Chiral [2.2]paracyclophanes—III. The preparation of unique homochiral amino-acids derived from [2.2]paracyclophane

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

“…The nitration of [2.2]paracyclophane (1) is rarely a clean reaction [55][56][57][58][59][60], and the side-products are believed to include overnitration, as a mixture of regioisomers, as well as the products of oxidation and polymerization. Extensive optimization led us to a set of conditions that routinely provided 4-nitro[2.2]paracyclophane (4) in good yields regardless of the scale of reaction (nitration has been performed on scales ranging from 0.5 g to 30 g).…”

“…For the most part, we have avoided nitration. The literature is full of many different procedures, and the results can be unpre-dictable [55][56][57][58][59][60]. Yet nitration obviously presents one of the most direct routes to 4-amino [2.2]paracyclophanes so we returned to this venerable reaction.…”

The synthesis of substituted amino[2.2]paracyclophanes

“…The ester was first synthesised by the nitration of the ester 12 followed by The yield of the nitration was 15%. 13,53 Pelter later improved the yield by pseudogem-bromination of an oxazoline followed by halogen-metal exchange, reaction with carbon dioxide, Curtius rearrangement and hydrolysis of the oxazoline. The route was 8 steps from 4-bromo [2.2]paracyclophane and gave the amino acid in 36% yield.…”

“…1 H NMR (500 MHz, CDCl3 J = 7.9 Hz), 6.23 (2H, d, J = 7.7 Hz), 5.51 (2H, s), 3.19 (2H, ddd, J = 12.4, 9.7, 1.6 Hz), 3.05 (2H, ddd, J = 15.6, 9.9, 5.9 Hz), 2.91 (2H, ddd, J = 12.7, 10.8, 1.9 Hz), 2.69 (2H, ddd, J = 16.4, 10.7, 5.7 Hz). 13 'One-pot' oxidation-rearrangement methodology [2.2]Paracyclophane-4-carbaldehyde oxime (11). 58 A mixture of hydroxylamine hydrochloride (0.208 g, 3 mmol, 3.0 eq.)…”

“…While moderate to high yields have been reported these require very precise reaction times and conditions. 8,12,13 More common routes to aminoparacyclophanes include the Curtius rearrangement of the appropriate carboxylic acid 9,14,[15][16][17][18] or the electrophilic amination of bromoparacyclophanes. Advantages of the former strategy include facile resolution of the acid 12,19 and the ability of acids to direct functionalisation of paracyclophanes.…”