosphole chalcogenides at 110 °C in toluene to give the corresponding [4+2] cycloadducts as a single diastereoisomer in good yields, accompanied by a slight scrambling of chalcogen atoms. Higher reaction temperature led to an increase of the scrambling between chalcogen atoms.     

Kinetic study of the hetero Diels-Alder reaction in surfactant solutions

The kinetics of the cycloaddition of nitrosobenzene with 2,3-dimethyl-1,3-butadiene in solutions of anionic sodium di(2-ethyl-1-hexyl) sulphosuccinate (AOT) and cationic cetyltrimethylammonium bromide was investigated. The significant acceleration of the reaction rate by a factor of 5 compared to that in a pure ethylene glycol was observed. Isobaric activation parameters were determined, and the activation energy E _a was shown to decrease upon increasing AOT concentration in solutions with low surfactant concentrations.     

Synthesis of 3-halo-2,5-disubstituted furans via CuX mediated cyclization-halogenation reactions

The Cu(I) halide (X = I, Br, Cl) mediated reactions of Cbz-protected cis-2-phenylethenyl-3-hydroxypyrrolidine gave novel 3-halo-2,5-trisubstituted furans in good yields, via a cyclization-halogenation, ring-opening reaction sequence. In contrast, the reactions with CuCN gave mainly the corresponding 3-cyanofuro[3,2-b]pyrrole formed from a cyclization-cyanation reaction.     

Synthesis of 2,5-disubstituted 6-azaindoles from substituted aziridines via intramolecular cyclization

A new and efficient preparation of pharmacologically and biologically important 2,5-disubstituted 6-azaindoles was achieved from cyclizations of aziridin-2-yl dipropargylic alcohols as adducts of two propargyl groups to ethyl 1-benzylaziridine-2-carboxylate. The sequential cyclizations include pyrrole formation and a novel base-catalyzed intramolecular acetylenic Schmidt reaction.     

A concise formal total synthesis of mappicine and nothapodytine B via an intramolecular hetero Diels-Alder reaction

A six-step formal total synthesis of a natural alkaloid, mappicine (3), has been achieved. The highlight of our synthetic strategy is an intramolecular hetero Diels-Alder reaction that was used for the construction of the CD ring system of mappicine (3). In addition, it was demonstrated that the Sonogashira coupling reaction of 2-chloro-3-hydroxymethylquinoline (8c) with trimethylsilylacetylene proceeded at room temperature in excellent yield.     

Total synthesis of the alkaloids martinelline and martinellic acid via a hetero Diels-Alder multicomponent coupling reaction

[reaction: see text] A concise synthesis of the guanidine alkaloids, (+/-)-martinelline and (+/-)-martinellic acid, using a protic acid catalyzed 2:1 hetero Diels-Alder coupling reaction between N-Cbz 2-pyrroline and methyl 4-aminobenzoate, is described. Protic acid catalysis, rather than Lewis acid catalysis, was necessary to achieve the desired sense of diastereocontrol in the coupling reaction.     

Synthesis of (hetero)arylated pyridazin-3(2H)-ones via Negishi reaction involving zincated pyridazin-3(2H)-ones

Zincated pyridazin-3(2H)-ones generated via bromine-magnesium exchange followed by transmetalation using ZnCl(2) or via lactam-directed ortho C4-H zincation with TMPZnCl·LiCl have been synthesized. These in situ created organometallics can be used in Negishi reactions with iodo(hetero)arenes delivering a new approach toward (hetero)arylpyridazin-3(2H)-ones.     

Synthesis of 2,5-disubstituted pyrroles by the reaction of ketoximes with 1,2-dibromopropane

Conclusions The reaction of ketoximes with 1,2-dibromopropane in the KOH-DMSO system gave 2,5-disubstituted pyrroles in 21–56% yield.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2175–2177, September, 1988.     

Total synthesis of (+/-)-alantrypinone by hetero Diels-Alder reaction

An efficient total synthesis of (+/-)-alantrypinone 4 by hetero Diels-Alder reaction of a novel pyrazine diene 9 with either a functionalized 3-alkylideneoxindole or 3-methyleneoxindole itself is described. The Diels-Alder reactions provide both the desired regiochemistry and exo selectivity. An interesting anionic equilibration between alantrypinone 4 and its epimer 31 or between its ester analogues 23 and 24 has been demonstrated, and a mechanism has been proposed.     

Synthesis of novel 2,2-disubstituted naphthodioxoles via an unprecedented reaction

A reaction of 2,3-dihydroxynaphthalene with ethyl-2,3-dibromo-3-phenyl-propionate or 1,3-diaryl-2,3-dibromo ketone under basic conditions led to the formation of novel 2,2-disubstituted naphthodioxoles.     

Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement as an equivalent of the inverse electron demand hetero Diels-Alder reaction

A highly stereoselective formal inverse electron demand hetero Diels-Alder reaction (HDA) occurs on reaction of 2-aryl-alpha,beta-unsaturated aldehydes with cyclopentadiene. The major pathway for this transformation is shown to be a Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement.     

Synthesis of 2,5-disubstituted 3-iodofurans via palladium-catalyzed coupling and iodocyclization of terminal alkynes

2,5-Disubstituted 3-iodofurans are readily prepared under very mild reaction conditions by the palladium/copper-catalyzed cross-coupling of (Z)-β-bromoenol acetates and terminal alkynes, followed by iodocyclization. The useful intermediates conjugated enyne acetates are obtained in high yields in the transformation. Aryl- and alkyl-substituted alkynes undergo iodocyclization in good yields. The resulting iodine-containing furans can be readily elaborated to 2,3,5-trisubstituted furans.