Diastereoselective intermolecular Pauson-Khand reactions of chiral cyclopropenes

In this Letter, it is demonstrated that the unusual reactivity of cyclopropenes can increase the scope and utility of intermolecular Pauson-Khand reactions. The well-defined chiral environment of cyclopropenes has a powerful influence on the diastereoselectivity of the reactions and leads to the production of a single cyclopentenone in each of the described cases. The cyclopropane ring strongly influences the stereochemistry of reactions at the enone, and the three-membered ring can subsequently be cleaved under mild conditions. [reaction: see text]     

Arene-chromium tricarbonyl complexes in the Pauson-Khand reaction

[reactions: see text] We show the use of arene-chromium tricarbonyl complexes in intra- and intermolecular Pauson-Khand reactions. Both styrene and ethynylbenzene complexes react with alkynes and olefins. The synthesis of enynes connected through chromium-complexed aromatic rings is developed. The intramolecular Pauson-Khand reaction occurs in a totally diastereoselective manner.     

Advances in the Pauson-Khand reaction: development of reactive cobalt complexes

Three conceptually new methods employing reactive cobalt carbonyl complexes have been developed for the Pauson-Khand reaction. The first method involves activation of alkyne-dicobalt hexacarbonyls with "hard" Lewis bases. Primary amines dramatically promote the stoichiometric Pauson-Khand reaction. The active cobalt complexes produced in the system exhibit high reducing ability. The second method involves activation of dicobalt octacarbonyl with less electron-donating "hard" Lewis bases such as 1,2-dimethoxyethane and water. These Lewis bases were successfully utilized as a promoter for the catalytic Pauson-Khand reaction. The third method employs methylidynetricobalt nonacarbonyl cluster, which exhibits high reactivity in the catalytic Pauson-Khand reaction in the absence of activator. This may be due to facile coordination of the substrate to the metal center through dissociative and associative mechanisms and/or cleavage of one of the cobalt-cobalt bonds.     

Carbonylative dimerisation of norbornene by cobalt carbonyl: an overlooked by-product of the Pauson-Khand reaction

Treatment of norbornene with either dicobaltoctacarbonyl or with preformed alkyne-dicobalthexacarbonyl complexes gives enol-lactone dimer 3, derived from carbonylative coupling of two molecules of norbornene. This product which has not been recorded before under these conditions appears likely to be an overlooked by-product of many Pauson-Khand reactions.     

Regiochemistry of S-alkyl-substituted alkynes in Pauson-Khand reactions. Is a correlation with X-ray data and charge distribution calculations of the Co(2)(CO)(6)-alkyne complexes possible?

[reaction: see text] Pauson-Khand reactions (PKR) of RSCtbd1;CR' (6-10) yielded in all cases as the main product the regioisomer with the alkyl-S group disposed alpha to the CO group (16a-22a). Correlation of these results with X-ray data and charge distribution calculations of the corresponding dicobalthexacarbonyl complexes proves that a recently postulated "trans effect" in these complexes is not suitable for predicting the regiochemical outcome of the PKR unambiguously.     

Aqueous-phase, thermal Pauson-Khand reactions in the presence of surfactants

Efficient stoichiometric Pauson-Khand reactions were realized in water as the only solvent, and in the presence of surfactants as additives. Use of the cationic surfactant CTAB provided good yields of cyclopentenones from the thermal reactions of pre-formed dicobalthexacarbonyl complexes of enynes and alkynes. The water-CTAB medium was found to be less effective with Co₄(CO)₁₂ as the promoter of the reaction. Incidentally, these results have provided a strictly water-based PKR protocol under very mild and convenient conditions.     

Low-energy pathway for pauson-khand reactions: synthesis and reactivity of dicobalt hexacarbonyl complexes of chiral ynamines

A family of dicobalt hexacarbonyl complexes of 1-(dialkylamino)-2-(trimethysilyl)acetylenes (3a-f) derived both from achiral and chiral amines [a, morpholine; b, (S)-2-methoxymethylpyrrolidine; c, (2R,5R)-2, 5-bis(methoxymethyl)pyrrolidine; d, (+/-)-trans-2, 5-bis(benzyloxymethyl)pyrrolidine; e, (2R,5R)-2, 5-dimethylpyrrolidine; f, (S)-(alpha-methylbenzyl)benzylamine] has been prepared by a one-stage process from dichloroacetylene. The methanolysis at room temperature of these complexes (MeOH/K(2)CO(3)) induces the selective cleavage of the carbon-silicon bond, leading to the thermally unstable terminal ynamine complexes 12a-f. The Pauson-Khand reaction of 12a-f with strained olefins (norbornadiene and norbornene) takes place at unprecedentedly low temperatures (-35 degrees C) in the absence of chemical promoters. Diastereoselectivities of up to 94:6 are recorded in these reactions with the ynamine complexes derived from C(2) symmetrical chiral auxiliaries (12c,d). The high reactivity depicted by terminal ynamines in the Pauson-Khand reaction has been analyzed by theoretical semiempirical procedures [PM3(tm)] and with density functional theory (VWN/B88), and appears to reflect an easy CO loss from the ynamine-dicobalt hexacarbonyl complexes.     

Cyclopropenes in the 1,3-dipolar cycloaddition with carbonyl ylides: experimental and theoretical evidence for the enhancement of sigma-withdrawal in 3-substituted-cyclopropenes

The carbonyl ylide dipoles generated by the dirhodium tetra-acetate-catalyzed decomposition of diazocarbonyl precursors 1, 5, and 8 cycloadd to 3-substituted 1,2-diphenylcyclopropenes 3a-e and 3,3-disubstituted cyclopropenes 13, 14, 19, and 20 to give polycyclic compounds with 8-oxatricyclo[3.2.1.0(2,4)]octane and 9-oxatricyclo[3.3.1.0(2,4)]nonane frameworks. Generally, reactions proceed stereoselectively to give adducts of exo stereochemistry with the approach of the carbonyl ylide dipoles from the less-hindered face of cyclopropenes. The electronic properties of the substituent at the C3 position of cyclopropenes play an important role in governing the reactivity of cyclopropenes: when the C3 position is substituted by electron-acceptors such as the methoxycarbonyl or cyano groups, the yields of adducts are decreased significantly or no adducts can be detected at all. Relative reactivities of cyclopropenes were quantified by competition experiments to give the best correlation with sigmaF-Taft constants. Both measured photoelectron spectra and ground-state calculations of a series of 1,2-diphenylcyclopropenes indicate considerable lowering of cyclopropene pi-HOMO energies by substitution with an acceptor group. Such changes in electronic structures of cyclopropenes may cause the inversion of frontier molecular orbital (FMO) interactions from HOMO(cyclopropene)-LUMO(ylide) to LUMO(cyclopropene)-HOMO(ylide) type. In terms of philicity, nucleophilic properties of acceptor-substituted cyclopropenes are diminished to such an extent that these species are no longer good nucleophiles in the reaction with carbonyl ylides, and neither are they good electrophiles, being unreactive. This was shown by the B3LYP calculations of addends.     

Synthesis of tricyclic aromatic compounds by the intramolecular pauson-khand reaction promoted by molecular sieves(,)(1)

Pauson-Khand reactions are carried out with different substituted aromatic enynes, yielding tricyclic cyclopentenones related to natural products such as chromenes. Enynes are easily obtained in a two-step approximation from the corresponding salicylaldehydes. The reaction is promoted by dissolved TMANO (trimethylamine N-oxide) and/or 4 A molecular sieves. This new way of induction for the Pauson-Khand reaction increases yields remarkably, allowing the reaction of some substituted alkenes which fail to react in the absence of the zeolite. Isomerization of the double bond of the cyclopentenone ring is observed except when nonterminal triple bonds are used. For trisubstituted alkenes, an interrupted Pauson-Khand process is observed with moderate yields.     

A sub-stoichiometric tungsten-mediated Pauson-Khand reaction: Scope and limitations

Terminal alkynes do not partake in sequential [2+2+1]/benzoannulation reactions with Fischer carbene complexes and highly reactive and sterically hindered olefins; instead, they undergo a Fischer carbene complex-catalyzed Pauson-Khand reaction (PKR). This result has allowed the development, for the first time, of a tungsten-catalyzed PKR, although of limited scope.     

Recent developments of cyclopropene chemistry

This critical review discusses recent developments in the field of cyclopropene chemistry. Although several excellent reviews that mainly focused on the thermolysis and pyrolysis as well as metal-mediated reactions of cyclopropenes have been published, significant new developments have also been achieved in recent years. This brand new review provides an overview of the progress from 2007 to 2011 on the syntheses and transformations of cyclopropenes as well as their related mechanistic studies (238 references).     

Stereoselective total syntheses of three Lycopodium alkaloids, (-)-magellanine, (+)-magellaninone, and (+)-paniculatine, based on two Pauson-Khand reactions

The total syntheses of (-)-magellanine, (+)-magellaninone, and (+)-paniculatine were completed from diethyl l-tartrate via the common intermediate in a stereoselective manner. The crucial steps in these syntheses involved two intramolecular Pauson-Khand reactions of enynes: the first Pauson-Khand reaction constructed the bicyclo[4.3.0] carbon framework, the corresponding A and B rings of these alkaloids in a highly stereoselective manner, whereas the second Pauson-Khand reaction stereoselectively produced the bicyclo[3.3.0]skeleton, which could be converted into the C and D rings of the target natural products.     

Enantioenriched synthesis of cyclopropenes with a quaternary stereocenter, versatile building blocks

Ir(salen) complexes were found to catalyze enantioselective cyclopropenation efficiently. Cyclopropenation can be carried out using either a donor/acceptor- or an acceptor/acceptor-substituted diazo compound such as α-aryl-α-diazoacetates, α-phenyl-α-diazophosphonate, 2,2,2-trifluoro-1-phenyl-1-diazoethane, and α-cyano-α-diazoacetamide as carbenoid precursors. The reactions provide highly enantioenriched cyclopropenes (84-98% ee) with a functionalized quaternary carbon as versatile building blocks.     

Synthesis and thermolysis of tetrasubstituted cyclopropenes

Photolysis of 5-benzyl-2-methoxy-2,5-dimethyl-³-1, 3,4-oxadiazoline and of the 5,5-dibenzyl analogue with 300-nm light afforded 1-phenyl-2-diazopropane and 1,3-diphenyl-2-diazopropane, respectively. The diazoalkanes were intercepted, in situ, with dimethyl acetylenedicarboxylate to afford 3-benzyl-4,5-bis(methoxycarbonyl)-3-methyl-3H-pyrazole and 3,3-dibenzyl-4,5-bis(methoxycarbonyl)-3H-pyrazole, respectively. Those pyrazoles are short-lived under the reaction conditions and undergo two major reactions. Photolysis prior to rearrangement affords the corresponding 3,3-dialkyI-1,2-bis(methoxycarbonyl)-cyclopropenes. Thermal 1,5-benzyl migration converts the two 3H-pyrazoles in part into the corresponding 4H-pyrazoles, which undergo photolysis to 2,3-dialkyl-1,3-bis(methoxycarbonyl)cyclopropenes.Thermolysis of the 3,3-dialkyl-1,2-bis(methoxycarbonyl) cyclopropenes affords conjugated dienes, presumably through the sequence cyclopropene vinyl carbene diene. The stereochemistry of the dienes was determined and a mechanism consistent with that stereochemistry is proposed.The 2,3-dialkyl-1,3-bis(methoxycarbonyl)cyclopropanes are very stable under conditions that convert isomeric 3,3-dialkyl-1,2-bis(methoxycarbonyl)cyclopropenes to conjugated dienes. It is proposed that the effect of substitution pattern on the thermolysis rate constants is the result of combined ground state and transition state factors.     

Diversity oriented synthesis of tricyclic compounds from glycals using the Ferrier and the Pauson-Khand reactions

Diversity oriented synthesis of tricyclic compounds was achieved using a combination of the Ferrier reaction and the Pauson-Khand reaction. Ferrier reaction was effected using NbCl5, and the Pauson-Khand reaction was carried out using Co2(CO)8, acetonitrile-dimethoxyethane. Michael additions using various alkyl, aryl, and heterocyclic thiols were also performed successfully. The Ferrier, Pauson-Khand, and Michael addition reactions were found to be highly diastereoselective.     

Reversing the stereoselectivity of the intermolecular Pauson-Khand reaction: formation of endo-fused norbornadiene adducts

[reaction: see text] An unprecedented endo-selective and regioselective intermolecular Pauson-Khand reaction takes place when heterobimetallic (Mo-Co) complexes derived from N-(2-alkynoyl)oxazolidinones or sultams are heated in the presence of norbornadiene.     

The organometallic chemistry of nitrogenases

Nitrogenases mediate the reduction of many substrates other than dinitrogen and a summary is given. Several chemical systems that mimic aspects of nitrogenase reactivity, including transition metal complexes of alkynes and olefins, are outlined. Their protonation has been studied and their relevance to reduction of alkynes and olefins by nitrogenase is assessed. Cyclopropene is reduced by molybdenum nitrogenase to propene and cyclopropane. The reactions of cyclopropene with different transition metal complexes are discussed and a study of interactions of cyclopropenes with models for the active site of the nitrogenase enzyme are described. These models include transition metal hydrides, such as [FeH(H₂)(dmpe)₂][BPh₄] and [MoH₄(dppe)₂] reducing 3,3-dimethylcyclopropene and cyclopropene. Products observed upon protonation and deuteration of several platinum-cyclopropene complexes are presented and a mechanism for their formation is proposed.     

Synthesis of stable derivatives of cycloprop-2-ene carboxylic acid

Large-scale syntheses of 3-(cycloprop-2-en-1-oyl)oxazolidinones from acetylene and ethyl diazoacetate are described. Unlike other cyclopropenes that bear a single substitutent at C-3, these compounds are stable to long-term storage. Although the cyclopropene derivatives are unusually stable, they are reactive toward cyclic and acyclic dienes in stereoselective Diels-Alder reactions.     

Asymmetric intramolecular pauson-khand reaction mediated by a remote sulfenyl or sulfinyl group

In this work, we report the use of the asymmetric intramolecular Pauson-Khand reactions of 4-aryl-4-cyano-1,6-enynes for obtaining enantiomerically enriched bicyclo[3.3.0]octenones, and the influence of both the quaternary stereocenter and the sulfur functions located at ortho-position of the aryl group, on their stereoselectivity and reactivity. The sulfenyl derivatives bearing substituted or unsubstituted triple bonds and mono- and disubstituted alkene moieties afford bicyclo[3.3.0]octenones in high yields with complete diastereocontrol. These results are explained by assuming the association of the lone electron pair at sulfur to the Co-alkyne complexes.