Total synthesis applications

Hydrido(trialkylsilyl)silyllithiums, preparation, 3, 424 Hydroacylations, olefins, 10, 142 Hydroalkoxylations and etherification, 10, 672 in etherification, 10, 683 Hydroaluminations for C-E bond formation characteristics, 10, 857 chemoselectivity, 10, 859 mechanism, 10, 858 overview, 10, 839-870 stereoselectivity, 10, 861 total synthesis applications, 10, 865 characteristics, 3, 275 process and examples, 9, 268 via Ti(IV) complexes, 4, 658 Hydroaminations actinide-catalyzed, 4, 237 in aminations... 

Fig.1. Total synthesis applications of transition metal-promoted cycloadditions...

Scheme 5.53 Chiral ester-controlled domino cyclization and total synthesis application for (-h)-triptocallol.

Notable is the success of these transformations with labile aldehydes such as acrolein and 2-(benzyloxy)acetaldehyde, since these reactions produce bicyclic products (26 and 27) that contain useful functionality in the side chain as well as in the carbocyclic ring. This point will be illustrated later when we consider a total synthesis application of the hydrobenzofuran intermediate 27. 

Cephalosporanic acid, 3 -deacetoxy-, 7, 289 Cephalosporin, 3 -deacetoxy-absorption, 7, 293 synthesis, 7, 293 Cephalosporin, 3,4-dihydro-synthesis, 7, 292 Cephalosporin, 7a-hydroxy-synthesis, 7, 290 Cephalosporin C, 7, 288 as pharmaceutical, 1, 152 total synthesis, 7, 294 Woodward s total synthesis, 7, 294 Cephalosporin C, deacetoxy-synthesis, 7, 292 Cephalosporins, 7, 267, 285-298 7-acylamino substituent configuration, 7, 290 analogues synthesis, 7, 288 as antibiotics, 2, 519 3, 1038 application, 7, 296... 

Stereospecific Synthesis of Trisubstituted Olefins from Acetylenes or Aldehydes Applications to the Total Synthesis of Cecropia Juvenile Hormones (JH) and Farnesol... 

The first application of the Jacobsen-Katsuki epoxidation reaction to kinetic resolution of prochiral olefins was nicely displayed in the total synthesis of (+)-teretifolione B by Jacobsen in 1995. 

The intramolecular cycloaddition reaction of enamides has been exploited in alkaloid synthesis (81JOC3763). One successful application is provided by the total synthesis of the fused indolizidine 5 from 4 as a 1 1 mixture of epimers in 43% total yield 5 is a key intermediate in aspidosperma alkaloid synthesis (79JA3294). 

The preferred formation of 261 over 260 is in accord with the well-known positional order 3 > 2 for reactivity of unsubstituted indole. Aiming at total synthesis of leptosin alkaloids, an application of this methodology to the 1-hydroxy-L-tryptophan derivatives seems to be promising. 

The total synthesis of ( )-estrone [( )-1 ] by Vollhardt et al. is a novel extension of transition metal mediated alkyne cyclotrimeriza-tion technology. This remarkable total synthesis is achieved in only five steps from 2-methylcyclopentenone (19) in an overall yield of 22%. The most striking maneuver in this synthesis is, of course, the construction of tetracycle 13 from the comparatively simple diyne 16 by combining cobalt-mediated and ort/io-quinodimethane cycloaddition reactions. This achievement bodes well for future applications of this chemistry to the total synthesis of other natural products. 

Natural product total syntheses are particularly valuable when they are attended by the development of general utility methods of synthesis. In some instances, the successful completion of a natural product total synthesis requires the development and application of a new synthetic method. The total synthesis of erythronolide B by Corey et al. is one of these instances. The double activation macro-lactonization method was a fruitful innovation that was introduced in response to the challenge presented by the macrocyclic structures of the erythromycins. Several other methods to achieve the same objective, and numerous applications followed. 

Scheme 5. Applications of the Ni(u)/Cr(ii)-mediated coupling reaction to total synthesis.

Numerous applications of the Ni(n)/Cr(ii)-mediated coupling reaction in total synthesis have already been reported.11 Some of the more noteworthy examples derive from Kishi s laboratories and played a role in the syntheses of such complex molecules as (+)-ophiobolin C16 and halichondrin B17 (see Scheme 5). Another elegant application can be found in the enantioselective total syntheses of (+)-brefeldin C and 4-ep/-brefeldin C by Schreiber and Meyers (see Scheme 5).18... 

An impressive application of the (salen) Co-catalyzed intramolecular ARO of meso-epoxy alcohols in the context of total synthesis was reported recently by Danishefsky [33], Enantioselective desymmetrization of intermediate 9 by use of the cobalt acetate catalyst 8 at low temperatures afforded compound 10, which was obtained in 86% ee and >86% yield (Scheme 7.18). Straightforward manipulation of 10 eventually produced an intermediate that intersected Danishefsky s previ-... 

I11 Nicolaou s total synthesis of brevetoxin B, for example, out of the eleven transfused six- to eight-membered cyclic ethers, THP rings B, F, G, and I are constructed by application of this methodology through cydization of the appropriate... 

The addition of ( )-(3-trimcthylsilylallyl)boronate (10) to the racemic oxime 9 has been used in connection with a total synthesis of cannabisativine n. The results are congruent with the application of ( )-crotylboronatc as organometallic reagent9,, 0. The reaction is anti selective and generates the diastereomeric hydroxylamines 11 and 12, where 11 is converted to a tetrahydropyridine 13, a useful intermediate for the synthesis of cannabisativine11. 

We will focus on the development of ruthenium-based metathesis precatalysts with enhanced activity and applications to the metathesis of alkenes with nonstandard electronic properties. In the class of molybdenum complexes [7a,g,h] recent research was mainly directed to the development of homochi-ral precatalysts for enantioselective olefin metathesis. This aspect has recently been covered by Schrock and Hoveyda in a short review and will not be discussed here [8h]. In addition, several important special topics have recently been addressed by excellent reviews, e.g., the synthesis of medium-sized rings by RCM [8a], applications of olefin metathesis to carbohydrate chemistry [8b], cross metathesis [8c,d],enyne metathesis [8e,f], ring-rearrangement metathesis [8g], enantioselective metathesis [8h], and applications of metathesis in polymer chemistry (ADMET,ROMP) [8i,j]. Application of olefin metathesis to the total synthesis of complex natural products is covered in the contribution by Mulzer et al. in this volume. 

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