Lewis acids polyene cyclization

Acidic resins [1, 514, after citation of ref. 17]. The biogenetically patterned cyclization of polyenes by Lewis acid catalysts can also be effected by cation-exchange resins (Amberlite IR-20 and XE-100).17a Thus methyl trans.trans-iarntsate (1) is cyclized by XE-100 in acetic acid to (2), (3), and (4), separable by gas chroma-... 

Polyene cyclization. The catalyst enables an efficient synthesis of precursors of taxodione. It is vastly more effective than BFj OEt2 or other Lewis acids. 

A spectacular example of cationic cyclization is the Johnson polyene cyclization, described in Section 10.8.A. Polyenes such as squalene are expected to assume a steroid-like conformation in the lowest energy form (sec. 1.5.E), based on the biogenetic preparation of cholesterol from squalene. In practice, treatment of polyenes with acid led to a very low yield of tri- or tetracyclic products, giving instead significant amounts of polymeric material. Diligent work over many years prevailed, however, and Johnson solved the many problems (as described in sec. 10.8.A) to make this reaction an excellent and efficient synthetic route to di-, tri-, and tetracyclic molecules. One of the later examples of polyene cyclization uses an allyl silane to quench the cyclization process. A Lewis acid was used to initiate the reaction via reaction with the acetal. Treatment of... 

Electrocyclic reactions are not limited to neutral polyenes. The cyclization of a pentadienyl cation to a cyclopentenyl cation offers a useful entry to five-membered carbocycUc compounds. One such reaction is the Nazarov cyclization of divinyl ketones. Protonation or Lewis acid complexation of the oxygen atom of the carbonyl group of a divinyl ketone generates a pentadienyl cation. This cation undergoes electrocyclization to give an allyl cation within a cyclopentane ring. The allyl cation can lose a proton or be trapped, for example by a nucleophile. Proton loss occurs to give the thermodynamically more stable alkene and subsequent keto-enol tautomerism leads to the typical Nazarov product, a cyclopentenone (3.220). 

Smith s group has reported in full on the Lewis-acid promoted annulation of unsaturated diazoketones leading to cyclopentenones in variable, but often good, yields (Scheme 6). The method can also be applied to polyene cyclizations as in the conversion of diazoketone (81) to (82) in 43% yield (cf. refs. 71, 92, and... 

In contrast to (Lewis) acid-catalysed annulations of /3-keto-esters such as (222), which lead to decalins cf. refs. 175,176), mercuric ion-induced cyclization of (222) leads instead to the pyran (223). Further examples of the ability of a carbon-tin bond to provide a specific nucleophilic site in TiCU-catalysed cyclizations of allylic alcohols have been reported, together with a full account of the use of an imino group to initiate polyene cyclizations annulations of imines that carry a chiral substituent result in moderate chiral inductions. 

How much of the biosynthetic operation can one expect to simulate in the organic laboratory The first studies directed toward nonenzymatic bio-genetic-like polyene cyclization were not promising. However, van Tamelen found that if the D-ring is preformed, the isoeuphenol system can be obtained in good yield by treatment of the epoxide precursor with a Lewis acid (207). 

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. 

In 2010, Loh s group reported a highly efficient catalytic enantioselective polyene cyclization [52]. An a-ketoester was demonstrated to initiate enantioselective cationic polyene cyclization catalyzed by a Sc(OTf)3-Pybox Lewis acid catalyst (Scheme 9.39). 

After total synthesis of rhododaurichromanic acid by photochemical [2+2] cycloaddition, inspired by the precedents in polyene cyclizations, especially the work of Omura and coworkers [74], we attempted to treat daurichromenic ester 118a with various Lewis acids and mercury reagents but failed, as shown in Scheme 12.28. Fortunately, the outcome changed when using Brpnsted acids such as TFA, especially when it was used at 30 equiv or as a cosolvent with CH2CI2, we isolated two products 121 and 122 with each as a single diastereomer, the formation of 122 likely proceeds through the classic polyene cyclization via 123 [75]. 

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