Cycloheptane- 1-carboxylate

The key step in a reported total synthesis of d/-serratenediol involves the acid-catalysed, biogenetic-like cyclization of a polyene with partial structure (23), which gives a mixture of cycloheptanes (24) and (25). When treated with concentrated sulphuric acid and formic acid, (- -)-3,7-dimethylocta-1,6-diene gave 1,4,4-trimethyl-cycloheptane-1-carboxylic acid which was isolated as its methyl ester. 

There are a handful of examples where amino acids with ring sizes of seven members and larger have been prepared using the carboxyl refunctionalization reaction just shown. Reaction of anhydride 7.29H with ammonia, for example, gave amide-acid 7.30. Hofmann rearrangementl of the amide led to cfs-2-aminocyclo-heptane-1-carboxylic acid, 731. An alternative synthesis conjugate addition of ammonia to cycloheptenecarboxylic acid, 7.32. This reaction gave rra/is-2-amino-cycloheptane-1-carboxylic acid, 7.33. 

Alkylcyclohexanes, cycloheptane, and cyclooctane were also transformed into the esters of the corresponding tertiary cyclohexanecarboxylic acids in the presence of the superelectrophile CBr4—2AlBr3 in good yields.314 315 Such organic superacids generated from polyhalomethanes with aluminum halides are capable of promoting the selective and effective carboxylation of linear alkanes (propane, butane) and adamantane as well.316... 

Several cycloheptane derivatives have been prepared using intramolecular Friedel-Crafts reactions including the tetracyclic ketone (26) and double dibenzotropones , e.g. Acid-catalysed cyclizations of (o-(l-indanyl)-carboxylic acids (28 n = 3... 

The crown catalyzed reaction of potassium superoxide in dry benzene with a-keto-, a-hydroxy-, and a-haloketones, esters and carboxylic acids yields carboxylic acids as formulated in equation 8.9 [12]. The observation that 1-hydroxy-1-carboxy-cycloheptane and a-cyclohexylmandelic acid fail to react under conditions which convert related substrates to acids suggests that a hydrogen alpha to the reactive site is a requisite (see Table 8.5). 

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