Rearrangements 3,3 -Cope

SCHEME 9.1 Synthesis of N-protected glycosylamines employing the Chapman rearrangement. 

One of the new rearrangement reactions is a dyotropic rearrangement [6,7], It is an uncatalyzed process in which two o-bonds simultaneously migrate intramolecularly. This rearrangement is further classified as type 1 and type 2. Type 1 consists of reactions in which the two o-bonds interchange positions (e.g., rearrangement of nitrile oxide into isocyanate). In contrast, in type 2, the two o-bonds do not interchange positions. 

The Cope rearrangement constitutes a universal tool for the synthesis of new carbon skeletons. 

Synthesis of 3-amino-3-cyano-3-deoxy sugars via the Hofmann rearrange- 

2E corresponds to a free-energy difference of about 2 kcal/mol between transition states A and B. Based on the A-values of the monosubstituted cyclohexanes, it was understood that transition state A in which the phenyl subsitituent group occupies an equatorial position would be favored over B. 

A solution of the silylketene acetal 4 in dodecane was subjected to thermolysis at 200 C for 140 minutes. The Cope-Claisen rearrangement product 5 was then treated with KF in HMPA followed by esterification to afford the methyl ester 6. 

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Ring Expansion/Contraction via Sigrnatropic Rearrangements - Cope Rearrangement... 

The most intriguing hydrocarbon of this molecular formula is named buUvalene, which is found in the mixture of products of the reaction given above. G. SchrOder (1963, 1964, 1967) synthesized it by a thermal dimerization presumably via diradicais of cyciooctatetraene and the photolytical cleavage of a benzene molecule from this dimer. The carbon-carbon bonds of buUvalene fluctuate extremely fast by thermal Cope rearrangements. 101/3 = 1,209,6(X) different combinations of the carbon atoms are possible. 

The 5-oxohexanal 27 is prepared by the following three-step procedure (1) 1,2-addition of allylmagnesium bromide to an a, / -unsaturated aldehyde to give the 3-hydroxy-1,5-diene 25, (2) oxy-Cope rearrangement of 25 to give 26, and (3) palladium catalyzed oxidation to afford 27. The method was applied to the synthesis of A -2-octalone (28), which is difficult to prepare by the Robinson annulation[25]. 

The rearrangements of various allylic compounds catalyzed by both Pd(II) and Pd(0) are treated in this section[491]. Related reactions such as the Carroll rearrangement are treated in Section 2.10.1 and the Pd(II)-catalyzed Cope rearrangement is treated in Chapter 5, Section 3. 

The first report on the Pd(II)-promoted Cope rearrangement is the conversion of fw./ra/w-l,5-cyclodecadiene (44) into c/5-l,2-divinylcyclohexane-PdCl2 complex (45) with a stoichiometric amount of PdCl2(PhCN)2 at room temperature. The complex formation is the driving force of this unusual rearrangement [38,39]. A similar transformation of germacrane (l,5-dimethyl-8-isopropyli-dene-/rfflu,/ra j-l,5-cyclodecadiene) takes place[40j. 

The mechanism of the PdCh-catalyzed Cope rearrangement has been studied by use of the partially deuterated 1.5-diene 53[46], The coordination of Pd(II) activates the alkene, and cyclization (carbopalladation) takes place to... 

Oxy-Cope rearrangement of 56 to form the cyclic ketone 57 can be carried out at room temperature with catalysis by PdCl2(PhCN)2(47]. 

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

The synthesis of dehydro-hnalool (28) rehes on the basic chemicals acetone and acetjiene. Addition of a metal acetyUde to acetone yields methylbutynol (33). Semihydrogenation affords the alkene (34) which is reacted with /-propenylmethyl ether. A Cope rearrangement of the adduct yields methyUieptenone (35). Addition of a second mole of metal acetyUde to dehydro-linalool (28) is followed by a second Cope rearrangement to yield... 

TL2733,82TL2737). The reaction proceeds through an aza-Cope rearrangement of the initially formed iminium salt, followed by intramolecular cyclization. 

Many rearrangements forming C—C bonds have been applied to the preparation of heterocyclics. The Cope rearrangement is prominent, and an example is shown in Scheme 8. The staring material usually most accessible is an alkene, which is converted to the required cyclopropane at some stage before the rearrangement step. 

Cartion-cartxin bond formation via tandem Mannich condensation, cationic aza-Cope rearrangement of homoaHylarrunes, leading to pyrolidmes... 

Rearrangement ot 0-(2-pyrtdyi)oximes to 2-pyndones via a hetero-Cope rearrangement. 

Claisen or Cope rearrangement Ester cracking Conia ene reaction... 

The most important sigmatropic rearrangements from the synthetic point of view are the [3,3] processes involving carbon-carbon bonds. The thermal rearrangement of 1,5-dienes by [3,3] sigmatropy is called the Cope rearrangement. The reaction establishes equilibrium between the two 1,5-dienes and proceeds in the thermodynamically favored direction. The conversion of 24 to 25 provides an example ... 

The Cope rearrangement usually proceeds through a chairlike transition state. The stereochemical features of the reaction can usually be predicted and analyzed on the basis of a chair transition state that minimizes steric interactions between the substituents. Thus, compound 26 reacts primarily ttuough transition state 27a to give 28 as the major product. Minor product 29 is formed flirough the less sterically favorable transition state 27b. 

There is a second possible transition state for the Cope rearrangement in which the transition state adopts a boatlike geometry ... 

A dramatic diflference in reactivity is evident when cb-divinylcyclopropane is compared wifli vinylcyclopropane. ciy-Divinylcyclopropane can only be isolated at low temperature because it very rapidly imdeigoes Cope rearrangement to 1,4-cycloh ta-... 

The stereochemical features of the Claisen rearrangement are very similar to those described for the Cope rearrangement, and reliable stereochemical predictions can be made on the basis of the preference for a chairlike transition state. The major product has the -configuration at the newly formed double bond because of the preference for placing the larger substituent in the pseudoequatorial position in the transition state. ... 

Like the Cope rearrangement, the Claisen rearrangement is sensitive to substituents on the reacting system. Cyano groups promote the rearrangement by a factor of 10 at positions 2 and 4 and have smaller effects at the other positions, as shown below. Data are also available for methoxy groups at positions 2, 4, 5, and 6. ... 

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