Synthetic Scope

The selective insertion of diphenylacetylene in the cyciopaiiadated sulfide complex 1 leads to the stable organometallic complex 2, which can be depalladated with silver(I) tetrafluoroborate to give a mixture of the dibenzothiepinium salt 3 and the dibenzo[Z>,z ]thiepin 4.91 Demethyla-tion of 3 to yield 4 is complete after refluxing overnight in chlorobenzene. The synthetic scope of this method for thiepin derivatives is limited due to their thermal instability, but the method is very suitable for the synthesis of 1//-2-benzothiopyrans.91... 

The synthetic scope of radical cyclizations can be further extended by tandem trapping by electrophilic alkene. 

In carrying out kinetic resolution, these in the standard approach are limited to 50% yield regarding the racemate. However, different approaches were developed [28] to overcome this limitation. The classical standard solution is to reracemize the unconverted enantiomer. A more advanced solution is the establishment of a dynamic kinetic resolution that has considerably expanded the synthetic scope of chemical processes. Here, the unconverted enantiomer is, in contrast to the latter method, racemized in situ. A great number of novel enzymatic methods have been developed [29]. Within this chapter, process solutions for enzymatic resolutions of racemic mixtures will be highlighted. 

Recently, ///)H.YL has been found to catalyze the stereoselective addition of nitroalkanes to aldehydes in an. S -selective fashion, which is in agreement with the known stereopreference of this enzyme. This is the first example for a substitution of HCN by another carbon nucleophile, expanding the synthetic scope of this biocatalytic transformation. The addition of nitromethane to different aldehydes with moderate to good yields and enantioselectivity has been demonstrated (Figure 5.9) [58]. However, large amounts of enzyme are required to... 

The mechanism and synthetic scope of the reactions of monohapto y -and -propargyliron complexes have been described earlier (see Schemes 30-33 in Section IV,A,2).61 An example of the synthesis of isothiazolines is given in Scheme 116.178 Unfortunately, yields are either low or unspec-... 

Homo-coupling of vinylic mercurials occurs readily under palladium195 or rhodium196 catalysis, but with the stoichoimetric amount of a reagent (equation 111)195. Divinylpal-ladium intermediates may be involved in this reaction. This reaction is also of limited synthetic scope since organomercurials are usually prepared via vinylboranes, which... 

Figure 2-3. Synthetic scope of the SAMP/RAMP-hydrazone method.

Cyclization reactions utilizing a vinyl sulfide group were also examined (Scheme 34) [46], This substrate was chosen for study because, like the methyl substituents used earlier, the sulfide would have a favorable conformational effect on the substrate and would serve as an electron-donating group for making the olefin more nucleophilic. Unlike the methyl substituent, the use of the sulfide led to a carbonyl product that could then be used to further elaborate the cyclized product. Hence, the success of the vinyl sulfide-based cyclization reaction served to extend the synthetic scope of these reactions. 

Organocopper chemistry is still rapidly expanding its synthetic scope. The scope of carbocupration, previously limited to acetylenes, has recently been extended to olefins [33-36]. 1,6-, 1,8-, 1,10-, and 1,12-Addition and 1,5-5 2" substitution reac-... 

Optically active epoxides are important building blocks in asymmetric synthesis of natural products and biologically active compounds. Therefore, enantio-selective epoxidation of olefins has been a subject of intensive research in the last years. The Sharpless [56] and Jacobsen [129] epoxidations are, to date, the most efficient metal-catalyzed asymmetric oxidation of olefins with broad synthetic scope. Oxidative enzymes have also been successfully utilized for the synthesis of optically active epoxides. Among the peroxidases, only CPO accepts a broad spectrum of olefinic substrates for enantioselective epoxidation (Eq. 6), as shown in Table 8. 

The introduction of these alternative approaches has permitted the direct trans-ferral and smooth integration of many versatile solution phase reagents from mainstream chemistry catalogues straight into practical protocols for use in com-hinatorial parallel hbrary generation thus broadening the amenable chemistry base. As with aU procedures it is the flexibihty and synthetic scope provided by these simple operations that has enhanced their utility as alternative reaction conditions and purification strategies. 

Zhou and Hartwig recently discovered the beneficial effect of added potassium hexamethyldisilazanide (KHMDS) base for the asymmetric addition of aniUnes to norbornenes, thereby widening the synthetic scope of the original CMM system (see Table 6.2) [17]. [IrCl(COE)2]2 and two equivalents of variants of the Segphos and Biphep Ugands first presumably form complexes 8, 11, and 12 in situ (see Chart 1) and then in combination with co-catalytic KHMDS generate the catalytically active species (see Table 6.2 and Section 6.4 for a discussion of the mechanism). 

Iridium-Catalyzed Olefin Hydroamination (OHA) 151 Table 6.2 Widening the synthetic scope of the CMM system. 

Preliminary efforts to examine the mechanism of C-H amination proved inconclusive with respect to the intermediacy of carbamoyl iminoiodinane 12. Control experiments in which carbamate 11 and PhI(OAc)2 were heated in CD2CI2 at 40°C with and without MgO gave no indication of a reaction between substrate and oxidant by NMR. In Hne with these observations, synthesis of a carbamate-derived iodinane has remained elusive. The inability to prepare iminoiodinane reagents from carbamate esters precluded their evaluation in catalytic nitrene transfer chemistry. By employing the PhI(OAc)2/MgO conditions, however, 1° carbamates can now serve as effective N-atom sources. The synthetic scope of metal-catalyzed C-H amination processes is thus expanded considerably as a result of this invention. Details of the reaction mechanism for this rhodium-mediated intramolecular oxidation are presented in Section 17.8. 

A third approach to the generation of PINO from HPI is the one first described by Ishii and coworkers" and subsequently followed by Minisci and coworkers" for synthetically useful transformations of alcohols or other H-donor substrates into carbonyl derivatives. It entails the use of catalytic amounts of a Co(II) salt, usually Co(OAc)2, with O2 in the presence of m-Cl-benzoic acid (MCBA)". The synthetic scope of this procedure will be commented on later, but it is sufficient to point out here that PINO is produced from HPI in a catalytic cycle through a short-living Co(III) oxidizing intermediate ... 

The stability of the heterocyclic ring, particularly to oxidation, allows a wide range of substituent group interconversions to be carried out thus providing access to numerous derivatives. Indeed, the preferred route to a particular compound may often be by manipulation of a readily accessible analogue, rather by building the substituent into the precursor. The reader is referred to Section 4.05.7 for illustrations of the synthetic scope such reactions afford for all the 1,2,5-oxadiazole systems under review. 

SYNTHETIC SCOPE OF THE CYCLOPROPANATION USING ZINC CARBENOIDS. 246... 

The present method of preparation is that described by Bruggink and McKillop.4 It has the particular advantages of high yield and manipulative simplicity, and avoids the problem inherent in Hurt-ley s procedure of separation of mixtures of carboxylic acids by fractional crystallization or column chromatography. The method is, moreover, of wide applicability with respect to both the /3-dicarbonyl compound and the 2-bromobenzoic acid. The synthetic scope and limitations of this procedure for the direct arylation of... 

Arynic substitution is a versatile technique of functional group transformation in aromatic systems and has found varied applications in preparation of simple compounds and in multi-step synthesis.3 4,3 The present section comprises examples illustrative of its synthetic scope. Attention is also drawn to some allied strategies which, when used in conjunction with the nucleophilic coupling of arynes, have opened convenient routes to complex natural products. 

Considerable synthetic scope exists for the application of diene-based and ene-yne-based ring-closing metathesis reactions to the synthesis of 1,3-oxazepine and 1,3-thiazepine derivatives. Particular emphasis on type e reactions is likely to be very fruitful. 

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