W(CO)5(L)-catalyzed tandem intramolecular cyclopropanation/cope rearrangement for the stereoselective construction of bicyclo[5.3.0]decane framework

Utilizing the biscarbene character of electrophilically activated alkynes, a novel tandem intramolecular cyclopropanation/Cope rearrangement of 3-siloxy-1,3,9-trien-7-ynes catalyzed by W(CO)5(L) for the stereoselective construction of bicyclo[5.3.0]decane framework is achieved. When 3-siloxy-1,3,9-trien-7-ynes were treated with a catalytic amount of W(CO)6 under photoirradiation, bicyclo[5.3.0]decanes were obtained in good yield stereoselectively. In this reaction, the Cope rearrangement of the divinylcyclopropane intermediates, generated by the intramolecular cyclopropanation of 3-siloxy-1,3,9-trien-7-ynes based on the W(CO)5(L)-catalyzed electrophilic activation of alkynes, occurs to give synthetically useful functionalized bicyclo[5.3.0]decane derivatives stereoselectively.     

Synthesis of Si- and N-containing bicyclo[4.2.1]nona-2,4-dienes and bicyclo[4.2.1]nona-2,4,7-trienes

A [6π+2π] cycloaddition of Si- and N-containing alkynes and 1,2-dienes to cyclohepta-1,3,5-trienes in the presence of the two-component catalytic system (acac)₂TiCl₂-Et₂AlCl gives rise to the corresponding bicyclo[4.2.1]nona-2,4-diene and bicyclo[4.2.1]nona-2,4,7-triene derivatives.     

Three-component cycloadditions: the first transition metal-catalyzed [5+2+1] cycloaddition reactions

Prompted by our studies of transition metal-catalyzed [4+4], [4+2], [5+2], and [6+2] cycloadditions and by the view that these two-component reactions could be intercepted by a third component of one or more atoms, a new three-component transition metal-catalyzed cycloaddition is described. This new [5+2+1] cycloaddition proceeds in good to excellent yield and with high or complete regioselectivity with a variety of carbonyl-substituted alkynes to give bicyclo[3.3.0]octenone adducts, resulting from transannular closure of the intermediate eight-membered-ring cycloadduct. Effects of concentration, temperature, pressure, and catalyst loading on the efficiency of the reaction are discussed. This process provides access to complex building blocks for synthesis based on simple, readily available components.     

New reactions of carbon suboxide with alkynes

Synthesis of 3,4,7,8‐tetraalkyl‐2‐oxa‐bicyclo[4.2.0]octa‐1(6),3,7‐trien‐5‐ones( 4a‐d ),4,5,7,8‐tetraalkyl‐2‐oxa‐bicyclo[4.2.0]octa‐1(6),4,7‐trien‐3‐ones ( 6a‐d ) and 3,4,7,8‐tetraalkyl‐2H,5H‐cyclobuta[b]pyrano‐[2,3‐d]pyran‐2,5‐diones ( 7a‐d ) from the reaction of alkynes ( la‐d ) with carbon suboxide ( 2 ) in various molar ratios is described.     

Synthesis of Bicyclo[1.1.1]pentane Bioisosteres of Internal Alkynes and para‐Disubstituted Benzenes from [1.1.1]Propellane

We report a general preparation of arylated bicyclo[1.1.1]pentanes through the opening of [1.1.1]propellane with various arylmagnesium halides. After transmetalation with ZnCl₂ and Negishi cross‐coupling with aryl and heteroaryl halides, bis‐arylated bicyclo[1.1.1]pentanes are obtained. These bis‐arylated bicyclo[1.1.1]pentanes may be considered as bioisosteres of internal alkynes. Bioisosteres of tazarotene and the metabotropic glutamate receptor 5 (mGluR5) antagonist 2‐methyl‐6‐(phenylethynyl)pyridine were prepared and their physicochemical properties were evaluated.     

Isolable tris(alkyne) and bis(alkyne) complexes of gold(I)

Golden trefoils: Tris(alkyne)gold complex [(coct)(3)Au][SbF(6)] (see picture; 1-SbF(6)) can be synthesized from cyclooctyne (coct) and AuSbF(6) generated in situ. Treatment of AuCl with cyclooctyne led to the bis(alkyne)gold complex [Au(coct)(2)Cl] (2). DFT analysis indicates that the cyclooctyne ligands are net electron donors in 1 but overall electron acceptors in 2. AuSbF(6) is shown to mediate [2+2+2] cycloaddition reactions of alkynes.     

Ruthenium(II)-catalyzed cyclization of azabenzonorbornadienes with alkynes

The ruthenium-catalyzed cyclization of azabenzonorbornadienes with alkynes leads to an unanticipated dihydrobenzoindole framework. Depending on the structure of the alkyne and the Ru catalyst, either a dihydrobenzoindole and/or a [2+2] cycloaddition product could be formed. Cp*Ru(COD)Cl was found to be an active catalyst for the cyclization of an azabenzonorbornadiene with a propargylic alcohol to produce the dihydrobenz[g]indole as a single regio and stereoisomer in good yield. For other alkynes, selective formation of the dihydrobenz[g]indole is possible by using a cationic Ru catalyst, [Cp*Ru(CH3CN)3]PF6.     

Rhodium(I)-catalyzed [4+2+2] cycloadditions of 1,3-dienes, alkenes, and alkynes for the synthesis of cyclooctadienes

The first [4+2+2] cycloadditions involving terminal alkynes and diene-enes, including a fully intramolecular example, are reported resulting in the formation of cyclooctadienes using [RhCl(CO)2]2 (5 mol %) treated with AgSbF6 (10 mol %) as a precatalyst. The reaction is general for a variety of terminal alkynes, as well as variously substituted diene-enes (yields up to 88%).     

Cp*RuCl(COD) in catalysis: A unique role in the addition of diazoalkane carbene to alkynes

The catalytic transformations of functional alkynes with diazoalkanes in the presence of the catalyst precursor RuCl(COD)Cp* are presented. They show the unique role played by the Ru(X)Cp* moiety in catalysis and that the nature of the formed products strongly depends on the alkyne functionality. Simple alkynes generate dienes via double diazoalkane carbene addition to the triple bond. Enynes with terminal triple bond lead to alkenyl bicyclo[x.1.0]alkanes, including bicyclic aminoacid derivatives. 1,6-enynes with disubstituted propargylic carbon produce in priority alkenyl alkylidene cyclopentanes. 1,6-Allenynes offer the direct access to alkenyl alkylidene bicyclo[3.1.0]hexanes. Propargylic carboxylates lead to conjugated dienes by coupling of the diazoalkane carbene with the alkyne terminal carbon and 1,2-shift of the carboxylate. All catalytic reactions can be explained by the initial formation of the 16 electron RuCl(CHR)Cp* moiety giving first a 2+2 cycloaddition with the alkyne triple bond.     

Photochemical rearrangement approach to the total synthesis of (±)-pinguisone and (±)-deoxopinguisone

The total synthesis of (±)-pinguisone and (±)-deoxopinguisone, the unusual [5–6], fused-ring sesquiterpenes, was accomplished by the photochemical transformation of the bicyclo [3.2.2]non-6-en-2-one into the bicyclo [4.3.0]non-4-en-7-one.     

Tungsten(0)- and rhenium(I)-catalyzed tandem cyclization of acetylenic dienol silyl ethers based on geminal carbo-functionalization of alkynes

Tungsten(0)- and rhenium(I)-catalyzed reactions of acetylenic dienol silyl ethers based on the concept of geminal carbo-functionalization of alkynes are reported. Treatment of 3-siloxy-1,3-diene-7-ynes with catalytic amounts of [W(CO)(6)] or [ReCl(CO)(5)] under photoirradiation conditions gives synthetically useful bicyclo[3.3.0]octane derivatives in good yields. Extremely high catalytic activity is noted for the rhenium(I) complex. The reaction has been extended to substrates containing a nitrogen atom in their tethers. In this case, two kinds of synthetically useful heterocyclic compounds-the 2-azabicyclo[3.3.0]octane derivatives 9 and the monocyclic dihydropyrroles 10, with allenyl substituents-are obtained, and selective preparation of either product can be achieved through the use of an appropriate combination of the nitrogen substituent and the type of the rhenium(I) catalyst. The 2-azabicyclo[3.3.0]octane derivatives 9 are obtained selectively by carrying out treatment of N-Ns derivatives in the presence of [ReCl(CO)(4)(PPh(3))], whereas the dihydropyrrole derivatives 10 are obtained by treatment of N-Mbs derivatives with [ReCl(CO)(5)]/AgSbF(6) . Finally, we have applied this geminal carbo-functionalization to one-carbon-elongated substrates containing N-Ts moieties in their tethers. Selective 5-exo cyclization is achieved in the presence of gold(I) or rhenium(I) catalysts, whereas 6-endo cyclization is observed on use of [W(CO)(6)].     

Isomeric metamorphosis: Si3E (E = S, Se, and Te) bicyclo[1.1.0]butane and cyclobutene

Group 14 and 16 hybrid heavy bicyclo[1.1.0]butanes (tBu2MeSi)4Si3E (E = S, Se, and Te) 2a-c have been prepared by the [1 + 2] cycloaddition reaction of trisilirene 1 and the corresponding chalcogen. Bicyclo[1.1.0]butanes 2 have exceedingly short bridging Si-Si bonds (2.2616(19) A for 2b and 2.2771(13) A for 2c), a phenomenon explained by the important contribution of the trisilirene-chalcogen pi-complex character to the overall bonding of 2. Photolysis of 2a and 2b produced their valence isomers, the heavy cyclobutenes 3a and 3b, featuring flat four-membered Si3E rings and a planar geometry of the Si=Si double bond. The mechanism of such isomerization was studied using deuterium-labeled 2a-d6 to ascertain the preference of the pathway, involving the direct concerted symmetry-allowed transformation of bicyclo[1.1.0]butane 2 to cyclobutene 3.     

A Photochemical Approach to a Potential Precursor of the Bicyclo [6.4.0] Dodecane Ring System of Taxane Diterpenes

The intermolecular [2+2] photocycloaddition of dimedone 6 and 1-acetoxy-2-methyl-5-dioxolan-1-hexene 7 followed by alkaline treatment, gave the 1,5,5,11-tetramethyl-7-dioxolan bicyclo [4,3,2]-4-decen-2,3-dione 12, and the 1,5,5-trimethyl-3-hydroxy-7-dioxolan bicyclo [5,4,1] dodecan-2,11-dione 13.     

A novel chromium(0)-promoted four-component cycloaddition reaction

[formula: see text] Reaction of (eta 6-thiepin-1,1-dioxide)tricarbonylchromium(0) with excess terminal alkynes under photoactivation conditions affords novel pentacyclic adducts formally derived from a sequential [6 pi + 2 pi]/[6 pi + 2 pi]/[2 sigma + 2 pi] cycloaddition process.     

1-Bromobicyclo[1.1.0]butanes and strong bases: products and mechanism

Treatment of the bromobicyclo[1.1.0]butanes (=4)(=a) - (=c) with LDA led to the formation of the 1,2,3-butatrienes (=6) which were isomerized by excess base to the alkynes (=8). Reaction of [1-¹²-C](=4)(=c) with LDA afforded [3-¹²-C](=8)(=d), indicating that bicyclo[1.1.0]but-1(3)-ene (=5) was not an intermediate.     

Photochemistry of 3-substituted bicyclo[3.1.0]hex-3-en-2-ones. Regioselective synthesis of ortho-substituted phenols by Pauson-Khand reaction

[reaction: see text] 3-Substituted bicyclo[3.1.0]hex-3-en-2-ones 3, easily obtained by Pauson-Khand reaction between terminal alkynes and cyclopropene, have been quantitatively converted into ortho-substituted phenols 4 by irradiation with UV light (350 nm). The kinetics and mechanism of this photochemical process have been studied by means of FT-IR and semiempirical (AM1 3x3 CI) calculations.     

Expeditious synthesis of N-bridged heterocycles via dipolar cycloaddition of pentafulvenes with 3-oxidopyridinium betaines

A new and highly versatile approach towards the synthesis of bicyclo[6.3.0]undecanes and bicyclo[5.3.0]decanes was accomplished. The methodology adopted involved [6+3] and [3+2] cycloaddition reactions of pentafulvenes with 3-oxidopyridinium betaines generated either by the action of a base on the pyridinium salt or thermally from pyridinium betaine dimer. These well-functionalized bicyclo[6.3.0]undecanes and bicyclo[5.3.0]decanes offer a wide range of synthetic options, which can be expected to translate into a variety of rapid and efficient synthesis of natural products.     

First cobalt(I)-catalyzed [6 + 2] cycloadditions of cycloheptatriene with alkynes

[reaction: see text] The CoI2(dppe)/Zn/ZnI2 system effectively catalyzes the [6 + 2] cycloaddition of cycloheptatriene with terminal alkynes to afford 7-alkyl-bicyclo[4.2.1]nona-2,4,7-trienes in fair to excellent yields. The catalyst proved to be tolerant toward functional groups such as ketone, sulfone, ester, ketal, ether, alcohol, imide, and nitrile. The enantioselective cycloaddition of CHT and phenylacetylene with BINOL phosphoramidite ligand 4 afforded the cycloadduct 3a (R = Ph) in 91% yield and 74% ee.     

Synthesis of a novel series of tetracyclic opioid antagonists incorporating an 8-aminobicyclo[3.2.1]oct-6-ene sub-unit

The bridged bicyclo[3.2.1]oct-ene and -ane amines 9-13 have been prepared via [3+2]cycloaddition of allylic alcohols 6 to alkynes 7, and assessed as ligands at opioid receptors. Amine 10b is a potent antagonist at μ receptors.     

Lewis Acid Catalyzed Formal (3+2)-Cycloaddition of Bicyclo[1.1.0]butanes with Ketenes

Design, synthesis and application of benzene bioisosteres have attracted a lot of attention in the past 20 years. Recently, bicyclo[2.1.1]hexanes have emerged as highly attractive bioisosteres for ortho- and meta-substituted benzenes. Herein we report a mild, scalable and transition-metal-free protocol for the construction of highly substituted bicyclo[2.1.1]hexan-2-ones through Lewis acid catalyzed (3+2)-cycloaddition of bicyclo[1.1.0]-butane ketones with disubstituted ketenes. The reaction shows high functional group tolerance as documented by the successful preparation of various 3-alkyl-3-aryl as well as 3,3-bisalkyl bicyclo[2.1.1]hexan-2-ones (26 examples, up to 89 % yield). Postfunctionalization of the exocyclic ketone moiety is also demonstrated.