Intramolecular [2 + 2]cycloadditions of dialkylketenes with alkenes. Regiochemistry of intramolecular [2+2]cycloadditions of ketenes with alkenes

Unsaturated dialkylketenes 7a, 7b and 7c undergo intramolecular [2 + 2]cycloadditions to give 8a (45%), 9b (23%) and 9c (45%). Intramolecular cycloadditions of dialkylketenes give higher yields than intramolecular cycloadditions of monoalkylketenes, even though dialkylketenes are less reactive than monoalkylketenes. An intramolecular competition experiment with ketene 17 establishes that trans-alkenes are approximately 33 times more reactive than cis-alkenes in intramolecular cycloadditions. Ketene 36 furnishes 22% of the expected bicyclo[3.2.0]heptanone 37 and 28% of bicyclo[3.1.1]heptanone 38.     

Studies on stereoselective [2+2] cycloadditions between N,N-dialkylhydrazones and ketenes

Staudinger-like cycloadditions between chiral, non-racemic N,N-dialkylhydrazones 1 and functionalized ketenes constitute an efficient methodology for the stereoselective construction of the beta-lactam ring. The potential for fine tuning of the dialkylamino auxiliary structure, the availability of a high-yielding deprotection method for the release of the free azetidinones, and the high thermal and chemical stability of hydrazones as N-dialkylamino imines are highlighted as the key elements for the success of the strategy. This last aspect is of particular importance concerning generality: even hydrazones from easily enolizable aldehydes or from formaldehyde reacted to afford the corresponding cycloadducts with high chemical and stereochemical yields. The syntheses of the beta-amino-alpha-hydroxyacids (2R,3S)-phenylisoserine (42) and (2R,3S)-norstatin (45) were accomplished as illustrative examples of the synthetic utility of this procedure. A model system for the cycloaddition of g series auxiliaries was studied by ab initio computational methods. The collected results support a two-step mechanism through zwitterionic intermediates, and explain the observed absolute and relative stereochemistry in terms of the preferred outward cycloaddition to the Re face of the hydrazone.     

Dual catalysis in enantioselective oxidopyrylium-based [5 + 2] cycloadditions

A new method for effecting catalytic enantioselective intramolecular [5 + 2] cycloadditions based on oxidopyrylium intermediates is reported. The dual catalyst system consists of a chiral primary aminothiourea and a second achiral thiourea. Experimental evidence points to a new type of cooperative catalysis with each species being necessary to generate a reactive pyrylium ion pair that undergoes subsequent cycloaddition with high enantioselectivity.     

Highly diastereo- and enantioselective NHC-catalyzed [3+2] annulation of enals and isatins

The chiral N-heterocyclic carbene bearing a proximal hydroxy group derived from L-pyroglutamic acid was found to be an efficient catalyst for the [3+2] annulation of enals and isatins to give the corresponding spirocyclic oxindolo-γ-butyrolactones in good yield with good diastereo- and enantioselectivities.     

Intermolecular gold-catalyzed diastereo- and enantioselective [2+2+3] cycloadditions of 1,6-enynes with nitrones

Going for gold: The title reaction has been developed and demonstrates a wide substrate scope with respect to the 1,6-enynes and nitrones (see scheme; DCE = 1,2-dichloroethane, Tf = trifluoromethanesulfonyl). The results for the enantioselective versions are also presented.     

Cooperative, highly enantioselective phosphinothiourea catalysis of imine-allene [3 + 2] cycloadditions

A new family of phosphinthiourea catalysts was developed for the highly enantioselective synthesis of 2-aryl-2,5-hydropyrroles via a [3 + 2] cycloaddition of an electron-deficient allene with aryl and heteroaryl diphenylphosphinoylimines. The presence of both H2O and Et3N as additives was found to be important for achieving optimal rates. Dual activation of both nucleophile and electrophile by the bifunctional catalyst is invoked to account for the observed high reactivity and enantioselectivity.     

Intramolecular ketenimine-ketenimine [2 + 2] and [4 + 2] cycloadditions

Bis(ketenimines), in which the two heterocumulenic functions are placed in close proximity on a carbon skeleton to allow their mutual interaction, show a rich and not easily predictable chemistry. Intramolecular [2 + 2] or [4 + 2] cycloadditions are, respectively, observed when both ketenimine functions are supported on either ortho-benzylic or 2,2'-biphenylenic scaffolds. In addition, nitrogen-to-carbon [1,3] and [1,5] shifts of arylmethyl groups in N-arylmethyl-C,C-diphenyl ketenimines are also disclosed.     

Highly enantioselective catalytic [6+3] cycloadditions of azomethine ylides

Under control: Highly functionalized chiral annulated piperidines with eight stereocenters are efficiently obtained by means of a highly enantioselective one-pot [6+3]/[4+2] sequence. This sequence included the first enantioselective [6+3] cycloaddition of azomethine ylides with fulvenes.     

The scope of catalytic enantioselective tandem carbonyl ylide formation-intramolecular [3 + 2] cycloadditions

Catalytic enantioselective tandem carbonyl ylide formation-intramolecular 1,3-dipolar cycloaddition reactions of 2-diazo-3,6-diketoesters show promising scope in terms of asymmetric induction as the tethered alkene/alkyne dipolarophile component is varied. Cycloadditions were found to occur in moderate to very good yields, with a difference in ee exhibited by the electronically different 2-diazo-3,6-diketoesters 1, 25 and 33, 34. Values for ee of up to 90% for alkene dipolarophiles and up to 86% for alkyne dipolarophiles were obtained.     

Ruthenium-catalyzed [2 + 2] cycloadditions of ynamides

Ruthenium-catalyzed [2 + 2] cycloadditions between norbornene and ynamides were investigated. The ynamide moiety was found to be compatible with the ruthenium-catalyzed cycloaddition conditions, giving the corresponding cyclobutene cycloadducts in moderate to good yields (up to 97%). [reaction: see text]     

Catalytic enantioselective [2 + 4] and [2 + 2] cycloaddition reactions with propiolamides

We report here the catalytic and highly enantioselective [2 + 4] and [2 + 2] cycloaddition reactions of electron-rich dienes or silyl enol ethers with electron-deficient propiolamide derivatives induced by copper(II).3-(2-naphthyl)-L-alanine amide complex.     

DFT study on [4+2] and [2+2] cycloadditions to [60] fullerene

The functionalisation of C₆₀ fullerene with 2,3-dimethylene-1,4-dioxane (I) and 2,5-dioxabicyclo [4.2.0]octa-1(8),6-diene (II) was investigated by the use of density functional theory calculations in terms of its energetic, structural, field emission, and electronic properties. The functionalisation of C₆₀ with I was previously reported experimentally. The I and II molecules are preferentially attached to a C—C bond shared and located between two hexagons of C₆₀ via [4+2] and [2+2] cycloadditions bearing reaction energies of ?15.9 kcal mol^?1 and ?72.4 kcal mol^?1, respectively. The HOMO-LUMO energy gap and work function of C₆₀ are significantly reduced following completion of the reactions. The field electron emission current of the C₆₀ surface will increase after functionalisation of either the I or II molecule.     

Rhodium catalysed [2+2+2] cycloadditions of acetylenes

Wilkinson's catalyst RhCl(PPh₃)₃ is an effective catalyst (0.5 – 2 mole %) for the rapid intermolecular trimerisation of 1,6-heptadiynes with monoacetylenes under mild conditions.     

Frontier-orbital analyses of ketene [2+2] cycloadditions

Twelve kinds of ketene [2+2] cycloadditions have been investigated by ab initio calculations. They are composed of four ketenes (Y–HC=C=O, Y=H, NH₂, Cl, and CN) and three isoelectronic ketenophiles (ethylene, methylenimine, and formaldehyde). All the transition state geometries obtained here are not different significantly, but the extent of formation of two covalent bonds differs appreciably. The difference is attributable to the degree of the charge transfer interactions. One is the interaction from the π orbital and/or the lone pair orbital of a ketenophile to the LUMO of a ketene (dominant charge transfer, CT1). The other is that from the HOMO of the ketene to the π* orbital of the ketenophile (second dominant charge transfer, ct1). CT1 contributes to the formation of only one covalent bond, and ct1 does to the formation of the other. This independent function is characteristic of ketene [2+2] cycloadditions. They are not concerned with the orbital phase. We also have examined Fukui's postulate that the deformation of particular frontier orbitals causes the reaction progress. The role has been verified both by configuration analyses along the intrinsic reaction coordinate of the ketene-ethylene reaction and by the examination of distortions of frontier-orbital shapes along the low-frequency vibrational modes. Received: 25 June 1998 / Accepted: 28 August 1998 / Published online: 11 November 1998