Diene compounds Cope rearrangement

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. 

As we have indicated with our arrows, the mechanism of the uncatalyzed Cope rearrangement is a simple six-centered pericyclic process. Since the mechanism is so simple, it has been possible to study some rather subtle points, among them the question of whether the six-membered transition state is in the boat or the chair form. ° For the case of 3,4-dimethyl-l,5-hexadiene it was demonstrated conclusively that the transition state is in the chair form. This was shown by the stereospecific nature of the reaction The meso isomer gave the cis-trans product, while the ( ) compound gave the trans-trans diene. If the transition state is in the chair form (e.g., taking the meso isomer), one methyl must be axial and the other equatorial and the product must be the cis-trans alkene ... 

The Cope and oxy-Cope rearrangement are very useful in organic synthesis, particularly when the 1,5-diene system is incorporated in a ring, then intringuing cyclic compounds may result. Also, the Cope and oxy-Cope rearrangements are greatly facilitated for a cw-1,2-divinylcyclobutane (Eq. 15)), resulting in the formation... 

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). 

The kinetically controlled Cope rearrangement of 2,5-bis(4-methoxyphen-yl)hexa-l,5-dienes induced by photosensitized electron transfer to DCA was examined by Miyashi and co-workers [101-103]. Remarkable in this context was the temperature-dependent change of the photostationary ratio of this rearrangement, yielding the thermodynamically less stable compound at — 80°C in 96%. A radical cation-cyclization diradical cleavage mechanism (RCCY-DRCL) is... 

When there is a hydroxyl substituent at C-3 of the diene system, the Cope rearrangement product is an enol, which is subsequently converted to the corresponding carbonyl compound. This is called the oxy-Cope rearrangement.143 The formation of the carbonyl compound provides a net driving force for the reaction.144... 

When the diene is acyclic, [4+4] cycloaddition remains the primary reaction pathway even when the result is a highly reactive and unstable trans-alkene product, e.g., 150 and 151 (Sch. 35). With 1,3-butadiene, these intermediates are intercepted by an additional equivalent of the diene, to give the 2 1 adducts 152 and 153. When a diene is used that cannot achieve an s-cis conformation such as 154, Diels-Alder reaction with [4+4] adducts 155 and 156 is impossible and these compounds relieve strain via Cope rearrangement to give cyclobutanes 157 and 158, respectively [98]. An intramolecular version of this reaction has been reported [99]. 

In these cases a modification of the rearrangement, the so-called oxy-Cope rearrangement, is preferred. Thermolysis of a 3-hydroxy-l,5-diene results in the expected 1,5-diene system, but one of the olefinic bonds formed in this process is an enol, which can tautomerize to the corresponding ketone. Thus, a reverse Cope rearrangement cannot take place. Examples are shown in Scheme V/2 [13]. This reaction sequence has been investigated using the thermal behavior of two 1,2-divinylcyclohexanols as model compounds. The trans-iso-... 

The unhomogeneous composition of the products generated by the photochemical reaction is due to another mechanism. While the thermal isomerization of 1,5-dienes proceeds via a cyclic transition state in a synchronous sense, the photochemically induced transformation causes a reorientation of the allyl radicals generated from the educts. Warming up the reaction mixture to 100°C activates a complete transfer from 4c to 5c) of all isomers. This step may be explained by a radical CC bond split of the 1,2-diphenylethylene unit. Since the isomerization of the diastereomeric compound 4c to 5c is activated at much lower temperatures than for the Cope rearrangement (from 3c to 4c), it is clear that the thermal transfer exclusively forms the twofold changed product. 

The Claiscn rearrangement of allyl vinyl ethers is usually an irreversible reaction due to the energetic benefit of forming aC-O double bond. However, in strained bicyclic systems the retro-Claisen rearrangement (3-oxa-Cope rearrangement) of y,<5-unsaturated aldehydes has been observed32. Sometimes equilibrium mixtures of vinyl ether and carbonyl compound were found. For example, the ratio of the valence tautomers, bicyclo[3.1.0]hex-2-ene-6-cWo-methanal to 2-oxabicyclo[3.2.l]octa-3,6-diene, is approximately 7 333. Nevertheless this reaction was used in the preparation of a key intermediate in a prostacyclin synthesis34. 

The reaction of cycloheptatriene with 2,S-dimethyl-3,4-diphenylcyclopentadienone is typical for this class of compounds, resulting in the formation of six distinct products. Equation (5) displays the major products of interest, which include a modest quantity of the exo [6 -i- 4] adduct (82). The mechanistic details of this process were gleaned from monitoring an equimolar mixture of the two reactants maintained at 120 C. This experiment revealed that both the [2 -I- 4] adduct (83) and the [6 + 4] adduct (82) were formed from the outset of the reaction. However, adduct (83) was subsequently converted quantitatively into the [4 -I- 2] cycloadduct (84) via a Cope rearrangement. This interconversion is reminiscent of a similar transformation in the tropone-diene series (see Section 5.2.2.1.1 and ref. 24). 

The cytotoxic sesquiterpenoid (-)-quadrone, isolated from the fungus Aspergillus terreus, possesses the constitution and absolute stereochemistry shown in (218). The tricyclic carbon skeleton of this interesting natural product is the same as that found in compound (198), which, as described above (Scheme 28), is readily prepared by thermolysis of the tricyclic diene (197). Thus, it appeared that the Cope rearrangement of a suitably substituted and functionalized derivative of (197) might serve effectively as a key intermediate in a total synthesis of ( )-quadione (218) that is, successful Cope rearrangement of a substrate, such as (219), would provide, stereoselectively, the tricyclic substance (220). Presumably, the intermediate (220) could then be converted into the keto aldehyde (221), which had already been transformed into ( )-quadrone (218). ... 

A successful formal total synthesis of ( )-quadrone (218) via a route in which a divinylcyclopropane rearrangement played a key role was achieved by employing the substrate (228 Scheme 32). This material is readily prepared from the ketone (227) and, in contrast to compounds (219) and (224), undergoes smooth Cope rearrangement to the tricyclic diene acetal (229), which is easily transformed into the keto acetal (230). A rather lengthy sequence of reactions effects conversion of (230) into the keto aldehyde (221), which, as mentioned previously, has served as an intermediate in a total synthesis of ( )-quadione (218)."... 

The key to identifying Cope and Claisen rearrangements is the 1,5-diene in the starting material or in the product. A y,5-unsaturated carbonyl compound (a 1,5-heterodiene) can be made by a Claisen rearrangement, and a 5,e-unsaturated carbonyl compound can be made by an oxy-Cope rearrangement. 

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