Stereospecificity Cope rearrangement

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 mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

Moore RE, Pettus JA Jr (1971) Isolation and structure determination of dictyopterenes C and D from Dictyopteris. Stereospecificity in the cope rearrangement of dictyopterenes A and B. J Am Chem Soc 93 3087-3088... 

The Cope rearrangement is the conversion of a 1,5-hexadiene derivative to an isomeric 1,5-hexadiene by the [3,3] sigmatropic mechanism. The reaction is both stereospecific and stereoselective. It is stereospecific in that a Z or E configurational relationship at either double bond is maintained in the transition state and governs the stereochemical relationship at the newly formed single bond in the product.137 However, the relationship depends upon the conformation of the transition state. When a chair transition state is favored, the EyE- and Z,Z-dienes lead to anli-3,4-diastereomcrs whereas the E,Z and Z,/i-isomcrs give the 3,4-syn product. Transition-state conformation also... 

Dihydropyridines have also been starting points for stereospecific syntheses of hydro-phenanthridines and isoquinolines. Interest exists in these compounds because of the occurrence of this structural feature in alkaloids. For example, isoquinuclidine (263), derived from JV-alkoxycarbonyl-l,2-dihydropyridine, undergoes a Cope rearrangement to give the isoquinoline derivative (264) (80JA6157). Further chemical transformations of (264) provided a formal total synthesis of reserpine (Scheme 50). 

Similarly, the [3 + 4] annulation of the E- and Z-isomers of /1-heteroatom-substituted acryloylsilanes 156 with lithium enolates of ,/l-unsaturated methyl ketones 157 gave stereospecifically cis-5,6- and //r/w.v-5,6-disubstituted-3-cycloheptenones 160, respectively (equation 97). The stereospecificity in the annulation was explained by an anionic oxy-Cope rearrangement of the 1,2-divinylcyclopropanediol intermediate 159, which was generated through the Brook rearrangement of the initial 1,2-adduct 158219 - 223. 

The product is a mixture of diastereoisomers because of the chiral centre already in the molecule (ringed in green), but it is, of course, fully stereospecific for the two new black chiral centres in the four-membered ring. The next step adds vinylmagnesitim bromide to the ketone—again a mixture of diastereoisomers results. Now all the carbons in the I2-membered ring are present, and they are sorted out by the two steps that follow. The first is a Cope rearrangement a [3,3]-... 

These two anr/-reactions have been used for a stereospecific synthesis of dihydrone-petalactone (7) from norbomenone (3).5 Addition of propynylmagnesium bromide, followed by Lindlar reduction of the triple bond, acetylation, and reaction with 2, provides the allylsilane 4. Epoxidation of 4 and desilylation results in 5. Oxy-Cope rearrangement of 5 results in a single ketone (6) with the desired four chiral centers. The remaining steps to 7 involve conventional reactions. 

TCNE takes place (Scheme 57). Tomioka reported the (3 + 2) photocycloaddition between 1,1,2-triarylcyclopropanes and vinyl ethers in the presence of p-DCB [162]. Mizuno and Otsuji reported the (4 -l- 2) photocycloaddition between 1,2-diarylcyclopropanes and DCA [23]. The 1,4-radical cation produced as an intermediate of the Cope rearrangement of 1,5-dienes via photoinduced electron transfer can be trapped by molecular dioxygen, giving bicyclic dioxanes (Scheme 58) [163]. This photooxygenation takes place in a stereospecific manner. 

The readily available aldehyde (118) has served as a suitable precursor for a number of 6-endo-( al-kenyl)bicyclo[3.1,0]hex-2-enes. For example, treatment of (118) with PhsP —CHC02Me gives a mixture of die bicyclic diene esters (121)-(123) (Scheme 18). In view of the stereospecific nature of the Cope rearrangement process (vide supra), it is highly likely that (121) and (122) are derived by bond reorganization of the initially formed Wittig products (119) and (120), respectively. The ratio of (121) (122) is, therefore, a reflection of the (expected) fact that the Wittig reaction produces primarily the rrans-a,P-un-saturated ester (119). The diene ester (123) is, presumably, formed by partial isomerization of (121) and (or) (122). 

Vapor phase thermolysis of 2,5-hexadien-l-ols at 260°C affords cyclopropylmethyl ketones . The reaction has been proposed to proceed via homodienyl migration of hydrogen and is stereospecific (equation 118). l-(l-Alkynyl)-2-vinyloxiranes undergo successive Cope rearrangements at 300-350°C to give 2-(l-alkynyl)cyclopropane-carbaldehydes (equation 119) . Acid-catalyzed intramolecular acetalization followed by... 

McComsey, D. F., Maryanoff, B. E. 3-Aza-Cope Rearrangement of Quaternary N-Aiiyi Enammonium Saits. Stereospecific 1,3 Aiiyi Migration from Nitrogen to Carbon on a Tricyciic Tempiate. J. Org. Chem. 2000, 65,4938-4943. 

Takeda, K. Stereospecific Cope rearrangement of the germacrene-type sesquiterpenes. Tetrahedron 97A, 30,1525-1534. 

The reactions of ( )- and (/)-/i-silylacryloylsilaries with lithium enolates of u, -unsaturated mefhyl ketones afford cis-5,6- and trflns-5,6-disubstituted 3-cyclohepte-nones, respectively (Scheme 10.227) [590, 591]. The observed stereospecificity in fhe [3-t4] annulation can be rationalized by a reaction mechanism via an anionic oxy-Cope rearrangement of the 1,2-divinylcyclopropane intermediate 161 generated by [2-1-1] annulation between the substrates. 

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