Bridgehead Heterocycles

Another important example of oxidative cyclization leading to bridgehead heterocyclic compound is the conversion of indole derivative 211 

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I.3.3.I. Reaction of 2-Lithiomethylpyridine 88.11, 1-Lithiomethylisoquinoline 85.12,2-Lithiomethylthiozole 85.14/thiazolidine 85.15,3-Aminopyrazole 85.17 with 6 A New General Method for Bridgehead Heterocycles... 

With a-A3-iodanyl ketone precursors. Exposure of (2-acetoxyvinyl)phenyl-A3-iodanes 369 to 2-imidazolidinethione and triethylamine in methanol produced the bridgehead heterocycle 370 of type 5,6-dihydro-imidazo[2,l-3]thiazoles (Equation 166) <2003JOC7887>. 

Several 2-thiazolyl- (194) and 2-benzothiazolyl- (197) hydrazones of aromatic aldehydes undergo oxidative intramolecular cyclization to form 1,2,4-triazolo-bridgehead heterocycles 195 (95SC3363) (Scheme 53) and 198 [93JCR(S)244] (Scheme 54), respectively. In the case of 194, l-acetoxy,l-(4-aryl-2-thiazolyl)-2-aroylhydrazines (196) are formed as minor products (Scheme 53). 

A general scheme, which constructs the thiazolo variety of various bridgehead heterocycles, is basically an extension of HTIB-mediated modification of Hantzsch thiazole synthesis (Scheme 51). Thus, synthesis of 3-substituted-5,6-dihydro-4//-imidazo[2,l-b]thiazoles 202 has been achieved by the treatment of a-tosyloxyacetophenones (generated by the oxidation of 51 with HTIB) with ethylenethiourea [92JCS(P1)707], The method is successfully extended to synthesize 4,5,6,7-tetrahydrothiazolo[3,2-a]pyrimidines 203... 

Similarly, intramolecular participation of nitrogen in the oxidation of carbamates 281 affords bridgehead heterocycle 282 in high yield. 

A comprehensive review of the entire field of N-bridgehead heterocyclic compounds given by W. L. Mosby covers the literature until 1958 (61 Mil). Heterocycles of this type have since found interest in chemistry and... 

A silicon bridgehead heterocycle (65), in effect a formal adduct of dimethyldisilyne, is formed as shown in Scheme 12 <86JA424l>. Its structure was confirmed by x-ray crystallography. Formation of the adduct is thought to proceed via the interesting, but undetected, disila-dibenzobarrelene (66), containing an Si=Si double bond. 

Xi and co-workers reported a eopper-catalyzed domino N-H/C-H bond activation for the synthesis of nitrogen-bridgehead heterocycles by using azoles and l,4-dihalo-l,3-dienes as substrates. The reaetion exhibits good regioselectivity when unsymmetrieal l,4-dihalo-l,3-diene was employed. A variety of azolopyridine derivatives were produeed in good yields (Scheme 3.52). 

Since diazaquinones are among the most powerful dienophiles, they undergo [4+2] cycloaddition (Diels-Alder) reactions with a great variety of dienes to give various heterocyclic systems accessible with difficulty by other methods. Diazaquinone reacts with butadiene and substituted butadienes, carbocyclic and heterocyclic dienes, 1-vinylcycloalkenes, polyaromatic compounds and vinylaromatic compounds to afford bicyclic and polycyclic bridgehead diaza systems, including diazasteroids (Scheme 56). 

P=C moiety in heterophospholes undergoes cycloaddition reactions with a variety of dienes and dipoles to afford a range of new heterocycles having bridgehead phosphorus atom [2, 4, 97, 98]. Previously, the reactivity of diazaphospholes towards cycloaddition reactions has been investigated to a limited extent [98],... 

The infrared (IR) spectra of these compounds were mostly studied in the solid state which showed all the basic peaks characteristic of various functionalities attached to such bicyclic heterocycles with bridgehead nitrogen atoms. The difference in the frequency of carbonyl and carbon nitrogen double bond in tautomers of compound 18 (R = H) has been discussed previously in CHEC-II(1996) <1996CHEC-II(8)713>. 

Batten et al. <2004AXCm311> have reported an Fe(n) complex using a tris(heterocycle)tripod-type ligand with phosphorus at the bridgehead. Compound 23 was fully characterized using X-ray crystallography. 

The reaction of triallylborane with silicon triyne 123 is interesting. A113B attacks both internal and external triple bonds giving rise to silole 124 and two heterocycles with bridgehead boron 125 and 126 in a 1 3 3 ratio as a result of competitive sequential reactions (Scheme 52). When 1,1-allylboration of the internal C C bond followed by intramolecular 1,1-vinyIboration takes place, the silole 124 is formed, while in another case 1,1-allylboration followed by a series of intramolecular 1,2-allylboration reactions leads to boron derivatives 125 and 126 <2002JOM(657)146>. 

Heteroaromatic Annulation with Cyclic Azaallyl Anions Synthesis of Bridgehead Nitrogen Heterocycles... 

The azaallyl anions 85.11-85.17 derived from cyclic nitrogen heterocycles generally react with 6 to afford the corresponding bridgehead nitrogen heterocycles. Some of the examples studied by our group are described below. 

Linke, S., Kurz,., Lipinski, D., and Gau, W., Annealation reactions of N-heterocycles to condensed pyridones with bridgehead nitrogen, Ann. Chem., 542, 1980. 

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