Terpenes, Wagner-Meerwein rearrangement

Of synthetic importance is the Wagner-Meerwein rearrangement especially in the chemistry of terpenes and related compounds." For example isoborneol 5 can be dehydrated and rearranged under acidic conditions to yield camphene 6 ... 

Except for terpene chemistry, the Wagner-Meerwein rearrangement is of limited synthetic importance. It is rather found as an undesired side-reaction with other reactions, for example in the synthesis of alkenes by elimination reactions. 

Wagner-Meerwein rearrangements were first discovered in the bicyclic terpenes. 

Principal terpene alcohol components of pine oils are a-terpineol, y-terpineol, p-terpineol, a-fenchol, bomeol, terpinen-l-ol, and terpinen-4-ol. The ethers, 1,4- and 1,8-cineole, are also formed by cydization of the y>-menthane-1,4- and 1,8-diols. The bicydic alcohols, a-fenchol [512-13-0] (61) and bomeol (62), are also formed by the Wagner-Meerwein rearrangement of the pinanyl carbonium ion and subsequent hydration. Bomeol is t / i7< -l,7,7-trimethylbicydo[2.2.1]heptan-2-ol [507-70-0]. Many other components of pine oils are also found, depending on the source of the turpentine used and the method of production. 

Wagner-Meerwein rearrangements were first discovered in the bicyclic terpenes, and most of the early development of this reaction was with these compounds.81 An example is... 

Cyclization reactions of GGPP mediated by car-bocation formation, plus the potential for Wagner -Meerwein rearrangements, will allow many structural variants of diterpenoids to be produced. The toxic principle taxine from common yew (Taxus baccata Taxaceae) has been shown to be a mixture of at least eleven compounds based on the taxadiene skeleton which can be readily rationalized as in Figure 5.43, employing the same mechanistic principles as seen with mono- and sesqui-terpenes. 

Rearrangement of the primary halide product (Wagner-Meerwein rearrangement) occurs when HC1 or HBr is added to bicyclic terpenes, especially in solvents of high dielectric constant and when an excess of hydrogen halide is used. For the mechanism see Gould.18d... 

Wagner-Meerwein rearrangements occur extremely frequently among branched-chain aliphatic and alkylaryl compounds, and are particularly important in the terpene and camphor series. An example of rearrangement of type a) is that of camphene hydrochloride (1) into isobornyl chloride (2), for which Meerwein and van Emster141 give the following directions ... 

This particular type of Wagner-Meerwein shift has special recognition due to its importance in the field of terpene chemistry. For example, the conversion of a-methylcamphene into 4-methylisoborneol involves both a Nametkin and a Wagner-Meerwein rearrangement. In the Meinwald rearrangement both 1,2- and 1,3-shifts occur to give different products (Scheme 2.24). 

In 1921, Leopold Ruzicka (1887-1976) established the isoprene rule for the biosynthesis of terpenes through a formal head-to-tail coupling of isoprene units. Deviations from the rule (as in the case of chrysanthemic acid), as well as Wagner-Meerwein rearrangements, occasionally complicate the analysis. Only in the mid-1950s it could be shown that terpenes are indeed formed by active isoprene emits . [24,25]... 

Wagner-Meerwein rearrangements are prevalent in the biosynthesis of terpenoids and steroids [21], An example can be represented by the concerted rearrangements (1,3-hydride and 1,2-methyl shift) that lead to the biosynthesis of trichodiene, an intermediate of the terpenes verrucarin A and roridin A (Section 3.2.24) (Figure 1.18). 

Wagner-Meerwein type rearrangements have also been widely reported in terpene chemistry [127, 128]. One well-known transformations involves the... 

Terpene synthesis in nature is a complex process involving successive electrophilic additions followed by a variety of skeletal rearrangements, including those of the Wagner-Meerwein variety. These reactions are typically catalyzed by enzymes and are responsible for the wide array of structural diversity in these compounds, including 6-6-6-5 tetracycles, 6-6-6-6-5 pentacycles, 6-6-6-6-6 pentacycles, and the less abundant acyclic, monocyclic, bicyclic, tricyclic, and hexacyclic triterpenoids. Each of the more than 100 triterpene skeletons identified in nature are formed through the involvement of several multifunctional triterpene synthases. 

Many of the most interesting rearrangements involving 1,2-shifts were discovered during structural studies of naturally occurring compounds such as terpenes by H. Meerwein and G. Wagner. 

Thousands of different terpene structures occur in perfume ingredients, both natural and synthetic. The chemistry of terpenes is rich and varied and attempts to understand it have, on many occasions, contributed fundamentally to our total understanding of chemistry. One example is the work of Wagner and Meerwein, whose studies in terpene chemistry led, amongst many discoveries, to elucidation of the rearrangement that bears their names. This work made a very significant contribution to our fundamental understanding of the properties... 

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