Natural product synthesis rearrangements

The Neber rearrangement has for example found application in natural product synthesis. 

The first reported use of the DPM rearrangement in natural product synthesis can be found in the synthesis of methyl chrysanthemate, 71, reported by Pattenden and Whybrow (Scheme 18)35. This is produced directly by photolysis of 1,4-diene 70. While it should be noted that this reaction gave 71 in only 12% yield, it did furnish the desired product in a single step, with the correct relative stereochemistry. Bullivant and Pattenden also used a DPM rearrangement to form an advanced intermediate in the synthesis of the dideoxy derivative of the sesquiterpene taylorione, 7436. Irradiation of 72 afforded 73 in 45% isolated yield this was then simply converted to 74 using standard transformations. 

These examples and many others illustrate the ongoing fascination with the Ferrier rearrangement. The growing catalog of catalysts and subtle variations in outcomes that are associated with these serve to enhance the practical utility of this reaction in glycoside and natural product synthesis. 

Applications of organocopper reagents and reactions to natural product synthesis are classified by reaction type conjugate addition, Sn2 substitution, Sn2 substitution, 1,2-metalate rearrangement, and carbocupration. 

Since the pioneering work by Sarel and co-workers on the iron carbonyl promoted transformation of vinylcyclopropanes and related compounds [1], a variety of transition metal complexes have been examined to achieve effective activation of the vinylcyclopropane-cyclopentene rearrangement which usually requires pyrolytic conditions. These reactions have been applied to natural product synthesis in some cases and have already been reviewed in several excellent articles [2-4]. 

Snider and colleagues have developed the sequential ene reaction/thia-[2,3]-Wittig reaction which provide appropriately functionalized product 152 at allylic position on simple alkene 150 in two steps involving intermediate 151 (equation 87) . Thia-[2,3]-Wittig rearrangement was often utilized as a key step of natural product synthesis. Masaki and colleagues have demonstrated that the potassium enolate thia-[2,3]-rearrangement of aUyl sulfide 153 to 154 is useful for the synthesis of terpenoid diol component 155 of the pheromonal secretion of the queen butterfly (equation 88) . 

These reactions involve metallate rearrangements , migratory insertion and transition metal-catalysed vinylic substitution reactions. They also perform well in applications in natural product synthesis . Many useful synthetic possibilities arise from application of ring-closing olefin metathesis (RCM) to unsaturated homoaldol products and their derivatives by means of the Grubbs catalyst 3942 4-286 Equation 105 presents some examples. ... 

Experimental details for the previously reported synthesis of ( )-bakkenolide-A (411) (syn. fukinanolide) have been provided in a recent paper which also describes the potential of [2,3]sigmatropic rearrangement in natural product synthesis. In the particular case of bakkenolide-A the correct configuration at C-7 is achieved by [2,3]sigmatropic rearrangement of the intermediate (409) (cf. Vol. 5, p. 85). A... 

Mat Robinson was born in Malvern he graduated from the University of Wales Swansea with a first class M.Chem. degree in 2004. He is also currently studying there for his Ph.D. under the supervision of Dr. Andy Graham. His research interests include the development of novel solid Lewis and Bronsted acids, nanomaterials, and rearrangement reactions in natural product synthesis. 

K. Tadano, Natural product synthesis starting with carbohydrates based on the Claisen rearrangement protocol, in Studies in Natural Products Chemistry, Atta-ur Rahman, ed., Elsevier Science, New York, 1992, pp. 405-455. 

This chapter summarizes three related and highly effective approaches to the catalytic asymmetric generation of quaternary stereocenters - organocatalytic rearrangements of O-acyl azlactones to their C-acylated isomers and analogous isomer-izations of O-acyl oxindoles and O-acyl benzofuranones. All three processes hold great promise for application in, e.g., natural product synthesis [91-93],... 

Enzymatic Baeyer-Villiger oxidations have been studied for a long time some very useful applications in natural product synthesis date back more than two decades. For example, prochiral (3A, 5,S )-4-hydroxy-3,5-dimethylcyclohexanone was successfully oxidized using a CHMO from Acinetobacter sp. NCIMB 9871. In this case the seven-membered ring formed rearranges spontaneously into the thermodynamically more stable y-lactone. The rearranged lactone has been used in the synthesis of natural products such as tirandamycin or calyculin A (Fig. 25) [157-159],... 

This rearrangement-cyclization cascade was applied to natural products synthesis. For example, DDQ oxidation of the appropriate dihydro-3 (27T)-furanone enol acetates (Table 3.5, entries 1 and 7) afforded bullatenone and the antitumor agent geiparvarin in a very rapid route (Fig. 3.1).69 70... 

Although prolonged heating of the pyrroline (192) does not lead to further ring expansion, a second cyclopropylimine rearrangement takes place on heating in the presence of anhydrous hydrobromic acid at 140°C for 10 min, giving after hydrolysis the pyrrolizidinone (193) (equation 128). This sequence opens a route to pyrrolizidines that are of obvious interest in natural product synthesis. 

A Wagner-Meerwein rearrangement via a bridged carbenium ion has been observed in the electrodecarboxylation of bicyclo[2.2.1]heptane-2-carboxylic acids (CXVIIa, CXVIIb, and CXVIIc), leading to the formation of the same products (CXVIII and CXIX) [Eq. (58)] [174]. This method has been successfully applied to synthesis of useful intermediates for natural product synthesis. Some examples are given in Eqs. (59) and (60) [175-179]. 

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