Diastereoselective cobalt-mediated [2 + 2 + 2] cycloadditions of substituted linear enediynes phosphine oxides: scope and limitations

Variously substituted linear enediynes phosphines oxides possessing the double bond at either the terminal or internal position and with the phosphine oxide appended onto the alkyne or the alkene terminus have been prepared. Their cobalt(I)-mediated cyclizations produce the eta(4)-complexed tricyclic compounds in high yields. The endo/exo selectivity depends on both the position of the phosphine oxide on the enediyne and the position of the double bond in the tether. With chiral phosphine oxides, a certain degree of induction was observed, and depending on the substituents on the phosphorus atom, the diastereoselectivity can reach 74%. Up to now, it is the highest level reported for such a cyclization in which a stereogenic center is created. Regarding all of our results, two reaction pathways involving an initial coordination of the cobalt moiety on the chelating site of the substituent have been suggested to explain the observed selectivities.     

Recent progress in cobalt-mediated [2 + 2 + 2] cycloaddition reactions

For many years, our research group has been interested in the new developments of cobalt-mediated cyclizations. In this article, our recent achievements in the field of inter- and intramolecular [2 + 2 + 2] cyclizations are compiled.     

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.     

Synthesis and topology of [2+2] calix[4]resorcarene-based chiral cavitand-salen macrocycles

Chiral diastereomeric cavitand-salen macrocycles have been synthesized by the high-dilution condensation of a tris-(quinoxaline-bridged)-diformyl-calix[4]resorcarene with (1R,2R)-diphenylethylenediamine. The reaction produced a couple of diastereoisomers, consisting of two cavitand cavities bis-bridged by two chiral diimino moieties, which differ in a convergent (C-shaped) or divergent (S-shaped) orientation of the two cavities.     

The formal total synthesis of (+/-)-strychnine via a cobalt-mediated [2 + 2 + 2]cycloaddition

A short, highly convergent total synthesis of racemic isostrychnine, and thus strychnine, has been completed. The route involves 14 steps in the longest linear sequence and is highlighted by a cobalt-mediated [2 + 2 + 2]cycloaddition of an alkynylindole nucleus to acetylene.     

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]     

Kinetic resolutions of azomethine imines via copper-catalyzed [3 + 2] cycloadditions

An effective method has been developed for the kinetic resolution of racemic azomethine imines via [3 + 2] cycloadditions with alkynes catalyzed by a chiral copper complex. Efficient kinetic resolution is observed for a variety of N1 and C5 substituents on the dipole, thereby furnishing a wide array of useful enantioenriched azomethine imines, which can readily be transformed into monocyclic and bicyclic pyrazolidinones.     

Synthesis of 2-iodoynamides and regioselective [2+2] cycloadditions with ketene

The first synthesis of 2-iodoynamides is described as well as the first [2+2] cycloadditions of ketene with iodo alkynes.     

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     

Silver-catalyzed [2 + 2] cycloadditions of siloxy alkynes

We have described the first [2 + 2] cycloadditions of siloxy alkynes with a range of unsaturated carbonyl compounds. The reactions are efficiently promoted by substoichiometric amount of silver trifluoromethanesulfonimide and display excellent regio- and diastereoselectivity combined with a broad substrate scope. Our studies have established unambiguously the stepwise mechanism of this process and provided evidence for a novel role of silver in the catalytic cycle of the reaction, which involves silver-based complexation and activation of siloxy alkyne toward the subsequent 1,4-addition.     

Synthesis of cyclobutylideneacetic esters via aluminum chloride promoted [2+2] cycloadditions of ethyl 2,3-butadienoate to olefins

In the presence of AlCl₃, ethyl 2,3-butadiemoate reacts with a variety of olefins, including simple unactivated cycloalkenes, to give cyclobutylideneacetic esters at room temperature. The cycloaddition is regioselective and stereoselective.     

NHC-catalyzed enantioselective [2 + 2] and [2 + 2 + 2] cycloadditions of ketenes with isothiocyanates

The enantioselective N-heterocyclic carbene-catalyzed formal [2 + 2] and [2 + 2 + 2] cycloaddition of ketenes and isothiocyanates were developed. Reaction with N-aryl isothiocyanates at room temperature favors the [2 + 2] cycloaddition, while reaction with N-benzoyl isothiocyanates at -40 °C favors the [2 + 2 + 2] cycloaddition.     

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.     

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.     

Mechanically facilitated retro [4+2] cycloadditions

Poly(methyl acrylate)s (PMAs) of varying molecular weights were grown from a [4+2] cycloaddition adduct of maleimide with furan containing two polymerization initiators. Subjecting the corresponding PMA (>30 kDa) chains to ultrasound at 0 °C resulted in a retro [4+2] cycloaddition reaction, as observed by gel permeation chromatography (GPC) and UV-vis spectroscopy, as well as labeling of the liberated maleimide and furan moieties with appropriate chromophores featuring complementary functional groups. Similar results were obtained by sonicating analogous polymers that were grown from a thermally robust [4+2] cycloaddition adduct of maleimide with anthracene. The generation of anthracenyl species from these latter adducts allowed for the rate of the corresponding mechanically activated retro [4+2] cycloaddition reaction to be measured. No reduction in the number average molecular weight (M(n)) or liberation of the maleimide, furan, or anthracene moieties was observed (i) for polymers containing the cycloaddition adducts with M(n) < 20 kDa, (ii) for high molecular weight PMAs (M(n) > 60 kDa) featuring terminal cycloaddition adducts, or (iii) when the cycloaddition adducts were not covalently linked to a high molecular weight PMA. Collectively, these results support the notion that the aforementioned retro [4+2] cycloaddition processes were derived from a vectorially opposed mechanical force applied to adducts embedded within the polymer chains.     

Ruthenium-catalyzed [2 + 2] cycloadditions of 2-substituted norbornenes

The studies of remote substituent effects in controlling regio- and stereoselectivities in chemical reactions provide important information in understanding long-range stereoelectronic effects. The effect of remote substituents on ruthenium-catalyzed [2 + 2] cycloadditions of 2-substituted norbornenes has been investigated. The cycloadditions occurred at room temperature in excellent yields, and regioselectivities of 1.2:1 to 7.5:1 were observed with various 2-substituted norbornenes.