Stereo‐ and Regioselective Synthesis of Tricyclic Spirolactones by Diastereoisomeric Differentiation of a Collective Key Precursor

A general, parallel, and collective synthesis of 5/5/5‐ and 5/5/6‐ring fusion topologies of tricyclic spiranoid lactones through the controlled cyclizations of easily accessible, common key precursors is described. The rapid composition of key cycloalkyl methylene precursors yielded an assembly of bicyclic diastereoisomeric iodolactones, which were individually converted into a wide range of tricyclic, angularly fused spiranoid lactones in a regioselective and stereodirected fashion through the diastereoisomeric differentiation of a collective key precursor. The critical stereochemical assignment of the bicyclic starting materials, as well as the tricyclic targets, was confirmed by X‐ray crystal structure determination.     

Studies of Intramolecular Cyclization of 4-Arylpyridines. II Syntheses of Condensed Tricyclic Pyridines

A convenient method for the synthesis of condensed tricyclic pyridines using intramolecular cyclization of 4-arylpyridines is reported. The tricyclic compounds, 2-azafluorenone (9), 2-azafluorenone (10), 2-azafluorenol (11), lactones 12 and 13, and anhydride 14 have been prepared.     

Samarium(II) iodide-mediated intramolecular conjugate additions of alpha,beta-unsaturated lactones

Samarium(II) iodide, in the presence of catalytic amounts of nickel(II) iodide, has been used to promote intramolecular conjugate additions of alkyl halides onto alpha,beta-unsaturated lactones. This process has been shown to be applicable to a number of alpha,beta-unsaturated lactones, including tetrasubstituted olefins, and has been demonstrated to be quite general for the formation of saturated bicyclic and tricyclic lactones. The method presented herein provides a mild, efficient process to form structurally complex lactones from simple precursors.     

Reactions selectives des organonagnesiens avec les lactols et les lactones. Synthese des diols primaires-secondaires

The reactionz of organomagnesium compounds with cyclic lactols and the phthalde show a high chemioselectivity and provide respectively corresponding monoalkylated cyclic lactones and diols We also observe that the formation of bridged tricyclic lactones stereoselectively yields to thetransisomer. In the same way, we describe an easy and general method for the synthesis of diols, precursors of dibromides and cyclic ethers.     

General approach for the stereocontrolled synthesis of tricyclic lactones via allene intramolecular cycloaddition. An application to the synthesis of (±)-platyphyllide

A new synthesis of tricyclic lactones via allene intramolecular cycloaddition and its application to synthesis of (±)-platyphyllide are described.     

Acid-catalyzed rearrangement of fused alkylideneoxetanols

Complex aza-fuzed tricyclic lactones are obtained in a two-step photochemical cycloaddition/acid-catalyzed rearrangement of simple alkoxy maleimide derivatives. The sequence involves a complex acid-catalyzed skeletal rearrangement of the intermediate alkylideneoxetanols.     

Stereoisomeric carboxamides of the bicyclo[2,2,1] heptene series in the epoxidation reaction

The epoxidation of isomeric carboxamides of the bicyclo[2,2,1]heptene series has been studied; in the case of exo-carboxamides it leads to expoxides, and in the case of endo-carboxamides to tricyclic lactones.     

Synthesis of Unsaturated Tricyclic Lactones. The Coupling of the Enol Triflate of β-Keto Lactones with Lithium Dimethylcuprate

The anions of selected β-keto lactones were transformed into their corresponding enol triflates. These enol triflates were coupled with lithium dimethylcuprate to afford tricyclic unsaturated /aciones, key intermediates for the synthesis of the biologically important natural product forskolin.     

Stereoselective pig liver esterase-catalyzed hydrolysis of rigid bicyclic meso-diesters: Preparation of optically pure 4,7-epoxytetra- and hexa-hydrophthalides.

The bicyclic and rather rigid meso-diesters 1 - 3 have been found to be good substrates for pig liver esterase. The half-esters obtained have been converted to either one of the enantiomers of tricyclic lactones, of potential value for natural product synthesis.     

Intramolecular Photocyclization of 2‐Acylphenyl Methacrylates: a Convenient Access to 4,5‐Dihydro‐1,4‐epoxy‐2‐benzoxepin‐3(1H)‐ones (= Benzo[c]‐6,8‐dioxabicyclo[3.2.1]octan‐7‐ones

The photochemical reactions of 2‐acylphenyl methacrylates (= 2‐acylphenyl 2‐methylprop‐2‐enoates) 1 were investigated. Irradiation of 2‐acylphenyl methacrylates 1a – d in MeCN gave the tricyclic lactones 2a – d in good yields, together with a small amount of O CO bond cleavage product, the 2‐acylphenols 3a – d (Scheme 2, Table). The formation of the tricyclic lactones 2 probably follows a mechanism involving a 1,7‐diradical through ζ‐H abstraction (1,8‐H transfer) by the excited carbonyl O‐atom (Scheme 3). Irradiation of 2‐acylphenyl tiglate (= 2‐acylphenyl (2E)‐2‐methylbut‐2‐enoate) 1e and 2‐acylphenyl methacrylates 1g – i , substituted by a MeO group (δ‐H) at the 3,5‐positions of the phenyl group, also gave the tricyclic lactones 2e and 2g – i , but in low yields. On the other hand, no H‐abstraction products were observed on irridation of 2‐(ethoxycarbonyl)phenyl methacrylate 1f , of 2‐acylphenyl methacrylate 1j which is substituted by a Me group (γ‐H) at the 3,5‐positions of the phenyl group, and of 1k with an OH group at the 3‐position of the phenyl group.     

A stereoselective approach to optically active butenolides by Horner–Wadsworth–Emmons olefination reaction of α-hydroxy ketones

Di- and trisubstituted butenolides and tricyclic unsaturated lactones, of high enantiomeric excess were prepared via the efficient sequential esterification Horner–Wadsworth–Emmons reaction of enantiomerically enriched 2-hydroxy-substituted phenones and aromatic cyclic α-hydroxy ketones in good yield.     

Concise enantiodivergent synthesis of (+)- and (−)-trans-quercus lactones

A concise enantiodivergent total synthesis of (+)- and (−)-quercus lactones from the known tricyclic lactone (+)-1 as a single chiral template was achieved using the diastereoselective nucleophilic addition of organometallic reagents as the key step.     

The furan approach to azacyclic compounds

We describe an efficient new approach to the synthesis of azacyclic compounds that extends our recently developed methodology based on the oxidation of a furan ring with singlet oxygen followed by an intramolecular hetero Michael addition. The new approach gives access to the readily opened bicyclic lactones and novel tricyclic heterocycles containing the piperidine ring.     

Intramolecular reductive ketone-alkynoate coupling reaction promoted by (η2-propene)titanium

Intramolecular reductive coupling of cycloalkanones tethered to alkynoates in the presence of (η(2)-propene)titanium was successfully performed to provide hydroxy-esters in a diastereoselective manner. Subsequent lactonization afforded angularly fused unsaturated tricyclic lactones which represent relevant substructures of numerous bioactive compounds.     

Lactone-directed intramolecular Diels-Alder cyclization: synthesis of trans-dihydroconfertifolin

Trienes 1 and 3 were obtained in five steps from ethyl 4-acetoxy-3-oxobutanoate and 6-iodo-3-methyl-1,3-hexadiene. Intramolecular Diels-Alder cyclization of 1 and 3 gave tricyclic lactones 2 and 4 as the major products, respectively. The key intermediate 4 was converted in two steps to trans-dihydroconfertifolin (5).     

Enantio- and diastereocontrolled synthesis of (-)-iridolactone and (+)-pedicularis-lactone

[structure: see text]. Two iridoid lactones, (-)-iridolactone and (+)-pedicularis-lactone, have been synthesized in an enantio- and diastereocontrolled manner starting from a tricyclic chiral building block serving as a synthetic equivalent of chiral 3-(hydroxymethyl)cyclopenta-2,4-dien-1-ol.     

Reductive cleavage and subsequent transformations of 5-oxa-6-azaspiro[2.4]heptane-1-carboxylates

Treatment of methyl 4,6-diaryl-5-oxa-6-azaspiro[2.4]heptane-1-carboxylates with zinc in acetic acid leads to cleavage of the N–O bond in the isoxazolidine ring with formation of 1,3-amino alcohols whose subsequent cyclization under the reaction conditions yields bi- or tricyclic lactams or lactones with retention of the three-membered ring.     

Volvalerelactones A and B, two new sesquiterpenoid lactones with an unprecedented skeleton from Valeriana officinalis var. latifolia

Volvalerelactones A and B (1 and 2), two new sesquiterpenoid lactones with an unprecedented 3/7/6 tricyclic ring system, were isolated from the roots of Valeriana officinalis var. latifolia. Their structures and relative configurations were elucidated by spectroscopic data and single-crystal X-ray diffraction crystallography, and the absolute configuration was assigned by computational methods. The possible biosynthetic pathways of 1 and 2 were also proposed.     

Complementary diastereoselective reduction of cyclic gamma-keto acids: efficient access to trisubsituted gamma-lactones

Complementary reduction conditions have been identified that provide ready access to each respective diastereomer of bi- and tricyclic, trisustituted gamma-lactones starting from the corresponding cyclic gamma-keto acids. Subjection of cyclic gamma-keto acids to silane reagents in the presence of trifluoroacetic acid provides all syn-gamma-lactones, while reduction with trialkylborohydrides furnishes the syn,anti-gamma-lactones. The conditions are mild and provide the product lactones in good yields and modest to excellent selectivity.     

The diastereoselective synthesis of functionalised spirocyclic lactams and lactones using a Cope elimination/intramolecular nitrone cycloaddition strategy

Functionalised hydroxylamine derivatives of (S)-proline and pipecolic acid have been prepared using a Cope elimination. These hydroxylamines have been found to undergo oxidation to the nitrone either in the presence of air or a catalytic quantity of TPAP. An intramolecular 1,3-dipolar cycloaddition then occurs between the nitrone and pendant double bond to give tricyclic lactams and lactones with high diastereoselectivity.