Addition reactions cyclo

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

The chemistry of dehydrobenzene, the parent aryne, has become well established during the past almost twenty years 4>. It is essentially the chemistry of a short lived (half-life ca. 10-4 sec.), and highly electrophilic intermediate. It reacts with a large number of nucleophiles, and undergoes cyclo-addition reactions with a wide variety of compounds. A number of observations have led us, and others, to concentrate our efforts on the tetrahalogenobenzynes. It seemed reasonable to predict that the presence of four electron withdrawing substituents on the aryne (1) would result in a significant increase in the electrophilicity compared with that of benzyne. 

From the Contents J. Michl Physical Basis of Qualitative MO Arguments in Organic Photochemistry. K.-D. Gundermann Recent Advances in Research on the Chemiluminescence of Organic Compounds. W.C. Herndon Substituent Effects in Photochemical Cyclo-addition Reactions. W.-D. Stohrer, P. Jacobs, K.H. Kaiser, G. Wiech,... 

Scheme 2.6 An immobilized selenium species for cyclo-addition reactions.

Starting material which, upon oxidation with PSP, gave aldehydes. These were in turn condensed with primary hydroxylamines, promoted by polymer-bound acetate, to produce nitrones. The nitrones assembled using either method then underwent 1,3-dipolar cyclo-addition reactions with various alkenes to give the corresponding isoxazolidines (Scheme 2.46 and 2.47). 

R. Gompper, Angew. Chem., Int. Ed. Engl. 8, 312 (1969) Cyclo-addition Reactions (R. Gompper, cd.). Butterworths, London, 1972 C. K. Bradsher, Advan. 

Tetrahaptocyclohexatriene- and cyclooctatetraene-metal-tricarbonyl complexes undergo some unusual cyclo-addition reactions with tetracy-anoethylene in which the dienophile undergoes a 1,3 addition across the coordinated ligand and causes a rearrangement of the metal-carbon bonds, for example (99),... 

It appears likely that transient metallacyclobutanes are involved in a variety of organic reactions which are catalyzed by transition metal complexes. Thus, cycloadditions of activated alkenes to strained hydrocarbons such as quadricyclane and bicyclo[2.1.0]pentane are catalyzed by complexes such as Ni(CH2=CHCN)2 and probably involve initial formation of a nickelacyclobutane (Scheme 2) (79MI12200). The nature of the organometallic intermediates in related metal-catalyzed rearrangements (72JA7757) and retro-cyclo-addition reactions (76JA6057) of cyclopropanoid hydrocarbons, e.g. bicyclo[n.l.O]alkanes, has been discussed. 

In contrast to V-heteroaldehyde and -ketone complexes, r -heteroalde-hyde complexes are less prone to cyclo addition reactions. The reactivity of these complexes is characterized by the insertion of C N, C=0, and C=N bonds into the M-C(heteroaldehyde) bond as has been demonstrated with the examples of zirconium and titanium complexes. 

Interest has been generated in the high-pressure method since it was demonstrated that high pressure is not only useful in effecting cyclo addition reactions, but also several kinds of ionic reactions [9-16]. The aim of the present article is to review recent examples of the use of high pressure for the synthesis of hetero cycles related to biologically interesting molecules, and to predict some further possibilities. The present review covers either representative or most recent examples. 

Numerous Amaryllidaceae alkaloids include phenanthridine skeletons, one of whose constructive methods constitutes an IEDA strategy. In some cases, the functionality on the dienophile influences the stereochemistry of cyclo addition reactions under high-pressure conditions. For example, the reactions of ( )-buta-l,3-dienyl acetate (6) and the quinolin-2(lH)-ones 7 gave rise to different configurations in the products 8 and 9, depending on the functional groups at the 4-position of 7 (Scheme 3). These results reflect... 

Alkyl-5-imino-3-methyl-A2-l,2,4-thiadiazolines react exothermally at 0°C with dibenzoyl or dimethoxy carbonylacetylenes in tetrahydrofuran to give the 2-aIkylaminothiazoles in high yields (1564). The cyclo addition reaction of 2-pyridyl isothiocyanates with 1-azirines results in the formation of 2-pyridylaminothiazoles (1565). 

Nitrogen-based heterocycles can also be prepared through Ni/NHC-catalyzed cyclo addition reactions. For example, Ni/SIPr catalyzed the cycloaddition of diynes with isocyanates under the mildest conditions to date [26]. In particular, excellent yields of pyridones are obtained from diynes and isocyanates at room temperature using only 3 mol % catalyst. As shown in Eq. 8, a variety of diynes were subjected to these optimized conditions. Both aryl and alkyl isocyanates were readily converted to the respective 2-pyridone. Sterically hindered substrates appeared to have very little effect on the reaction, as excellent yields of product were obtained with bulky isocyanates and bulky diynes. 

L. L. Muller and J. Hamer, 1,2-Cyclo-addition Reactions. Wiley (Interscience), New York, 1967. 

Greene, A.E., and Charbonier, F. 1985. Asymmetric induction in the cyclo-addition reaction of dichloroketene with chiral enol ethers. Aversatile approach to optically-active cyclopentenone derivatives. Tetrahedron Lett 16, 5525-5528. 

Example 7.7. Cyclo-addition reactions and the 4n + 2 rule. The predictive power of the Woodward-Hoffmann principle becomes apparent, for example, with the application to cyclo-addition reactions [32,35,36]. Consider first the dimerization of ethene to cyclobutane ... 

Examples include pyrolysis of an alkylbenzene homogeneous aldehyde hydrogenation olefin hydroformylation to alcohol with paraffin by-product formation, aldehyde condensation to heavy ends, and olefin isomerization cyclo-addition reactions and hydrogen-halide reactions. 

Complex 6 reacted with cyclopentadiene at ambient temperature ( ) in toluene in a J4+2]-cyclo-addition reaction to give phospha-norbomene complex 11 ( P NMR -69.1 ppm, 7(P,W) = 204.5 Hz), which reacted during the column chromatography to fiimish the / -H-substituted phospha-norbomene complex 12. Although complex 12 was fully characterized by NMR and MS spectroscopy, the confirmation was only tentatively assigned (Scheme S). 

The following rule can be derived for concerted cyclo-addition reactions. They can be described as 2+2+2 +.processes. Then we... 

Orbital symmetry relationships can be useful in the study of secondary conformational effects in concerted cyclo-addition reactions 6>. One example is the Diels-Alder addition of butadiene to itself. This n4s + 2a reaction may take place through an endo route (a) or an exo route (b), differing mainly by the proximity of a p and a (3 orbital in the endo approach. The secondary interaction among occupied orbitals in the two reactions will be negligible and the significant interaction will come from symmetry-allowed mixing of occupied orbitals in one reactant with unoccupied orbitals of the other. It is easily seen that mixing of both... 

An approach very closely related to that of Woodward and Hoffmann is the so-called Hiickel-Mobius approach 35> based on the rule An +2 electron systems prefer Hiickel geometries and An electron systems prefer Mobius geometries 36>. When no symmetry exists and there is no cyclic orbital array the allowedness or forbiddenness of a reaction can be determined by following the form of the MO s during the reaction 37>. A detailed quantum mechanical study of the stereochemistry of thermal and photo cyclo-addition reactions has been reported38), and a quantum mechanical discussion of the applicability of the Woodward-Hoffmann rules can be found in a paper by George and Ross 39>. 

Ring decomposition and the reverse cyclo-addition reactions... 

These kinetic parameters take into account the formation of a five-membered ring intermediate, the H-abstraction reaction of two H-atoms of allyl type and the formation of the resonantly stabilized l-hexen-3-yl radical. These facts explain why the reverse isomerization reaction requires greater activation energy. As clearly shown in Fig. 6, there is a new class of important reactions, i.e. ring decomposition (e.g., cyclo-hexyl to form hexenyl radical) and the reverse cyclo-addition reaction. The activation energies of ring decomposition to form primary radicals are 31,500 and 28,000 kcal/kmol respectively for the... 

An example for the determination of the kinetics of a solid-phase reaction via ATR-spectroscopy is shown in Figure 16.6. The cyclo-addition reaction leading to substituted isoxazolidines is initialized, and resin samples are taken out of the reaction mixture after certain time intervals [31]. ATR spectra were recorded to determine the relative intensities of the carbonyl vibration (v (C=0) = 1715 cm ).The spectra were normalized using the amide vibration (v(C(0)NFI2) = 1682 cm-1). 

It is not necessary to have a fully aromatic system for an intramolecular [4 + 2]-cyclo-addition reaction to take place. 3-(But-3-ynyIsulfanyI)-l,2,4-triazin-5(2//)-ones undergo intramolecular Diels Alder reactions, in competition with an intramolecular coplanar cycloamina-tion process, to provide and 1,3-thiazino[3,2-h]-l,2,4-triazin-3-ones 35 2,3-dihydrothieno-[2,3-6]pyridin-6(7//)-ones 36. The Diels-Alder reaction probably proceeds via the tautomeric... 

In principle, addition or elimination reactions involve significant bond formation or bond breakage in the transition state, such that an acceleration or deceleration is expected at elevated pressure, respectively. For instance, [2 -f 2] cyclo-addition reactions of the type shown in Scheme 1.1 were significantly accelerated by pressure, and there was almost no dependence on the polarity of the solvent [76]. 

Thermal (2 + 2)-cycloaddition reactions have never been reviewed so far, although occasionally a few reactions have been discussed in other review articles.20,21 The literature on this subject is summarized here in four subsections. First the mechanistic aspects of thermal (2 + 2)-cyclo-addition reactions are dealt with and subsequently a review is given of (2 + 2)-cycloadditions of heterocycles with olefins and compounds having other double bonds, with acetylenes, and with heterocumulenes. The reactions with acetylenes are discussed under two separate headings, covering (1) reactions with nonaromatic heterocycles and (2) reactions with heteroaromatics. The reactions included are exclusively inter-molecular (2 + 2)-cycloadditions. No examples are known of intramolecular thermal (2 + 2)-cycloadditions of two isolated -electron systems or of thermal electrocyclizations of conjugated 4/r-electron systems of heterocyclic compounds (Appendix). 

More recent views on the theory of (2 + 2)-cycloaddition, in particular with respect to the question whether the two novel o-bonds are formed via a concerted or a stepwise mechanism, have been presented by Epiotis.28 He predicts that, if in the reaction of two n -electron systems one of the reactants has an electron-donating and the other an electron-accepting character, the activation energy of the concerted non-allowed 1 2 + n2s]-cycloaddition will be lowered, so that such a reaction may occur in a concerted manner under relatively mild conditions. As this condition is satisfied in most of the reported thermal (2 + 2)-cyclo-addition reactions of heterocyclic compounds, care must be taken in drawing any conclusions as regards the reaction pathways followed. 

Furan has been found to form oxetanes with a variety of carbonyl compounds, e.g., ketones,202-205 aldehydes,206 and ethyl cyanofor-mate.207 In most reactions the (2 + 2)-cycloaddition occurred specifically to give a 2,7 dioxabicyclo[3.2.0]hept-3-ene (175) rather than the 2,6-isomer (176). Only the addition of ethyl cyanoformate yielded mixtures of 175 and 176 (R = OEt and R2 = CN), in a ratio of 2 l.207 Two subsequent (2 + 2)-cycloadditions of benzophenone and furans have been reported to give two isomeric products, 177 and 178.205 Substituted furans yielded similar oxetanes.203 Benzo[ >]furans, furo-coumarins, and furochromones also proved to undergo (2 + 2)-cyclo-addition reactions with carbonyl compounds such as ketones, aldehydes, and quinones. Invariably one type of oxetane was formed (179).,37,u3 ,44 200-202 208,20, In the case of 2-methoxycarbonylbenzo[6)-furan, evidence has been provided that the oxetane was produced by addition of the excited triplet state of the olefinic reactant to the ground state of the ketone.208... 

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