Annulation Products Research Articles

Synthesis of cyclic alkenyl ethers via intramolecular cyclization of O-alkynylbenzaldehydes. Importance of combination between CuI catalyst and DMF.

An efficient and remarkably general method for the synthesis of cyclic alkenyl ethers via the Cu(I)-catalyzed intramolecular cyclization of O-alkynylbenzaldehydes has been developed. The survey of metal catalysts and solvents revealed that the combination of copper(I) iodide and DMF was the catalytic system of choice. The reaction most probably proceeds via the nucleophilic addition of alcohols 2 to O-alkynylbenzaldehydes 1 to generate the corresponding hemiacetals, and subsequent nucleophilic attack of the hemiacetal oxygen to the copper coordinated alkyne would give the annulation products 3. In all cases, the reaction proceeded in a regiospecific manner leading to the six-membered endocyclic products via 6-endo-dig cyclization.

An Efficient Approach to Dihydrofurocoumarins via Palladium‐Catalyzed Annulation of 1,3‐Dienes by o‐Iodoacetoxycoumarins.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An efficient approach to dihydrofurocoumarins via palladium-catalyzed annulation of 1,3-dienes by o-iodoacetoxycoumarins.

The palladium-catalyzed annulation of 1,3-dienes by o-iodoacetoxycoumarins provides an efficient method for the synthesis of biologically interesting dihydrofurocoumarins. The presence of the acetyl group on the phenolic oxygen and the use of silver carbonate as a base are crucial for this process. This reaction is very general and regio- and stereoselective, and a wide variety of terminal, cyclic, and internal 1,3-dienes can be utilized. Derivatization of the annulation products provides an efficient approach to numerous analogues of natural products.

Cyclopentannulation on 3-phospholenes: an expedient route to the 2-phosphabicyclo[3.3.0]octene ring system

Treatment of 1-phenyl-3-phospholene derivatives with 2 equiv. of LDA followed by quenching the metallated intermediates with 1,3-dihaloalkanes affords 2-phosphabicyclo[3.3.0]oct-3-ene derivatives in good yield. The annulation reactions are highly regio- and stereoselective and lead to the formation of exo-Ph-P substituted products exclusively. Reduction of the resulting bicyclic phosphine oxides by phenylsilane gives the corresponding phosphines with complete retention of configuration at P. Application of this annulation procedure to acyclic allylic substrates leads to the corresponding monocyclic annulation products.

Development of the [3 + 2] Annulations of Cyclohexenylsilanes and Chlorosulfonyl Isocyanate: Application to the Total Synthesis of (.+‐.)‐Peduncularine.

The synthesis of (±)-peduncularine was accomplished using the [3 + 2] annulation of an allylic silane with chlorosulfonyl isocyanate to assemble the bicyclic core of the alkaloid. The stereochemistry of the annulation product was employed to control the installation of the indolylmethyl side chain at C-7 with complete stereoselectivity.

Development of the [3 + 2] Annulations of Cyclohexenylsilanes and Chlorosulfonyl Isocyanate: Application to the Total Synthesis of (±)-Peduncularine

The synthesis of (+/-)-peduncularine was accomplished using the [3 + 2] annulation of an allylic silane with chlorosulfonyl isocyanate to assemble the bicyclic core of the alkaloid. The stereochemistry of the annulation product was employed to control the installation of the indolylmethyl side chain at C-7 with complete stereoselectivity.

A highly stereoselective, novel coupling reaction between alkynes and aldehydes

In the presence of indium triflate or gallium chloride, a novel coupling between internal alkynes and aldehydes occurred to give unsaturated ketones and [4+1] annulation products.

Reactions of complex ligands: Part 94. Chromium-templated angular versus linear benzannulation of dibenzofuran and haptotropic metal migration in tetracyclic fused arenes

The chromium-templated [3+2+1]-benzannulation of dibenzofuryl(methoxy)carbene complex 1 with alkynes leads to hydroquinoid benzonaphthofurans. A competition of angular versus linear annulation affords angular-fused (η 6-1,2,3,4,4a,11c)-benzo[ b]naphtho[1,2- d]furan tricarbonyl chromium complexes 2– 6 along with considerable amounts of uncoordinated benzo[ b]naphtho[2,3- d]furans as linear annulation products 7– 9. As demonstrated for 2 and 6 the Cr(CO) 3 complexes undergo a thermally induced haptotropic metal migration along the tetracyclic heteroaromatic π-system to give (η 6-7a,8,9,10,11,11a)-benzonaphthofuran complexes 10 and 11 in which the chromium fragment is coordinated to the terminal unsubstituted benzoid ring. The molecular structures of both the kinetic annulation products and the thermodynamic rearrangement products were established by NMR spectroscopy and single crystal X-ray analysis.

Electrocyclic Ring Closure of the Enols of Vinyl Quinones. A 2H-Chromene Synthesis

Thermolysis of enolizable vinyl quinones in polar, aprotic media provides 2H-chromenes. Experimental evidence supports a two-step mechanism in which enolization is followed by a thermal 6pi-electrocyclic reaction of an intermediate quinone methide. Application of this method led to the total synthesis of the reputed structure of an Ageratum juvenile hormone. When enolizable vinyl quinones are the products of Stille coupling, the chromene annulation product is obtained directly. [reaction: see text]

An efficient synthesis of 3-trifluoromethylated 8-oxabicyclo[3.2.1]octa-2,6-dienes

The rhodium(II) acetate catalyzed decomposition of 3-trifluoromethylated vinyldiazomethanes 3 in the presence of furans resulted in the formation of a series of 3-trifluoromethylated 8-oxabicyclo[3.2.1]octa-2,6-dienes. The 4-substituent on the vinyldiazomethanes had great effects on the product distribution and the stereo- and regiochemistry of the [3+4] annulation products. The rhodium(II) acetate catalyzed reaction of 4-carbonyl substituted vinyldiazomethanes 3a– c with furans resulted in cyclopropenes and [3+4] annulation products, while in the case of cyano-substituted vinyldiazomethanes 3d, only cycloaddition products were obtained. The reaction was presumed to follow a tandem cyclopropanation/Cope rearrangement mechanism.

Asymmetric Synthesis of Homoallylic Amines and Functionalized Pyrrolidines via Direct Amino-Crotylation of In Situ Generated Imines

The asymmetric synthesis of functionalized homoallylic amines and silyl functionalized pyrrolidines through the Lewis acid promoted condensation of chiral ( E)-crotylsilanes with sulfonyl imines and in situ generated N-acyl imines is described. We had anticipated that this bond construction could be used in the asymmetric synthesis of the N-terminal amino acid subunit of the nikkomycins. Aryl sulfonyl imines condense with chiral silane reagents in the presence of BF 3·OEt 2 to form homoallylic arylsulfonyl amines with useful levels of syn selectivity. For cases involving aryl N-acyl imines we have learned that the temperature controls the course of the reaction. For instance, at temperatures of −78°C or below the major product is the pyrrolidine, while at higher temperatures (−30 to −20°C) the homoallylic amine is produced. For the cases studied, the [3+2]-annulation is limited to aryl imine derivatives, as alkyl- and branched- imines failed to produce the pyrrolidine derivatives: higher reaction temperatures promote the conversion of the annulation product to the homoallylic amines. In double stereodifferentiating reactions with in situ generated imines, good levels of selectivity were achieved in the formation of secondary amines bearing syn– anti and syn– syn stereochemical triads.

Solid-phase synthesis of 1,2,3,4-tetrahydro-2-pyridones via aza-annulation of enamines.

An efficient solid-phase approach has been developed to prepare nitrogen heterocycles with a 1,2,3,4-tetrahydro-2-pyridone core via aza-annulation of enamines. Immobilized enamines were prepared from the reaction of primary amines with propynoic acid derivatives or ketones. Aza-annulation reactions were carried out by reacting resin-bound enamines with symmetrical alpha,beta-unsaturated acid anhydrides or alpha,beta-unsaturated acids in the presence of DPPA and TEA. The annulation products were isolated in good to high crude yields. Influence of sterically hindered amines as well as alpha- and beta-substituted acrylic acid derivatives on the annulation reaction was also investigated.

A new cycloheptenone annulation method: use of the bifunctional reagent (Z )-5-iodo-1-tributylstannylpent-1-ene in organic synthesis

A new seven-membered annulation method that employs (Z)-5-iodo-1-tributylstannylpent-1-ene (1) as a key reagent and that is exemplified by the conversion of compounds 6, 12, 13, 20, 25, and 26 into the annulation products 11, 18, 19, 24, 33, and 34, respectively, is reported.

Nitro Compounds in the Double Annulation Route to Trans-Fused Bicyclic Compounds

Tethered carbon acids bearing nitro groups undergo a double Michael reaction with 3-butyn-2-one, and the cyclic products thereby obtained can be transformed into trans-fused bicyclic compounds with high levels of substitution and functionality. Three new C−C or C−N bonds, two new rings, two to four new stereocenters, and one or two new quaternary centers are created in this novel double annulation of two acyclic, readily available starting materials. Examples of the synthesis of trans-decalins, trans-hydrindanes, and trans-perhydroindoles are presented. Methods for converting the nitro groups in the double Michael and double annulation products into other groups are also described.

Novel annulation products derived by selective attack on the C(18) angular methyl group of the cardenolide ouabain

Selective reactions at the C(18) angular methyl group of ouabain derivatives employing rhodium- and photochemically-mediated CC bond formation allow the synthesis of annulation products 4 and 13.

Synthesis and reactivity of Michael adducts of cyclic β-ketoesters enolates with electrophilic acetylenes

The enolates of cyclic β-ketoesters react with electrophilic acetylenes to give the corresponding Michael adducts in good yields when the reaction is performed in acetone in the presence of catalytic amounts of K 2CO 3. The Michael adducts resulting from ethynylmethylketone, when refluxed in toluene in the presence of catalytic amounts of pTsOH, undergo an intramolecular aldol reaction leading mainly to bicyclo [n. 3. 1]alkadienones besides Robinson annulation products.

3 + 4] Annulation of α,β-Unsaturated Acylsilanes with Enolates of α,β-Unsaturated Methyl Ketones: Scope and Mechanism

Reactions of the E and Z isomers of (β-(trimethylsilyl)acryloyl)(tert-butyl)dimethylsilanes with lithium enolate of α,β-unsaturated methyl ketones at −80 to −30 °C afford cis-5,6- and trans-5,6-disubstituted 3-cyclohepetenones, respectively. The same [3 + 4] annulation is observed in the reaction of (β-(tri-n-butylstannyl)acryloyl)silanes. The annulation products are readily transformed into 4-cycloheptene-1,3-dione by treatment with NBS or mCPBA. The observed stereospecificity in the annulation is explained by the reaction pathway that involves an anionic oxy-Cope rearrangement of 1,2-divinylcyclopropanediol intermediate generated via Brook rearrangement of the 1,2-adduct of a lithium enolate. Isolation of vinylcyclopropanol derivative from the reaction of (β-(tri-n-butylstannyl)acryloyl)silanes with lithium enolate of 2‘-bromoacetophenone and its transformation into cycloheptenone derivative with LDA provide strong support for the proposed mechanism. Further support is obtained from the reactions of 1,2...

An Unusual Cyclopentaannulation Reaction: Thermolysis of an α,β-Unsaturated Fischer Carbene Complex Anchored on a Fe2(CO)6(μ-Se)2 Core

An unusual annulation of a Fischer carbene complex anchored on a Fe2(CO)6(μ-Se)2 core is examined. Thermolysis of Fe2(CO)6{μ-SeC(Ph)C(Se)[(OEt)CCr(CO)5]} in THF yields an unusual annulated product, [Fe2(CO)6Se2{μ-(CO)3Cr(η5-C5H(CH2Ph)(Ph)(OEt))}] (1), as characterized by IR and 1H, 13C, and 77Se NMR spectroscopies, and its structure has been established by single-crystal X-ray diffraction.

Aluminum Chloride Catalyzed Stereoselective [3 + 2] Cycloaddition of Allylsilanes with Simple Conjugated Dienes

Allyltrimethylsilane reacts with simple conjugated dienes in the presence of aluminum chloride catalyst to give stereoselective [3 + 2] cycloadducts of trans-vinylcyclopentanes in 29−72% yields at −10 °C. The same reactions give 1,4-allylsilylated compounds as the major products at −50 °C, which cyclize to the annulation products as the reaction mixture is allowed to warm to −10 °C. The reaction using (2-methyl-2-propenyl)trimethylsilane instead of allyltrimethylsilane does not give the annulation due to an unfavorable 1,2-silyl shift but, rather, allylsilylation products. The results are consistent with an initial 1,4-allylsilylation of the conjugated diene, followed by the intramolecular cyclization of the 1,4-allylsilylated alkene to the stereoselective trans-[3 + 2] cycloadduct, via a 1,2-silyl shift.

3 + 2] Annulation of Allylidenetriphenylphosphorane with 1,2-Diacylethylenes and 1,2-Diacylacetylenes: A One-Step Synthesis of Tri- and Tetrasubstituted Cyclopentadienes and Fulvenes

Allylidenetriphenylphosphoranes underwent [3 + 2] annulation with 1,2-diacylethylenes at room temperature to give cyclopentadienes 11−17 having various substituents except for (Z)-3-acetylacrolein (18) which gave cyclohexadiene 19 derived from [3 + 3] annulation as the sole annulation product. The resulting cyclopentadienes were mixtures of the corresponding double-bond isomers which arose through an equilibrium process from the initially formed 1,3-dienes a under the weakly basic reaction conditions. Similar reactions of the phosphoranes with 1,2-diacylacetylenes afforded substituted fulvenes 24, 25, and 28 directly without the attendant formation of the corresponding benzene derivatives which come from another possible [3 + 3] annulation. The observed high level of the preference for the [3 + 2] annulation is discussed on the basis of the semiempirical PM3 MO calculations. The calculations suggested that the course of the annulation may be kinetically controlled at the oxaphosphetane-forming step of the...