Polyene-type cyclizations

A series of carbocyclization cascades of allyl ketenimines initiated through a thermal aza-Claisen rearrangement of A-phosphoryl-A-allyl ynamides has been reported where interceptions of the cationic intermediate via Meerwein-Wagner rearrangements and polyene-type cyclizations are observed (Scheme 17) ... 

A radical-cation-type cyclization of a series of isoprenoid polyene acetates has been described recently by Demuth. In the presence of an electron acceptor... 

Polyene Heck-type cyclization,3 Overman s group has reported bicyclization of trienyl triflates to spirobicyclic systems in the presence of Pd(OAc)2/P(C6H5)3 (1 4) and 2 equiv. of N(C2H5)3. Under these conditions 1 cyclizes to 2 in 72% yield. This cyclization is particularly facile when catalyzed by Pd(OAc)2 and (R,R)- or (S,S)-DIOP (4, 273) in a 1 1 ratio. In this case, the tricyclic dienone (2) is obtained in... 

Woodward and Hoffmann have first disclosed that the thermal (4M+2)-cyclization (and also the photochemical (4M)-cyclization) takes place via Type I process, and the photochemical (4m+2)-cyclization (and also the thermal (4m)-cyclization) via Type II process 51>. They called the former (Type I) process "disrotatory", while the latter (Type II) process was referred to as "conrotatory". They attributed this difference in selectivity to the symmetry of HO and SO MO in the ground-state and excited-state polyene molecules, respectively (Fig. 7.33). The former is symmetric with respect to the middle of the chain, and the latter antisymmetric, so that the intramolecular overlapping of the end regions having the same sign might lead to the Type I and Type II interactions, respectively. 

Polyene cyclizations have been of substantial value in the synthesis of polycyclic natural products of the terpene type. These syntheses resemble the processes by which terpenoid and steroidal compounds are assembled in nature. The most dramatic example of biological synthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, the enzyme presumably functions not only to induce the cationic cyclization but also to bind the substrate in a conformation corresponding to the stereochemistry of the polycyclic product.21... 

This review covers the biosynthesis of terrestriai and marine polyethers and discusses their biologic properties and the molecular genetics and enzymology of the proteins responsible for their formation. The biosynthesis of monensin, nanchangmycin, nonactin, and the marine polyether ladders are discussed in detail. Novel enzymes found only in type I polyketide polyether gene clusters that are responsible for the epoxidation and cyclization of polyene biosynthetic intermediates are described. The macrotetrolide biosynthetic gene cluster, which is an ACP-less type II polyketide synthase that functions noniteratively is reviewed. 

Johnson, W.S., Newton, C., and Lindell, S.D., The carboalkoxyallylsilane terminator for biomimetic polyene cyclizations. A route to 21-hydroxyprogesterone types. Tetrahedron Lett.. 27, 6027, 1986. 

Although the overall yield was modest, an interesting point was elucidated concerning this type of reaction. The polyene 95, although deviating substantially from the pattern of squalene-like disposition of methyl substituents previously studied and in no way simulating a natural intermediate, still cyclizes in significant amounts to a tetracyclic system. 

Prestwick and Labovitz s ° recent total synthesis of serratenediol is based on a biogenetic type polyene cyclization of the tetraenic alochol 208. 

Heck-type polyene cyclization —, asym. 43,660 Polyenenitriles 43, 309 Polyethers... 

In their now classic monograph [1], Wooodward and Hoffmann concentrate on three basic types of no mechanism reaction Electrocyclic reactions -notably polyene cyclizations, cycloadditions, and sigmatropic rearrangements. These three reaction types will be taken up in this and the next two chapters from the viewpoint of Orbital Correspondence Analysis in Maximum Symmetry (OCAMS) [2, 3, 4], the formalism of which follows naturally from that developed in Chapter 4. The similarities to the original WH-LHA approach [5, 6], and the points at which OCAMS departs from it, will be illustrated. In addition, a few related concepts, such as allowedness and forbiddenness , global vs. local symmetry, and concertedness and synchronicity , will be taken up where appropriate. 

Miscellaneous. The cyclization of synthetic polyene epoxides provides a useful biogenetic-type chemical route to tetra- and penta-cyclic natural products. Thus the epoxide (478) has been used in the total synthesis of isoeuphenol, 24,25-dihydro-A < >-protosterol, and 24,25-dihydroparkeol, ... 

The synthesis in Scheme 13.38 combines elements of a biomimetic-type polyene cyclization with a rearrangement similar to that just described in Scheme 13.37. The early stages of the synthesis culminate in the construction of the allylic alcohol in step B. In step C, it is epoxidized using the stereoselective VO(t-BuOOH) method (Section 12.2.1). This epoxidation provides the key intermediate for the polyene cyclization. The mild Lewis acid FeCla is used to promote the cyclization, which terminates in an electrophilic substitution of the methoxyphenyl substituent. Steps E and F convert the methoxyphenyl ring to a diene. This diene undergoes a Diels-Alder reaction in step G. After catalytic reduction of the double bond, the anhydride is subjected to an oxidative bis-decarboxylation (see Section 12.4.2 for discussion of this reaction). The resulting alkene is epoxidized, and the epoxide is reduced. A rearrangement is done at this point. The reaction is similar to that used in Scheme 13.37, except that it involves a saturated, rather than allylic, system. The final steps in the synthesis are those used in Schemes 13.33 and 13.34. 

The first way involves activation of an internal double bond by an electron-supplying jt-attachment [21b]. This type of process is quite useful, as is demonstrated by the especially simple, enantioselective syntheses of three well-known natural products. Thus, (-i-)-dysideapalaunic acid, dehydroabietic acid, and 4-epipodocarpic acid were synthesized through very short pathways including an enantioselective polyene cyclization under the influence of the LBA at -78°C for 15 min (Scheme 9.50). 

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