Cope-like reaction

We have also recently shown that Bergman (Scheme 8.7) and related reactions (not shown) [84, 85] of polyunsaturated hydrocarbons, with a 1,3,5-hexatriene skeleton form a branch inside a larger Cope reaction family characterized by a common 1,5-hexadiene structural unit. The examination of this whole family of reactions allowed us to derive a very simple rule for involvement of transient biradicals in Cope-like reactions of hydrocarbons A non-concerted reaction takes place when biradical intermediates are stabilized either by aUyl or aromatic resonance [84, 85]. 

Enol formation provides the necessary 1,5-diene for the Cope-like rearrangement. If one provides an enolate anion, the ionic nature of the reaction provides the expected acceleration of rate. 

Dienone-phenol rearrangements are mechanistically diverse. They may involve 1,2-shifts of the Wag-ner-Meerwein type, or of the benzil-benzilic acid kind 1,3-shifts by a Claisen-Cope mechanism 1,5-sigmatropic shifts Favorskii-like reactions and other types. They may also be induced photochemically. A number of reviews are available, which discuss mechanistic aspects in detail. In this chapter emphasis is put on preparative aspects of these reactions and the examples are organized on a structural basis, stressing the new bond(s) formed. 

A radical-cation Cope rearrangement of 2,5-diphenylhexa-l,5-dienes under electron ionization conditions (by mass spectrometry at 70 eV) has been described to occur in the gas phase. The reaction directionality differs from that in a thermal transformation. The rearrangement of hexamethyl-Dewai-benzene 410 into hexamethylbenzene (equation 156) as well as the closure of the bridged hexahydrodiene 411 into the so-called birdcage hydrocarbon 412 proceed during hemin-catalyzed epoxidation via a radical cation intermediate (equation 157)224. These processes are Cope-like rearrangement because two double bonds are separated by one CHt group in 410 and by three -hybridized C-atoms in 411. 

Other Reactions, The allyl Grignard reagent (601) cyclizes on heating by a Cope-like transition state. The product after hydrolysis is predominantly the c/j-cyclopentyl-olefin (602), and a m-cyclopentane (603) is also obtained in the ene rearrangement of the corresponding diene. A non-cyclic mechanism is known to operate in intermolecular addition where intramolecular electrophilic assistance is available in the olefin, e.g, (604). ... 

We have already proposed such a plausible biogenetic pathway for three subtypes of vibsane-type diterpenes as vibsanin B (1) could be transformed into vibsanin C (2) by a Cope-type reaction, based on the results of thermal reactions of 1 [13,19]. Additional isolation of these furanovibsanins compel us to elaborate their biosynthetic process after 2 is produced. Thus, our proposed biosynthetic sequences leading to the furanovibsanins from 2 are outlined in Schemes 6 and 7. Biogenetic conversion of compounds 53-56 and 60 from vibsanin C (2) can be rationalized by a cationic process like (a) in Scheme 6 followed by an acetal formation between C-4 and C-7 ketones and intramolecular addition of oxygen nucleophiles. This is based on the fact that this type of tricyclic formation can be readily realized by... 

In further studies of vinyl-substituted diazoesters, Davies has made some remarkable observations pertaining to their reaction chemistry with dienes (Scheme 15.22) [99]. Interestingly, when 187 and cyclohexadiene 188 were allowed to react in the presence of Rh(I) catalyst 78, product 189 was obtained in 99% ee. Carefiil investigations of this transformation ruled out 189 being formed by a sequence involving C-H insertion followed by Cope rearrangement. Davies speculated that its formation proceeded through an intercepted C-H insertion process or an ene-like reaction of... 

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. 

Like [2 + 2] cycloadditions (p. 1082), Cope rearrangements of simple 1,5-dienes can be catalyzed by certain transition metal compounds. For example, the addition of PdCl2(PhCN)2 causes the reaction to take place at room temperature,This can be quite useful synthetically, because of the high temperatures required in the uncatalyzed process. 

It has also been reported" " that rearrangements of both a- and y-propylallyl triflinates on heating in acetonitrile yield the same sulfone y-propylallyl triflone. Although the possibility of an ion-pair mechanism may be responsible for the lack of allylic rearrangement in one case as a result of the better leaving group ability of the triflinate anion as compared with the arenesulfmate anion, it is just as likely a consequence of the unbuffered conditions in which these reactions were performed. In this respect this is reminiscent of the results observed by Cope and coworkers" mentioned above which were also performed under nonbuffered conditions, and which could be simply corrected by the addition of 2,6-lutidine . 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

On the contrary, a-lithiated epoxides have found wide application in syntheses . The existence of this type of intermediate as well as its carbenoid character became obvious from a transannular reaction of cyclooctene oxide 89 observed by Cope and coworkers. Thus, deuterium-labeling studies revealed that the lithiated epoxide 90 is formed upon treatment of the oxirane 89 with bases like lithium diethylamide. Then, a transannular C—H insertion occurs and the bicyclic carbinol 92 forms after protonation (equation 51). This result can be interpreted as a C—H insertion reaction of the lithium carbenoid 90 itself. On the other hand, this transformation could proceed via the a-alkoxy carbene 91. In both cases, the release of strain due to the opening of the oxirane ring is a significant driving force of the reaction. 

Oxidation of organonitrogen compounds is an important process from both industrial and synthetic viewpoints . N-oxides are obtained by oxidation of tertiary amines (equation 52), which in some cases may undergo further reactions like Cope elimination and Meisenheimer rearrangement . The oxygenation products of secondary amines are generally hydroxylamines, nitroxides and nitrones (equation 53), while oxidation of primary amines usually afforded oxime, nitro, nitroso derivatives and azo and azoxy compounds through coupling, as shown in Scheme 17. Product composition depends on the oxidant, catalyst and reaction conditions employed. 

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