Heterocycles preparation

Scheme 74. Palladium-catalyzed further transformations of heterocycles prepared from methyl 2-chloro-2-cyclopropylideneacetate (1-Me) [53,73]...

Several review articles have appeared covering the synthesis of heterocycles on insoluble supports for the production of compound libraries for drug discovery [1-4]. In this chapter, these syntheses have been organized according to the type of heterocycle prepared. 

Fused ring heterocycles, prepared by cyclization of substrates with a tethered nitrogen nucleophile, have been used in the synthesis of amino sugars and aminocyclitols. The examples shown in Table 28 make use of imidate-type functionality (equation 101) to insure nucleophilic attack by nitrogen. The bro-mocyclization of N,W-dialkylaminomethyl ethers of 2-cyclohexen-l-ol to form bicyclic oxazolidine derivatives has been reported also.228b... 

Fig. 4. Five-membered azole heterocycles prepared by cyclative cleavage.

See Dinitrogen pentaoxide Strained ring heterocycles Preparative hazard... 

Nitrogen heterocycles, preparation from aziridinium salts ... 

The ixeparatirai of many unsaturated heterocyclic compounds can be achieved via rDA processes. The vast majority of these compounds are either oxygen or nitrogen containing heterocyclics, preparation of which is most often accomplished by the expulsirai of an ethylene or a butadiene moiety. a-Methylene-oxetane (175a) and p-methyleneoxetane (175b) are obtained by a rDA process from the anthracene cycloadducts. 

The synthesis of heterocycles via rDA processes includes the preparation of heterocycles with two different heteroatoms. Furo[3,4-c]pyridine (218), a previously unknown polyheterocyclic, has beat achieved by FVP of adduct (217) (equation 98). The heteropentalene Aieno[3,4-6]fuian (220) has been synthesized by a reaction pathway based upon rDA formation of polyheterocycle (219) (equation 99). Other heterocycles prepared via rDA reactions that contain two differoit heteroatoms include 6H-l,3-oxazin-6-one (221) and 3-arylisoxazoles (222). ... 

The potential of this approach for heterocycle preparation has by far not been exhausted, as is the case for systems containing other or more heteroatoms within the frame executing the Cope rearrangement. ... 

Heteroannulation of alkynes is an efficient method for the preparation of complex heterocycles. Preparation of the preannulation substrate is often accomplished via Sonogashira coupling. Indeed, this protocol has been utilized effectively for the preparation of quinazolinones [107] and benzothioazoles [108]. The reactions have been carried out on substituted iodopyrimidines to provide the desired complex heterocycles. 

Other heterocycles prepared using iminophosphoranes include novel py-rimidinone and quinazoline derivatives, obtained from in situ aza-Wittig reactions of N aryl-iV-(triphenylphosphoranylidene)carboxidamides (114) and ketenes, and pyridothienopyridazines and pyrimidothienopyridazines, accessed from aza-Wittig/electrocyclic-ring closure reactions between phos-phoranes (115) and (116) and heterocumulenes. ... 

Lown and Matsumoto,7 in a comprehensive study on the reactions of diphenylcyclopropenone (11) with nitrogen heterocycles, prepared 6-hydroxy-2,7,8-triphenylpyrrolo[l,2-a]pyrimidine (13) by allowing 4-phenylpyrimidine (12) to react with 11 [Eq. (2)1. This synthesis can also be viewed as a 2,3-dipolar cycloaddition reaction in which 11 serves as a very reactive 1,3-dipole and the 4-phenylpyrimidine (12) is a dipolaro-phile. Note that in both of these syntheses the pyrrole portion of the resulting bicyclic system is completely substituted. 

Among the condensed heterocycles prepared by condensation reactions of 10 are many pyridine derivatives. So Knoevenagel condensation of two mol 10 with 19 gave 73. ... 

FIGURE 9.9 Examples of perfluorinated heterocycles prepared using C0F3 as fluorinating... 

Triazoles are obtained via 1,3-dipolar cycloadditions between azides and al-kynes, and they are probably the most common nitrogen heterocycles prepared on solid supports via 1,3-dipolar cycloaddition. A wide variety of 1,2,3-triazoles have been prepared on solid supports, with an alkyne or azide attached to the resin. In addition, various linkers have been studied. Alkyne-functionalized alcohol was attached to the MeOPEG resin with an oxalyl chloride linkage (Scheme 11.23). Cycloaddition of alkynes with carbohydrate-derived azides gave resin-bound 1,2,3-triazoles, and reductive cleavage with sodium borohydride released the products as primary alcohols. 

Allylsilanes have been used in heterocycle preparation, and in the synthesis of the Prelog-Ljerassi lactone, (+)-mosembrine, such hydroxylactams as (+)-isoretronecanol and ( )-epilupinine, while oxidation to give -silyl enones is used in the preparation of... 

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