Atroposelective reactions synthesis

Removal of the amide function is much easier if the reaction is intramolecular, and —CONEt2 amides (sometimes even —CONPr-i2 amides) may be converted to lactones, lactams and other heterocycles in this way . Addition of an aldehyde or ketone as an electrophile generates a hydroxyl group (in some cases, atroposelectively, as it happens —though this is usually irrelevant to the stereochemistry of the product) which cyclizes to give a lactone via a benzylic cation in acid. This reaction has found wide use in the synthesis of polycyclic aromatics, particularly alkaloids. 

An efficient atropo-enantioselective total synthesis of the axially chiral bicoumarin (+)-isokotanin was accomplished by J. Bringmann and co-workers.The key steps in this synthetic approach were the formation of a configurationally stable seven-membered biaryl lactone by the Cannizzaro reaction of the corresponding biaryl dialdehyde followed by a kinetic resolution by atroposelective ring cleavage. 

As part of their investigations towards the synthesis of the cytotoxic marine natural product diazonamide A, Feldman et al. discovered a noteworthy atroposelective macrolactonisation reaction. Thus, the ring closure of the configurationally flexible model bisindole depicted in Scheme 5.29 afforded the corresponding lactone as a single isomer. The bulk of the NB0C2 group was... 

Narbonne et al. developed a one-pot catalytic method for the synthesis of dibenzo[c,e]azepines and their imine analogues in 2014. ° The reaction was catalyzed by a joint palladium-norbornene organometallic catalyst. The complete diastereoselectivity observed originates from a chelated Pd(iv) complex via atroposelective atyl-atyl coupling. The desired dibenzo[c,e]aze-pines were isolated in good yields (Scheme 4.23). 

The versatility of the Meyers reaction for the construction of the dibenzocyclooctadiene backbone is amply documented (Fig. 8.2). In particular, lignans (-)-interiotherin A (17) [21], (-)-schizandrin (18), (-)-isoschizandrin (19) [22], and (-)-gomisin E (20) [21] were prepared by this method. The synthetic utility of the Meyers reaction to create the axially chiral biaryl skeletal framework was further displayed by the atroposelective syntheses of natural naphthylisoquinoline alkaloids including (-)-O-methylancistrocladine (21) [23] and (-)-0-methylhamatine (22) [24], among others [25, 26], and by the synthesis of enantiomericaUy pure C -symmetric biphenyl ligand 23 and binaphthyl porphyrin 24 (Fig. 8.3), which have been used as intermediates for the preparation of chiral catalysts for asymmetric reduction and epoxidation [27, 28]. 

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