Stork-Eschenmoser

Stork-Eschenmoser Hypothesis- Olefin Geometry is preserved in the cyclization reaction, i.e. trans olefin leads to a trans fused ring jucntion A. Eschenmoser HCA 1955, 38, 1890 G. Stork JAGS 1955, 77, 5068... 

An additional impetus for the development of biomimetic polyolefinic cyclizations was provided by the historically significant Stork-Eschenmoser hypothesis,4 a postulate that rationalizes the... 

Scheme 1, Enzyme-induced cyclizations of squalene oxide (2) (a) and the Stork-Eschenmoser hypothesis (b).

The tetracyclic alcohol 179 is produced by the action of boron trifluoride etherate or tin(IV) chloride on the oxirane 178 (equation 85)95. A similar cyclization of the oxirane 180 yields DL-<5-amyrin (181) (equation 86)96. In the SnCLt-catalysed ring-closure of the tetraene 182 to the all-fraws-tetracycle 183 (equation 87) seven asymmetric centres are created, yet only two of sixty-four possible racemates are formed97. It has been proposed that multiple ring-closures of this kind form the basis of the biosynthesis of steroids and tetra-and pentacyclic triterpenoids, the Stork-Eschenmoser hypothesis 98,99. Such biomimetic polyene cyclizations, e.g. the formation of lanosterol from squalene (equation 88), have been reviewed69,70. 

Fig. 29 Formation of isomeric decalins [71 ]—[73] by cyclization of a terpenoid alcohol catalysed by antibody HA5-19A4 raised to hapten [82]. The transition state [83a] has the leaving group in the equatorial position, as favoured by the Stork-Eschenmoser...

The idea that such cyclisations should be highly stereoselective derives from the Stork-Eschenmoser hypothesis, according to which the double bonds in polyalkenes of the squalene type are properly arranged to undergo cyclisation to fused polycyclic systems with the natural trans-anti-trans configuration. 

Despite extensive studies on acid-catalyzed diastereoselective polyene-cyclizations, their enantioselective behavior have not yet been reported. The stereochemical implications of polyene-cyclizations can be explained by the Stork-Eschenmoser hypothesis [140], and the most important feature required for an artificial cyclase is asymmetric induction during the initial protonation. Very recently, the author and Yamamoto et al. succeeded in the first enantioselective biomimetic cyclization of polypre-noids catalyzed by LB A [141]. 

In this chapter emphasis will be placed on preparatively useful procedures, the general rules which pertain in polyene cyclization, and the circumstances under which the Stork-Eschenmoser hypothesis is valid. The success, or otherwise, of polyalkene cyclization depends on a complex interplay between the... 

Formation of six-membered rings is the most common process in cation olefin cyclization. The initial cation is attacked by an olefin following Markovnikov s rule. Defined chairlike conformations in the transition state and the validity of the Stork Eschenmoser postulate9 allows the prediction of stereochemistry in a significant number of the cyclization products. 

Synthesis of frans-hydrindanes via bicyclization is effectively induced by a tetramethylallyl cation. The central double bond undergoes anti attack by the initial cation and the terminating nucleophile implying that E double bonds generate trans ring junctions and (Z)-olefins lead to the corresponding cis systems (Stork-Eschenmoser postulate)9. 

Mono- and bicyclizations can be carried out following a concerted mechanism provided the structural and electronic features allow such a reaction. In these cases the Stork-Eschenmoser postulate9 is valid. 

Very detailed mechanistic studies on polyene cyclisation have been pursued by Roger Snowden at Firmenich. [254] Cyclisation of the tricyclic system is initiated by terminal protonation, and anti-addition to the double bonds of the nascent six-membered rings occm-s from their chair conformations. Whether or not the cyclisation proceeds in a concerted manner, according to the Stork-Eschenmoser hypothesis, cannot be resolved from the experimental data. A stepwise process, in which the bond indicated in red is formed first, is equally conceivable. The following ring closure giving or 9b-epi-Ambrox is... 

A reaction called the Johnson polyene cyclization (based on the Stork-Eschenmoser hypothesis) converts triene A into the polycyclic molecule B. When first discovered, an initially formed carbocation at one end of the polyene reacted with a nearby alkene to form a ring containing a new cation. This reacted with another nearby alkene, etc. The reaction was plagued by low yields and formation of polymeric material and decomposition products. This transformation required many years to perfect and two improvements were the use of a cyclopentenol unit on the left to initiate the sequence, which became a cyclopentene unit, and an alkyne unit on the right to end the sequence by generating a methyl ketone. Briefly discuss why these two improvements helped the problems inherent to this reaction. 

According to the Stork-Eschenmoser hypothesis [lb, c], many polycyclic terpenoids such as hopene and lanosterol are biosynthesized via the site- and enantioselective protonation or epoxidation of a terminal olefin followed by diastereoselective x-cation cyclization [16]. Corey s group performed pioneering work on the cation-induced diastereoselective polycyclization of enantiopure epoxides [17]. For example, a very direct enantioselective total synthesis of members of the p-amyrin family of pentacyclic triterpenes has been developed by diastereoselective x-cation tricycli-zation reaction as a key step (Scheme 9.9) [17g]. 

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