A one-pot sequence for the efficient synthesis of highly functionalized macrocarbocycles or bridged 2,8-dioxabicyclo[3.2.1]octanes from 1-nitrobicyclic compounds.
The reaction of 1-nitrobicyclo[n.3.1]alkane-(6 + n)ones with sodium borohydride followed by acidic workup led to ring opening via a one-pot sequence comprising the retro-Dieckmann-type opening of the α-nitroketone structural fragment, followed by aldehyde reduction and a final Nef reaction, leading to highly functionalized 12 to 14-membered carbocyclic ketones bearing three stereocenters, which are adjacent in some of the compounds. The reactions starting from 1-nitrobicyclo[9.3.1]pentadecan-15-ones could be adjusted to give macrocyclic 2,8-dioxabicyclo[3.2.1]octanes containing an additional bridge by diastereoselective formation of a third ring and a fourth stereocenter through acid-promoted intramolecular ketal formation. This is a very interesting ring system related to the core of the zaragozic acid family of natural products.
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Giorgio
G
Giorgi
Pilar
P
López-Alvarado
J Carlos
JC
Menéndez
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry; D009795:Octanes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D002264:Carboxylic Acids; D007659:Ketones; D047028:Macrocyclic Compounds; D009574:Nitro Compounds; D009795:Octanes