Aryl halides naturally occurring

Carbonylation of halides in the presence of primary and secondary amines at I atm affords amides[351j. The intramolecular carbonylation of an aryl bromide which has amino group affords a lactam and has been used for the synthesis of the isoquinoline alkaloid 498(352], The naturally occurring seven-membered lactam 499 (tomaymycin, neothramycin) is prepared by this method(353]. The a-methylene-d-lactam 500 is formed by the intramolecular carbonylation of 2-bromo-3-alkylamino-l-propene(354]. 

FIGURE 23 1 Some naturally occurring aryl halides... 

Some aryl halides occur naturally but most are the products of organic synthesis The methods by which aryl halides are prepared were recalled m Table 23 2... 

The direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls (Scheme 1-41) [147]. The synthesis of biaryls is readily carried out in the same flask when the first coupling of the triflate with diboron 82 is followed by the next reaction with another triflate. The synthesis of naturally occurring biflavanoids and the couphng of N-(phenylfluorenyl)amino carbonyl compounds to polymeric supports are reported [154]. 

The two main methods for the preparation of aryl halides, halogenation of arenes by electrophilic aromatic substitution and preparation by way of aryl diazonium salts, were described earlier and are reviewed in Table 23.2. A number of aryl halides occur naturally, some of which are shown in Figure 23.1. 

Until recently no satisfactory procedure for the direct conversion of a primary aliphatic amine into an alkyl halide was available. This contrasts sharply with the ready conversion of primary aromatic amines into aryl halides via the diazonium salt (Section 6.7, p.922). However a useful method has not been discovered which is not only applicable to the synthesis of simple alkyl and aralkyl chlorides, bromides, iodides and fluorides, but could clearly be of value when it is required to replace an amino group in a naturally occurring amine by a halogen.92... 

In naturally occurring LDHs, the most commonly found interlayer anion is carbonate. In practice, however, there is no significant restriction to the identity of the charge balancing anion that can occupy the interlayer region. Examples include inorganic (such as halides, oxo-anions, silicates and polyoxometalates) as well as organic anions (such as alkyl or aryl carboxylates and sulfonates). 

Observations of these reactions in the natural environment indicate that they take place on the order of years per chlorine removed for aryl halides in sediments (Brown et al., 1987 Adriaens et al., 1999 Fu et al., 2001 Gaus et al., 2002), and months to years for alkyl halides or pesticides in groundwater (Potter and Carpenter, 1995 Wiedemeier et al., 1999 Skubal et al., 2001). Accurate calculations account for the metabolic rates measured in sediments or soils (Henrichs and Reeburgh, 1987 Schlesinger, 1991 Murphy and Schramke, 1998). For example, Fu et al. (2001) estimated the rate of cometabolic dioxin dechlorination in estuarine Passaic River sediments at 3-8 pg of diCDD per gram sediment per year, based on sediment respiration rates, and the ratios of dioxin dechlorination as compared to methane production, which represented the dominant TEAP under which these reactions occurred. 

Blaryls are also commonly prepared by photolysis of aryl halides In the presence of arenes and several examples have appeared during the period of this report. Photolysis of lodothiophenes in the presence of thiophene gives 2.2 -bithienyls and this has been applied to the synthesis of several naturally occuring compounds. For example, irradiation of 2-iodothiophene-2-carbal-dehyde in the presence of 2-bromothiophene gives the bithienyl (153) In 99% yield. This is then converted Into a series of natural products In which the aldehyde and bromo functions of (153) are modified. Similarly. 

The obvious limitation of this reaction so far is in the electrophile as we have suggested naturally electrophilic enones as ideal partners for aryl or vinyl palladium o-complexes. In fact, complexation with palladium makes all alkenes electrophilic and nucleophilic addition can in principle occur to a simple alkene while it and the nucleophile are both bound to the palladium atom. Such reactions are known for aryl halides. Even ethylene itself does satisfactory Heck reactions and its reaction with the bromopyridine 132 is the basis for a large scale process leading to a drug.21... 

As shown in Section 2 diarylethers are also widely occurring structural units in natural products. Despite its serious drawbacks, up to relatively recently, Ullmann s procedure was almost exclusively the method of choice for preparing diarylethers. According to the original methodology, phenols and aryl halides can be coupled to diarylethers in the presence of activated copper powder and potassium carbonate [134] (Scheme 54). 

One of the most versatile approaches to highly functionalized carbazoles is the sequential palladium-catalyzed C-N/C-C coupling for assembly of the central pyrrole moiety. Many total syntheses of naturally occurring carbazole alkaloids are following this route. The initial C-N bond formation by a palladium(0)-cata-lyzed Buchwald-Hartwig amination of aryl halides or triflates 94 with arylamines 31 affords the diarylamines 95 (Scheme 24) [139,140]. Oxidative cyclization of the diarylamines 95 to the carbazoles 32 proceeds via a double C-H bond activation and is achieved in the presence of palladium(ll) compounds. 

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