Cyclobutane intermediate

Bradshaw et al. 67) were the first to propose a reaction pathway that is compatible with a transalkylidenation scheme. They suggested that the reaction proceeds via a quasi-cyclobutane intermediate. Applied to linear alkenes, this is pictured as follows ... 

Many authors assume that the reaction indeed proceeds in such a way, with the specification that the quasi-cyclobutane intermediate corresponds with a complex of cyclobutane with C4-symmetry (3, 13, 2%, 46, 49, 68-72). The role of the catalyst is described by these authors in terms of the forbidden-to-allowed concept of Mango and Schachtschneider 73, 74), in which the assumption is made that the formation of the cyclobutane complex is the result of a concerted fusion of two alkenes. In the following this will be considered in more detail. 

As an alternative to the cyclobutane mechanism there have also been proposed mechanisms involving carbene complexes2 which cannot be considered as a more detailed description of the quasi-cyclobutane intermediate, as in the case of the tetramethylene complex. H6risson and Chauvin 88) proposed the following scheme for the transalkylidenation step ... 

In the crystal of 1,4-dicinnamoylbenzene (1,4-DCB) (see Fig. 12), the distances between the intermolecular photoadductive carbons are 3.973 and 4.086 A for one cyclobutane ring, and 3.903 and 3.955 A for the other. The two topochemical pathways may occur competitively in a single crystal of 1,4-DCB at the initial stage of reaction. Then, both intramolecular photodimerization and intermolecular photopolymerization of the diolefinic mono-cyclobutane intermediate occur competitively to give tricyclic dimer 21,22,23,24-tetraphenyl-l,4,ll,14-tetraoxo-2(13),12(13-diethanol, [4.4] para-cyclophane or oligomers (Hasegawa et al., (1985). On photoirridation at room temperature the 1,4-DCB crystal gives >90% of the tricylic... 

The product of simple addition across the double bond is only weakly acidic whereas the final product has a hydrogen activated by two carbethoxy groups and is removed from the equilibrium by conversion to the enolate salt. The stability of the final salt serves to drag the reaction over the barrier that the cyclobutane intermediate must represent. 

When alkenes are allowed to react with certain catalysts (mostly tungsten and molybdenum complexes), they are converted to other alkenes in a reaction in which the substituents on the alkenes formally interchange. This interconversion is called metathesis 126>. For some time its mechanism was believed to involve a cyclobutane intermediate (Eq. (16)). Although this has since been proven wrong and found that the catalytic metathesis rather proceeds via metal carbene complexes and metallo-cyclobutanes as discrete intermediates, reactions of olefins forming cyclobutanes,... 

Reactions of Cjq with metal carbene complexes also yield the [6,6] methano-fullerenes [392]. These adducts are probably not formed via a carbene addition, but via a formal [2-1-2] cycloaddition under formation of a metalla cyclobutane intermediate. The Fischer carbene complex [mefhyl(methoxymethylene)]pentacarbonyl chromium can be utilized to prepare l,2-mefhyl(methoxymethano)-fullerene in 20% yield [392]. A tungsten carbene complex was primarily used to initiate the formation of a polyacetylene polymer, but it was discovered that addition of to the complex-polymer-mixture improves the polymerization and dramatically increases the catalytic activity of the carbene complex [393]. can be integrated into the polymer via carbene addition. 

An intermolecular [2+2] photocycloaddition of 2,2-dimethyl-l,3-dioxin-4-one and A -methyldihydropyrrole was the key step in the synthesis of kainic acid analogs. The cyclobutane intermediate was hydrolyzed with sodium methoxide to give ketoester 181 in good yield (Scheme 40) <2002SL167, 2003T3307>. 

In order to interpret the remarkably high activity of platinum to promote isomerization of neopentane to isopentane, the direct formation and involvement of metalla-cyclobutane intermediate 18 was suggested.152,158 This a,y diadsorbed species bonded to a single platinum atom is in accordance with the existence of platinum complexes and the ability of platinum to catalyze a-y exchange.156,159... 

The six-membered ring 85 is obtained from the allylamine 84 [31]. The sulfur-containing ring 87 was obtained from 86 using the Mo catalyst. The Ru catalyst is not active for this reaction [32]. The (S, f )-chromene derivative 89 was obtained in 97% yield by the Mo-catalysed intramolecular metathesis of (S,f )-cycloheptenyl styrenyl ether 88 under an atmosphere of ethylene. In the absence of ethylene, 89 and its dimer were obtained. The enantioselective total synthesis of (.S, / ,/ , / )-ncbivoIoI (90) has been carried out from 89 [33]. No cyclization of the cyclopentene 91 was observed, because the highly strained cyclobutane intermediate 92 is difficult to form. 

Pt(II) to the alkyne of the substrate likely triggers all these events. The cycloisomerization might undergo a metallacyclic intermediate that proceeds to eliminate /3-H. The formation of cyclopropanes is presumably succeeded via alkenyl platinum carbene followed by platina(IV)cyclobutane intermediates. The extension using formal metathesis of the enynes includes two transformations, the formation of 1,3-diene moieties and the stereoselective tetrasubstituted aUcene derivatives via O C allyl shift, both leading to diverse structural motifs and serving as the key step in the total synthesis of bioactive targets (Scheme 83). 

Photocycloaddition of ethoxyethene to the enone (81) at 254 nm in methanol affords the adduct (82). Addition of the same alkene to the enone (83) also proceeds via a cyclobutane intermediate but this is unstable and ring opens to afford the cyclo-octane derivative (84). A study of the addition of the optically active alkene (85) to the enone (86) affords four cyclobutane adducts two from head-to-head addition and two from head-to-tail addition. These cycloadditions load to a double induction giving either increased or decreased diastereoselectivity.The intermolecular cycloaddition of ethylene to the enone (87) yields the two adducts (88) and (89). The photoadducts are apparently susceptible to secondary irradiation and the maximum yields of the adducts was obtained at 50% consumption of the starting material (87). Under these conditions (88) and (89) were obtained in 71 and 23% respectively. The isomer (88) was taken on through several steps to afford ultimately racemic starpuric acid a... 

The understanding of the reaction mechanism is directly related to the role of the catalyst, i.e., the transition metal. It is universally accepted that olefin metathesis proceeds via the so-called metal carbene chain mechanism, first proposed by Herisson and Chauvin in 1971 [25]. The propagation reaction involves a transition metal carbene as the active species with a vacant coordination site at the transition metal. The olefin coordinates at this vacant site and subsequently a metalla-cyclobutane intermediate is formed. The metallacycle is unstable and cleaves in the opposite fashion to afford a new metal carbene complex and a new olefin. If this process is repeated often enough, eventually an equilibrium mixture of alkenes will be obtained. 

Both cis- and trans-2-butene give cyclopropane with retention of the alkene geometry. Propene, styrene, 2-methyl-2-butene lead to the predominant formation of the thermodynamically less stable cis-cyclopropane (see Table 4). However, this cannot be explained, as suggested earlier, by a preferred stereochemistry of a hypothetical metalla-cyclobutane intermediate. 

A few model reactions known from the literature also support the idea of an oxametalla-cyclobutane intermediate such as the formation of the irida(III)oxetane 10 modeling the metal-mediated transfer of oxygen to a coordinated olefin (step B). This reaction is explained by autoxidation of the iridium(I)-cyclo-octadiene complex 9 via the plausible dinuclear oxoiridium(III) intermediate. [15]... 

The disproportionation of propylene on supported tungsten oxide catalysts is thought to proceed via a cyclobutane intermediate as follows. 

In this view the decomposition of the cyclobutane intermediate would be the rate-determining step. Alternative views hold that the first step above should be broken into two steps, adsorption of and surface reaction of 2C (ads) to form the intermediate, or that the formation of intermediate... 

A number of miscellaneous methods have been described for the preparation of nine-membered sulfur-containing compounds. The enamine (394) reacted with the thiirene dioxide (395) to give the nine-membered product (396), presumably via a cyclobutane intermediate (Equation (39)) <74JOC3805>. 

Similarly, a tetrameric platina(IV)-cyclobutane intermediate 37 was postulated in the ring homologation reaction of tetracyclo[3.3.1.0 . 0 ]nonane (38), which on treatment with Zeise s dimer (C2H4PtCl2)2 led cleanly to the alkene 39 (equation 16). The mechanism of this rearrangement was established by studies with deuterium and labelling experiments. 

This interesting reaction proceeds through initial intramolecular [2-I-2]-cycloaddition to afford tricyclic cyclobutane intermediate 40. 

The cyclobutane intermediate is not an irreversible sink for the catalyst, but remains reversibly linked to the catalytic cycle. In this mechanistic scenario, the enantioselectivity of the reaction does not depend on the difference of the activation energies for the electrophilic attack on the two diastereotopic faces of the enamine intermediate and is controlled, according to the Curtin—Hammett principle, by the relative stability and reactivity of the diastereomeric intermediates (cyclobutane and enamine of the Michael adduct) downstream in the catalytic cycle [58, 60]. A very recent detailed mechanistic study of another reaction catalyzed by diarylproUnol sdyl ethers, the a-chlorination of aldehydes by iV-chlorosuccinimide, also suggests that the stereochemical outcome of this process is not determined by the transition state of the electrophilic attack to the enamine, but instead is correlated with the relative stability and reactivity of the diastereomeric 1,2-addition products from the resulting iminium intermediate [60]. 

A detailed kinetic study of the conjugate addition of propanal to )8-nitrostyrene, as catalysed by diphenylproUnol TMS ether, indicates that the formation of the iminium intermediate is rate determining and that this step is catalysed by both the acid additives and the final product. A cyclobutane intermediate (72) has been characterized in three... 

A re-examination of proline-catalysed enantioselective Michael addition of aldehydes (R CH2CH0) with fran -nitroalkenes (R CH=CHN02) has identified a cyclobutane intermediate (109) derived from the reactants and catalyst. In situ NMR was used to discover the presence of (109) and to And that it represents a parasitic or resting state, arising from the iminium nitronate zwitterionic intermediate, siphoning it out of the productive catalytic cycle. Detailed kinetic studies also shed light on the role of acid catalysts and stability of the cyclobutanes (109) towards water and 0 aldehyde. For a similar possibly parasitic intermediate (72), see section titled The 0 Henry (Nitroaldol) Reaction . 

The classic de Mayo reaction involves the [2 + 2] photocycloaddition of an alkene to the hydrogen-bonded enol tautomer of a P-dicarbonyl compound as exemplified by the formation of 1,5-diketone 9 from pentane-2,4-dione and cyclohexene (vide supra). In addition to alkenes, allenes are also used as the olefinic component. For example, irradiation of a mixture of dimedone and allene results in the formation of 3,3-dimethyl-7-methylenecycloocta-l,5-dione 12 via the cyclobutane intermediate 11, together with the corresponding head-to-tail product 13, which spontaneously dimerizes to the hetero Diels-Alder adduct 14. Diketone 12 is a versatile building block for the preparation of substituted cyclooctadienones and 8-valerolactones. 

The intramolecular photoaddition of vinylogous esters with allenes has also been explored. Thus photocycloadition of 82 leads to the formation of the bicyclic furan 84 in moderate yield. This furan derivative is prepared from the cyclobutane intermediate 83, which results from the parallel addition to the terminal olefin of the allene. However, this approach does not work for the acyclic vinylogous ester 85. Irradiation of this ester provides none of the expected furan product 87 and results only in isomerization of the vinylogous ester. 

The photocycloaddition-retro-Mannich-Mannich methodology is featured in a concise synthesis of mesembrine. Irradiation of vinylogous amide 114 effects photocycloaddition-re/ro-Maimich sequence to give product 116 via the cyclobutane intermediate 115. Methylation with trimethyloxonium tetrafluoroborate followed by treatment with DMAP produces mesembrine in 84% yield. Other applications include construction of the bicyclic core of peduncularine and synthetic approaches to hetisine alkaloids and 8-substituted 6-azabicyclo[3.2.1]octan-3-ones. ... 

Irradiation of 231 gives, after the re ra-Mannich fragmentation of the photoadduct 232, a 91% yield of 233. The single stereogenic center in the photosubstrate leads to complete stereochemical control in the formation of the cyclobutane intermediate 232, which contains two new strereogenic centers. Treatment of 233 with lithium diisopropylamide, followed by an excess of ier butyldimethylsilyl triflate and reaction of the crude product with tetrabutylammonium fluoride, results in the formation of the desired tetracyclic product 234 in 51% yield. This compound is converted to tetracyclic ketone 235, which is an advanced intermediate in Buchi s synthesis of vindorosine. 

Finally, despite the plethora of reports providing evidence for the one carbene exchange mechanism, in certain circumstances cyclobutanes can be converted quantitatively into diolefins and, of greater importance, two non-conjugated olefinic groups (31) can be converted into a cyclobutane (32) almost quantitatively by the methathesis catalyst PhWCls-AlCla. This suggests that the carbene mechanism is not a unique pathway for olefin disproportionation and that in some circumstances cyclobutane intermediates may be formed. 

This model is modified by Pino [300,301], Corradini [302], Kissin [303], Keii [304], Terano [305], Cecchin [306] to other titanium complexes. Bimetallic models between the titanium compound and the cocatalyst were discussed by Sinn and Patat [137], Pino [301], and Zakharov [307]. Others suggest that the growing polymer chain is bound to the transition metal through a double bond (carbene complex) and that the insertion reaction occurs through formation of a metal-cyclobutane intermediate [308,309]. 

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