Natural products 1,2 -Wittig rearrangements

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

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) . 

In a cyclic system, the stereochemistry of the product of a [2,3]-Wittig rearrangement may be ensured by the rearrangement s suprafacial nature. [2,3]-Wittig rearrangement of lithiomethyl ethers derived from stannanes provides a valuable method for stereospecific... 

With a phenylsulfonyl group as X (Scheme 41) the intermediate, after rearrangement, will decompose directly to an aldehyde function, which reacts wiA excess alkyllithium to form an unsaturated alcohol. The often efficient transfer of chirality from C-1 of an optically active allylic alcohol to the newly created stereogenic centers at C-3 and/or C-4 is another valuable aspect of the 2,3-Wittig rearrangement which has already found extensive use in natural product synthesis. ... 

Along with the Claisen rearrangement, other related reactions are applicable for the preparation of natural products. For instance a [2.3]-Wittig reaiTangement is one step in the stereospecific synthesis of HMG-CoA reductase inhibitor pravastatin and in the total synthesis of the HMG-CoA synthase inhibitor 1233A according to the general scheme (equation 253). 

Any reaction that forms a bond between two prochiral atoms in a stereoselective manner is a valuable synthetic method. Some of the natural products that have been made in nonracemic form using the [2,3]-Wittig rearrangement as the key step are illustrated in Figure 6.7. The stereocenters formed in the Wittig rearrangement are indicated ( ). 

Another natural product, (+ )-faranal (27), a trail pheromone of the Pharaoh s ant, has also been synthesized starting with 2 (see Scheme 3) [11].The crucial transformation in the sequence is a [2,3] Wittig rearrangement of 24 which, after cw-hydrogenation, gives diene 25 in > 96% ee. This intermediate, when treated with potassium hydride, undergoes an anionic oxy-Cope rearrangement to afford the erythro aldehyde 26 in 91% ee. 

Smith employed a [2,3]-Wittig-Still rearrangement to install the trisubstituted (Z)-20-double bond in his group s total S5mthesis of (-)-hennoxazole A (100), an antiviral marine natural product. The transition state conformation 101a is similar to the ground state due to strain fScheme 17.161. 

Thomas and Hoegenauer achieved aliphatic 1,8-stereocontrol in the S5mthesis of racemic patulolide C 157 and epipatulolide C 158 via [2,3]-Wittig rearrangement of bisallylethers such as 160. ° The stereochemistry of the racemic product was confirmed by completion of the synthesis and comparison with natural epipatulolide C. Thomas reported several other... 

The imino [1,2]-Wittig rearrangement of hydroximates has also been employed in the construction of natural products. For example, ( )-cytoxazone (88) was prepared fi om intermediate 87, which was generated via [1,2]-Wittig rearrangement of 86. An asymmetric synthesis of (+)-... 

Complete chirality transfer from ciJ-ethers (96 equation 24) to homoallylic alcohols (97) was the cornerstone for numerous applications of the Wittig rearrangement in natural product synthesis (Table 9). The predictability of the absolute configuration of the reananged product on the basis of a suprafacial bond shift and the ready availability of optically active starting materials make these reactions attractive. 

Applications of the Claisen, Cope, and [2,3]-Wittig rearrangements in natural product synthesis including substrate-induced diastereoface-differentiation have been reviewed. ... 

---