Bridgehead bromide

The apocamphyl structure is particularly rigid, and bridgehead caibocationa become accessible in more flexible structures. The relative solvolysis rates of the bridgehead bromides 1-bromoadamantane, l-bromobicyclo[2.2.2]octane, and l-bromobicyclo[2.2,l]-... 

Preliminary results confirm the expected utility of direct ionic substitution reations for the preparation of derivatives of diamantane. In refluxing bromine, diamantane gives 1-bromodiamantane (74) 26S> as well as a variety of disubstituted bridgehead bromides (Eq. (64)) 266 If, on the other hand, the reaction is carried out in the presence of AlBr3, significant amounts of 4,9-dibromodiamantane, 77, are also observed (Eq. (65) 265l Treatment of this dibromide with one equivalent of trialkyltin hydride yields the 4-mono-substituted diamantane, 78. 

G.A. Kraus and co-workers utilized the quasi-Favorskii rearrangement of a bicyclic bridgehead bromide as the key step in their formal total synthesis of ep/-modhephene. The required bicyclo[3.3.1]nonenone bridgehead bromide precursor was prepared by a Robinson annulation reaction between 3-bromo-2-oxocyclohexanecarboxylate and MVK. Upon treatment with lithiated dimethyl methylphosphonate, the bicyclic bromo ketone underwent a facile quasi-Favorskii rearrangement to afford the key intermediate bicyclo[3.3.0]octane derivative. 

Reduction of bridgehead bromides. Bridgehead bromides are reduced to the hydrocarbons in 90-1007o yields by this hydride with irradiation with ultraviolet light. Yields are lower in the absence of irradiation. This photochemical process is not as effective with bridgehead chlorides. 

Irradiation of bridgehead bromides and iodides (RX) in a variety of solvents (SH) results in the formation predominantly of the nucleophilic substitution products (RS) as well as some hydrocarbon (RH), particularly with the bromides. Both radical and heterolytic cleavage of the photoexcited RX molecules are encompassed within the mechanisms discussed. The systems studied include 1-norbornyl, 1-norbornylmethyl, and 1- and 2-adamantyl bromides and iodides. Electrochemical and metal-ammonia reduction of 1,4-dihalogenonorbornanes yields mainly nor-bornane (and not the required [2,2,l]propellane) and some l,r-bisnorbornane. ... 

The apocamphyl case is an extreme one, and bridgehead carbonium ions in other systems are more accessible. Inclusion of more atoms in the bridge gives a more flexible molecule and allows carbonium ion formation to proceed with a somewhat lower activation energy. Thus, the relative solvolysis rates of the bridgehead bromides 1-bromoadamantane, l-bromobicyclo[2.2.2]octane, and 1-bromobicyclo[2.2.1]heptane in 80% ethanol at 25°C are 1,10", and Under the same conditions, the rate of solvolysis of tert-butyl bromide is 1000 times that of 1-bromoadamantane. The 1-adamantyl cation is sufficiently stable to be generated in antimony pentafluoride in concentrations sufficient for observation by NMR. ... 

Table II. Reaction of Bridgehead Bromides with Sodium Naphthalene...

Reaction of (265) with trimethyltinlithium gives a 30% yield of (266) with retention of configuration, whereas (267) gave a 60 % yield of (266) with inversion. In addition a number of bridgehead bromides react to give bridgehead trimethylstannanes. The results are rationalized in terms of nucleophilic attack by tin on either carbon in a conventional 5 2 process or on bromine (when present) to give a cyclohexyl-lithium which yields product in a fast reaction with Me,SnBr. 

Adamantylamine is prepared from the corresponding alcohol or bromide by bridgehead cation generation in the presence of acetonitrile (49). Selective hydrolysis of the resultant acetamide to the rigid cycloahphatic amine by acid or base is difficult. 

The synthesis of a bridgehead sulfonium salt analogue 59, of the naturally occurring glycosidase inhibitor castanospermine, proceeded by a multistep procedure starting from 5-thio-d-glucopyranose pentaacetate <2000JA10769>. The desired bicyclic sulfonium salt 57 could not be obtained from the key bromide precursor... 

In 2003, Williams and Mander reported a method designed to access the hetisine alkaloids (Scheme 1.3) [27]. This approach, based upon a previously disclosed strategy by Shimizu et al. [28], relied on arylation of a bridgehead carbon via a carbocation intermediate in the key step. Beginning with (1-keto ester 46, double Mannich reaction provided piperidine 47. Following a straightforward sequence, piperidine 47 was transformed to the pivotal bromide intermediate 48. In the key step, bromide 48 was treated with silver (I) 2,4,6-trinitrobenzenesulfonate in nitro-methane (optimized conditions) to provide 49 as the most advanced intermediate of the study, in 54 % yield. 

Bridgehead Fluorides from the Corresponding Bromides General Procedure 90... 

If /-butyl chloride solvolyzes by a mechanism like that depicted in Figure 5.6c, without any significant nucleophilic assistance at the transition state, the sensitivity to changes of solvent nucleophilicity ought to be the same as for the bridgehead systems. This is the result found when the reactions of /-butyl chloride (Equation 5.19) and adamantyl bromide (Equation 5.20) were compared.96 The... 

In the absence of AlBr3, the kinetic product is the 1-bromide, 74. Further bromination, if it occurs, takes place at the most remote bridgehead positions available to give 75 and 76. When AlBr3 is present in the reaction mixture, characteristically decreased selectivity is observed (see also Section II.B). Bromination at the 4-position is able to compete effectively and 77 is obtained as one of the bromination products. 

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