Convergent approach

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

The convergent approach comprises, among other reaction steps, a regio-specific intermolecular benzannulation reaction between the alkyne 88 and the chromium carbene complex 89 for AB ring construction (Scheme 43). It is noteworthy that the regioselectivity of this reaction is attributed to the bulky TBDMS ether in the alkyne a-substituent, that dictates the incorporation of the large substituent ortho to the phenol. Another curiosity is the fact that the reaction failed to provide 90 in the absence of acetic anhydride. 

The convergent approach overcomes these problems to an extent, but still gives more or less imperfect structures depending on the purity of the reagents and the efficiency of the reactions used. 

Scheme 15. Rapid convergent approach of the synthesis of first-generation ruthenium-acety-...

The synthesis of both haliclamines A (64) and B (65) has been achieved (Scheme 6). The first synthesis of both 64 and 65 [35,36] was a convergent approach starting from the monoprotection and functional group interconversions (FGls) of 1,4-butanediol (66) to the monoprotected iodide (67), which... 

Frdchet et al. reported the synthesis of a unimolecular micelle (Fig. 6) generated by a convergent approach starting with 3,5-dihydroxybenzyl alcohol, as the key branched monomer unit [65]. Fourth generation dendrimer 15 with 32 carboxylic acid moieties on the periphery was synthesized and its correspond-... 

There is a plethora of examples representing dendrimers with metal-binding sites on the periphery. Polycarboxylates were the simplest, early examples [179], although dendrimers possessing more complicated ligand complexing centers have invariably been built via a convergent approach. 

The subsequent deprotection of the hemiacetal concluded the synthesis of 1. We also successfully used this convergent approach to synthesize nakiterpiosinone (2) and 6,20,25-< /E-nakiterpiosiii (49). 

C. J. Hawker and J. M. J. Frechet, Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules, J. Am. Chem. Soc., 112 (1990) 7638-7647. 

H. Ihre, A. Hult, J. M. J. Frechet, and I. Gitsov, Double-stage convergent approach for the synthesis of functionalized dendritic aliphatic polyesters based on 2,2-bis(hydroxymethyl)propionic acid, Macromolecules, 31 (1998) 4061 1068. 

A nice and convergent approach to both compounds makes use of RCM to form the 5-membered building block 71, which mimics the carbohydrate part of the nucleosides. The necessary diene precursor 69 is readily assembled via Evans aldol chemistry. RCM then affords the ring in almost quantitative yield (69->70), leaving the chiral centers and the free hydroxyl group intact. Removal of the chiral auxiliary by reductive cleavage, attachment of the base by means of jt-allylpalladium chemistry, and a final deprotection step complete these highly efficient syntheses [46]. 

The first total synthesis of (-)-reserpine (109) was published in 1956 and 1958 by Woodward and co-workers (233, 234). Although this ingenious work has already been reviewed in The Alkaloids (3), it is worthwhile to present the reaction sequence to recapitulate this convergent approach. 

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