Natural products boron mediation

Recently the use of the boron trifluoride catalysed reaction in the synthesis of the oxazolylindole fragment 25 of the natural product diazonamide A has been reported.<96SL609> Thus the BF3-mediated reaction of the indolyl diazoketoester with acetonitrile gave oxazole 25 with simultaneous removal of the Boc-protecting group (Scheme... 

The same natural product was synthesized by Paterson et al. [45] who assembled the carbon skeleton of the macrolide from three larger subunits as well. Instead of the Evans-Metternich variant they used their boron-mediated antz-selective aldol strategy which relies as the Evans-Metternich aldol on stereo-induction from the a-chiral center and translates the E-enolate geometry, established due to the use of Cy2BCl, to the anti aldol product (Scheme 33). 

The asymmetric total synthesis of cytotoxic natural product (-)-FRI 82877 was accomplished by D.A. Evans and co-workers." " To establish the absolute stereochemistry, a boron mediated aldol reaction was utilized applying (R)-4-benzyl-A/-propionyl-2-oxazolidinone" as a chiral auxiliary to yield the syn aldol product. 

The intramolecular Ullmann condensation was used by D.L. Boqer and co-workers to form the 15-membered macrocyclic ring of the cytotoxic natural product, combretastatin D-2. This compound possesses unusual meta- and paracyciophane subunits, which are also found in a range of antitumor antibiotics. The first approach where the final step was a macrolactonization was unsuccessful, so the researchers chose to form the biaryl ether moiety as the key macrocyciization step. Methyicopper was found to mediate the cyclization and gave moderate yield of the corresponding biaryi ether. Finaiiy boron triiodide mediated demethylation afforded the natural product. 

Application of the external chiral boron reagent (90) in the totd synthesis of bryostatin, a natural product, is shown in Scheme 45. The convergent approach adopted involves coupling of the boron enolate derived from (111) with aldehyde (112). The reaction mediated by an achiral boron reagent (Et2BOTf) provides only a 2 1 preference for the formation of the desired isomer (115) in adduct (113). The use of chiral (2/ ,5 )-dimethylborolanyl triflate in this reaction increases the selectivity to a 6 1 preference as... 

Since the early success of Decicco et al. [19] in extending the boronic acid cross-coupling to an intramolecular system, more examples of this approach have appeared in the literature (Scheme 5.5). Snapper and Hoveyda reported a total synthesis of the anti-HIV natural product chloropeptin 1 in which the crucial biaryl ether moiety was constructed via the Cu-mediated reaction (Scheme 5.5) [20]. Thus, treatment of the boronic ester 10 with NalO liberates the boronic acid, which then cyclizes under Cu(OAc)2 to give the biaryl ether 11, a precursor to the final target. In this case, the addition of 10 equiv. of methanol was critical for efficient intramolecular cross[Pg.210]

Thus, boron enolates prepared under mild conditions enable aldol-type reactions essentially under neutral conditions. Stereocontrolled synthesis of acyclic molecules has been achieved by employing boron enolate-mediated aldol reactions this method has been extensively applied to the synthesis of natural products. 

The method was successfully applied to get access to enantiomerically pure building blocks for total syntheses [127, 128], among whose that of the polyene macrolide RK-397, carried out by Denmark and Fujimori, may serve as an illustrative example (Scheme 5.73). An early step of the synthesis is a vinylogous aldol reaction between dienolate 255 and sdylacroleine 256, mediated by silicon tetrachloride and bisphosphoramide 235. The aldol adduct 257, obtained in 96% ee, was transformed over several steps into the boron enolate 258 that was added diastereoselectively in a further aldol reaction to the aldehyde 259 to give the C19-C31 fragment 260 of the natural product RK-397 [127]. 

BORON-MEDIATED ASYMMETRIC ALDOL REACTIONS FOR THE CONVERGENT SYNTHESIS OF NATURAL PRODUCTS... 

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