Mniopetal E synthesis

The results of the thermal IMDA reactions using the substrates 88-96 are summarized in Scheme 16 and Table 4. We did not conduct the IMDA reactions of 88-96 using a Lewis acid catalyst because of our previous unfruitful results with Lewis acids obtained in the mniopetal E synthesis. Each solution of the substrate in toluene was heated at 210 °C in a sealed tube in the presence of a catalytic amount of BHT. After purification of the reaction mixture by silica gel column chromatography, the diastereomeric ratios (endo/exo and A/B) of the... 

In summary, we completed the first total synthesis of (-)-mniopetal E (5), a prototype of mniopetals A-D, in its natural form. Our synthesis featured the following aspects (1) the substrate 62 for the IMDA reaction was synthesized in enantiopure form from the known building block 19, and (2) the stereoselective IMDA reaction of 62 under thermal conditions realized practical access to the desired ercdo-cycloadduct 63-A possessing the entire carbon skeleton with the correct stereochemistry. Our total synthesis of 5 as the natural form established the unsettled absolute configuration. 

As the total synthesis of mniopetal E (5) was compleated, we next focused our attention on mniopetal F (6) and kuehneromycin A (7) as synthetic targets. The retrosynthesis of 6 and 7 is shown in Scheme 13. We anticipated that the IMDA reaction of the substrate G would proceed favorably via a chair-like enrfo-transition state F, which would lead to the desired adduct E. In general, a substituent neighboring the dienophile part would dispose of the sterically less-demanding equatorial orientation in the transition state. However, the trialkyl-... 

Jauch achieved the short and elegant total synthesis of mniopetals during almost the same period in which our total syntheses were reported [36-41]. We briefly introduce Jauch s achievements on this subject. The key step of his synthesis was the IMDA reaction of 2-substituted butenolide 124 (Scheme 20), which was prepared by the diastereoselective PhSeLi-induced Baylis-Hillman reaction of 122 and Feringa s butenolide 123 [99]. The cycloadduct of this IMDA reaction 125 was transformed into kuehneromycin A and mniopetals E and F, respectively. 

The total synthesis of mniopetal E (5) was achieved in a six-step sequence from the cycloadduct 125 (Scheme 21). The treatment of 125 with trifluoromethanesulfonic anhydride (Tf20) afforded triflate 129. Elimination of trifluoromethanesulfonic acid to introduce a double bond was accomplished in 2,6-lutidine at 100 °C, giving 130 in 84% yield. Deprotection of TBDPS ether was followed by Parikh-Doering oxidation of the resulting 131 by the same procedure used in the case of 127. Taking advantage of the electron-rich double bond between C-l... 

Jauch, J., Synthetic studies towards mniopetals. Part 2. A short synthesis of mniopetal E, Synlett, 87,... 

There are many synthetic applications in the recent literature. The most common application is the oxidation of primary alcohols where the substrate can tolerate only a narrow range of reaction conditions or is part of a highly functionalized molecule. 26 Secondary alcohols can also be oxidized under very mild conditions. A synthetic example is taken from Tadano s synthesis of (-)-mniopetal E, 27 in which the primary alcohol unit in 79 was oxidized to the aldehyde unit in 80. 

We conclude with two synthesis that include both y- and a -selective extended enolate chemistry 45 The first is of of mniopetal F. The Horner-Wadsworth-Emmons reaction of 168 (cf. 29) prepared by y-bromination of an extended enol with the appropriate aldehyde gives the triene 169 with good (>20 1) E Z selectivity and of course total y-selectivity. This is converted into 170. 

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