Cope rearrangement 2 + 2 cycloaddition

Ethyl 1 /T-azepine-l-carboxylate (1) and l,3-diphenyl-2/7-cyclopenta[/]phenanthren-2-one (26) (phencyclone) in refluxing benzene undergo a rapid peri- and regioselective cycloaddition to give the [4 + 2] 7t-e rfn-adduct 28 and not, as was first proposed, a [6 + 2] 7r-adduct.264 Subsequently, however, it was found that at room temperature a [2 + 4] 7r-cw/<>-adduct 27 is formed which readily undergoes a Cope rearrangement to the [4 + 2] endo,anti-adduct 28. 

At 75 C, 2-phenyl-l,3-oxazepine undergoes a [27r + 47t] cycloaddition to 2,5-dimethyl-3,4-diphenylcyclopentadienone to give 3, which at 120 C is transformed into the isomer 4 by a Cope rearrangement.16... 

Electronically rich 1,3-butadienes such as Danishefsky s diene react with chromium alkenylcarbene complexes affording seven-membered rings in a formal [4S+3C] cycloaddition process [73a, 95a]. It is important to remark on the role played by the metal in this reaction as the analogous tungsten carbene complexes lead to [4S+2C] cycloadducts (see Sect. 2.9.1.1). Formation of the seven-membered ring is explained by an initial cyclopropanation of the most electron-rich double bond of the diene followed by a Cope rearrangement of the formed divinylcyclopropane (Scheme 65). Amino-substituted 1,3-butadienes also react with chromium alkenylcarbene complexes to produce the corre-... 

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. 

Scheme 79 Snapper s total synthesis of asteriscanolide (116) by sequential intramolecular cyclobutadiene cycloaddition, ring-opening CM (ROCM), and Cope rearrangement [167]...

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. 

The Davies group has described several examples of a rhodium-catalyzed decomposition of a diazo-compound followed by a [2+1] cycloaddition to give divinyl cyclopropanes, which then can undergo a Cope rearrangement. Reaction of the pyrrol derivative 6/2-51 and the diazo compound 6/2-52 led to the tropane nucleus 6/2-54 via the cyclopropane derivative 6/2-53 (Scheme 6/2.11) [201]. Using (S)-lactate and (R)-pari lolaclorie as chiral auxiliaries at the diazo compound, a diastereoselectivity of around 90 10 could be achieved in both cases. 

Cyclopropanation of l,3-dienes. a,0-Unsaturated carbenes can undergo [4 + 2]cycloaddition with 1,3-dienes (12, 134), but they can also transfer the carbene ligand to an isolated double bond to form cyclopropanes. Exclusive cyclopropanation of a 1,3-diene is observed in the reaction of the a,(3-unsaturated chromium carbene 1 with the diene 2, which results in a frans-divinylcyclopropane (3) and a seven-membered silyl enol ether (4), which can be formed from 3 by a Cope rearrangement. However, the tungsten carbene corresponding to 1 undergoes exclusive [4 + 2]cycIoaddition with the diene 2. 

In the Lewis acid catalysed reactions of a,/J-unsaturated carbonyl compounds with dienes, sometimes the products of a [2 + 4]-cycloaddition, where the carbonyl compounds function as heterodienes, were isolated. It was proposed that the intermediate of the [2 + 4]-cycloaddition is formed first in this case, followed by a Cope rearrangement which leads to the normal Diels-Alder product (Scheme 7). 

In particular the synthetic approach to dihydrofurans (first equation in Figure 4.23) represents a useful alternative to other syntheses of these valuable intermediates, and has been used for the preparation of substituted pyrroles [1417], aflatoxin derivatives [1418], and other natural products [1419]. The reaction of vinylcarbene complexes with dienes can lead to the formation of cycloheptadienes by a formal [3 + 4] cycloaddition [1367] (Entries 9-12, Table 4.25). High asymmetric induction (up to 98% ee [1420]) can be attained using enantiomerically pure rhodium(II) carboxylates as catalysts. This observation suggests the reaction to proceed via divinylcyclopropanes, which undergo (concerted) Cope rearrangement to yield cycloheptadienes. 

One of the early examples demonstrating the efficiency of this chemistry was the [3+4] cycloaddition reaction of diazoglutaconate 42 with cyclopentadiene, in which the endo-isomer 43 is exclusively formed in 98% yield (Eq. 5) [73]. The intermediacy of a cis-divinylcyclopropane is consistent with the stereochemical outcome because it would rearrange to the endo-product. Indeed in the case of more highly functionalized vinyl-diazoacetates, the ds-divinylcyclopropane was isolable, in which elevated temperatures were required for the Cope rearrangement [73]. 

A direct entry into hydroazulenes has also been achieved through [3-I-4] cycloaddition chemistry, using the more elaborate cyclic vinyldiazoacetate 62 and acetoxybuta-dienes 63 and 64 (Scheme 14.6) [80]. The tandem process is facile with the trons-iso-mer of butadiene 64 leading to the [3-r4] cycloadduct 68 in 67% yield. Reaction with cis-acetoxybutadiene 63, however, forms the isolable cis-divinylcyclopropane 65 (80% yield), which required forcing conditions to initiate the Cope rearrangement to form 67 [80]. 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

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