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†
Giorgio Giorgi,Pilar López-Alvarado,J. Carlos Menéndez
Organic & Biomolecular Chemistry Pub Date : 05/08/2012 00:00:00 , DOI:10.1039/C2OB25274K
Abstract

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.

Graphical abstract: 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