Synthesis and acidolysis of 3-endo-azidomethyl- and 3-endo-azidobicyclo[3.3.1]non-6-enes. A novel synthesis of 4-azahomoadamant-4-enes

Abstract

The acidolysis of 3-endo-azidomethylbicyclo[3.3.1 lnon-6-ene (3) with methanesulphonic acid gave 4-azahomoadamant-4-ene (5) which was also produced from 3-endohydroxymethylbicyclo[3.3.1] non-6-ene (6) on treatment with NaN,-MeS0,H.The formation of (5) was rationalized by a x route cyclization followed by acidolytic ring expansion of intermediate azides on the basis of acidolysis of dideuterioderivatives. The above route was extended to synthesis of 2,2-(1 6) and 7,7-dimethyl-4-azahomoadamant-4-enes (1 7). The acidolysis of 3-endo-azidobicyclo[3.3.1] non-6-ene ( 2 3 ) gave 2-aza-adamantan-anti-4-01 (26) via a x-N+ type cyclization.Organic azides are well-known as excellent synthetic starting materials for various nitrogen-containing organic molecules, although, studies utilizing azide functionalization of carbocycles, particularly, bi-and tri-cycles seem, as yet, to be underdeveloped.2 We have therefore been pursuing attractive synthetic routes to aza-adamantane and related derivatives by utilizing azide functionalization of bi-and tri-carbocycles in order to study their biological proper tie^.^ Previously, we reported convenient and efficient synthesis of 4-azahomoadamant-4-ene and its 5-substituted derivatives by acidolysis and/or photolysis of 2-a~idoadamantanes.~ Here, we report the synthesis of 3-endo-azidomethyl-and -azidobicyclo[3.3.1]non-6-enes and their acidolysis behaviour, the latter providing novel routes to 4-azahomoadamant-4-enes and 4-hydroxy-2aza-adamant ane, respectively .* Eu(fod)3 = tris-(

Oxamidation of Unsaturated O-Alkyl Hydroxamates: Synthesis of the Madangamine Diazatricylic (ABC Rings) Skeleton

“…Employing our previously reported conditions for the oxamidation of unsaturated O -alkyl hydroxamates, sequential treatment of 20 with trifluoroacetic acid (1.0 equiv) and phenyliodine­(III) bis­(trifluoroacetate) (PIFA) (1.2 equiv) in CH 2 Cl 2 , provided 18 in high yield after in situ cleavage of trifluoroacetate ester 26 with methanolic ammonia (Scheme ). Compound 18 was isolated as a single diastereomer, which arises from regioselective ring opening at C-3; no trace of the 2-azabicyclo[3.2.2]­nonan-7-ol arising from distal opening was detected. Importantly, this process is amenable to scale up and has been conducted on multigram scales without decrease in efficiency.…”