Oxidative bridgehead

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

The evidence for this mechanism includes the facts that nitrous oxide is a product (formed by 2 HNO —y H2O + N2O) and that quinuclidine, where the nitrogen is at a bridgehead, and therefore caruiot give elimination, does not react. Tertiary amines have also been converted to nitrosamines with nitric acid in Ac20 and with... 

Selective oxidations are possible for certain bicyclic hydrocarbons.285 Here, the bridgehead position is the preferred site of initial attack because of the order of reactivity of C—H bonds, which is 3° > 2° > 1°. The tertiary alcohols that are the initial oxidation products are not easily further oxidized. The geometry of the bicyclic rings (Bredt s rule) prevents both dehydration of the tertiary bridgehead alcohols and further oxidation to ketones. Therefore, oxidation that begins at a bridgehead position... 

The oxidative addition of hexafluoroacetone to 221 gives 222 (X = CH) in which chloromethane has been eliminated in a ring-closing step to give a product with a bridgehead phosphorus center (Scheme 28). Analogous products 223 were obtained by treatment of 221 (X = N) with hexafluoroacetone (Scheme 29) <2000ZFA412>. The oxidative addition was found to be reversible. 

The structures of these oxidation products were confirmed by X-ray crystallography (Fig. 11). The oxygen atom of 8 connects two bridgehead silicon atoms with a Si-O bond length of 1.683(4) A and a Si-O-Si bond angle of 120.2(4)°. The Si-O bond length is somewhat longer than those of... 

However, when there is a substituent on the bridgehead carbon, the product of the oxidation would be the keto-alcohols (461) and the ketone (462) (Table 20) 157). 

The number of methods available for the synthesis of bicyclic systems containing two fused five-membered rings with one bridgehead nitrogen can be summarized in a few general reactions dehydrative ring closure, oxidative Schiff base cyclization, and base-induced closure (Scheme 3). One-pot reactions involving precursor synthesis followed by cyclization are also known. 

Figure 15. Two-electron oxidation of 1,2-dithiin 20 and 1,4-dithiin 21 with the lH NMR chemical shifts (ppm) of the bridgehead protons.

However, electrooxidation of 1-bromoada-mantane involves the transfer of more than three electrons to afford Af-(1-adamantyl)acetamide. In a comparable study of the oxidation of 2-haloadamantanes and their methyl-substituted analogues [13], it was observed that the products depend upon the identity of the halogen atom as well as the number of bridgehead methyl groups. 

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... 

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

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

The oxidation potential of the carbon-bromine bond is close to that for the bridgehead carbon-hydrogen bond in adamantane. Thus, 2-bromoadamantane in acetonitrile undergoes mainly oxidation at the bridgehead positions, retaining the... 

The proposed catalytic cycle is outlined in Scheme 9.9 [14]. Dimeric complex 23 is cleaved to give the monomeric complex 24 by solvation, substrate binding, or reaction with the nucleophile. Reversible exo-coordination of the substrate is followed by oxidative insertion with retention into a bridgehead C-O bond to give the 7r-aUyl or u-rho-dium aUcoxide complexes 26 or 27. It is likely that the formation of these rhodium] 111) aUcoxide complexes is irreversible due to the release of the ring strain present in the oxabicyclic aUcene substrate. The oxidative cleavage of the C-O bond is proposed to be the enantiodiscriminating step in the catalytic cycle. 

The asymmetric synthesis of (+)-Codeine 432 devised by White and colleagues included a Beckmann rearrangement to introduce the nitrogen atom in the carbocyclic structure (equation 182). Even though two isomeric lactams 430 and 431 were obtained as a result of the rearrangement, the preferential migration of the bridgehead carbon atom produced 430 as the predominant isomer. The synthesis of the non-natural enantiomer of Codeine was completed after oxidation, olefin formation and reduction. 

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