Double cyclization of O-acylated hydroxyamides generates 1,6-dioxa-3,9-diazaspiro[4.4]nonanes a new class of oxy-oxazolidinones

Abstract

New diazaspirononanes are synthesized employing excess amounts of reagents, whereas using stoichiometric amounts of reagents leads to silyl carbamates.

A Cascade Process of Hydroxamates Renders 1,6-Dioxa-3,9-diazaspiro[4.4]nonane-2,8-diones

“…cyclic compound was isolated. Overall, the proposed mechanism in this work mainly relies on the recently reported mechanism 15 (see previous work in Scheme 4).…”

“…structure analysis of the same compound generated from the double cyclization of (R)-2-(benzylamino)-2-oxo-1phenylethyl (S)-2-[(tert-butoxycarbonyl)(methyl)amino]propanoate ( Figure 1). 15…”

“…From the mechanism point of view, it can be postulated that Boc-protected silyl iminoether 5(i) converts into the corresponding tert-butyldimethylsilyloxy carbonyl derivative 5(ii) upon using 1.0 equivalent each of the reagents as discussed previously. 15 In the presence of an excess amount of the reagents, the silyl carbamate can further proceed to generate spirocyclic orthoamides. Alternatively, loss of the tert-butyldimethylsilyloxy carbonyl group (COOTBS) results in the cyclized products (i.e., 8e and 8h).…”

(R,R/S,S)-9-Benzyl-3-methyl-7-phenyl-1,6-dioxa-3,9-diazaspiro[4.4]nonane-2,8-dione

“…The biological significance of spirocyclic molecules has inspired considerable research towards the discovery of new synthetic routes to such compounds (Rios, 2012). We have recently reported (Nazarian & Forsyth, 2016) the preparation of 1,6-dioxa-3,9-diazaspiro [4,4]nonane-2,8-diones, a new class of spirocyclic othoamide. These were achieved by double cyclization of O-acylated hydroxamides utilizing a modification of an analogous procedure for 2-oxy-1,3-oxazolidin-4-ones (Kamimura et al, 2002(Kamimura et al, , 2003(Kamimura et al, , 2006.…”

“…A search of the Cambridge Structural Database (CSD Version 5.39, August 2018; Groom et al 2016) for the 1,6dioxa-3,9-diazaspiro[4,4]nonane-2,8-dione skeleton yielded hits for three substituted analogues from our previous study (CSD refcodes IAPDIO, IAPDOU, IAPDUA; Nazarian & Forsyth, 2016). Additionally, there was one example of an oxazolidine-4-one ring in a spirocyclic multi-ring natural product analogue (CSD refcode KEMXOR; Oguri et al, 2012) in which the heterocyclic ring has an envelope configuration on the ether oxygen atom, similar to the current structure.…”