Synthetic Approaches to Spiroaminals

Abstract

The 1‐oxa‐7‐azaspiro[5.5]undecane, 1‐oxa‐6‐azaspiro[4.5]decane, 1‐oxa‐7‐azaspiro[5.4]decane and 1‐oxa‐6‐azaspiro[4.4]nonane ring systems are found as the cores of natural or synthetic products that possess significant biological activities. Because of their potential applications, together with the novelty of their skeletons, these compounds represent challenging targets for chemical synthesis. In this review we summarize the different strategies developed for the synthesis of these spiroaminals.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Facile Construction of Oxa‐Aza Spirobicycles via a Tandem Carbon‐Hydrogen Bond Oxidation

“…For example, the natural products marineosins A and B,1 azaspiracid,2 tomatidine,3 sanglifehrin A,4 manzamine X,5 stemotinine and isostemotinine alkaloids6 have an oxa‐aza spirobicyclic unit as their core structure. These important skeletons have attracted the attention of a number of synthetic research groups, and many synthetic methods have been documented 7. Cyclization of hemiaminals8 or hemiketals9 (path a, Scheme ) and bicyclization of the functionalized ketone derivatives10 (path b, Scheme ) are the classical and commonly used approaches to oxa‐aza spirobicyclic systems.…”

Ruthenium-Catalyzed Intramolecular Double Hydrofunctionalization of Alkynes. Synthesis of Spirocyclic Hemiaminal Ethers and Their Lewis Acid-Mediated Cleavage/Nucleophilic Addition

“…Spirocyclic hemiaminal ethers, hereafter referred to as spiroaminals, are compounds having an oxa-aza spirobicyclic structural motif embedded in a variety of biologically active natural products and are also of interest in medicinal chemistry as representing a uniquely rigid three-dimensional scaffold with diverse appendages . Compared with the oxa–oxa spirobicyclic counterpart spiroacetals, much less attention has been paid to synthetic methods for spiroaminals . Perhaps, the most common approach is dehydrative cyclization of keto amino alcohols .…”

Catalyst-free formal [4+1]/[4+2] cyclization cascade sequence of isocyanides with two molecules of acylketene formed in situ from thermal-induced Wolff rearrangement of 2-diazo-1,3-diketones

“…1). As a result, not surprisingly, many efficient synthetic strategies leading to functionalized O,Ospiroketals [14][15][16][17][18][19][20][21][22][23] and N,O-spirohemiaminals [24][25][26][27] have been developed and well-studied. However, to the best of our knowledge, protocols toward compounds with a X,X,Y-spiro structure such as O,O,N-spiro skeleton remain underdeveloped.…”