217820-03-6Relevant academic research and scientific papers
Stereochemical models for the enantiocontrolled construction of fully functionalized C rings via intramolecular aldolization in advanced precursors to paclitaxel
Paquette, Leo A.,Zeng, Qingbei,Tsui, Hon-Chung,Johnston, Jeffrey N.
, p. 8491 - 8509 (2007/10/03)
Six transition-state models for intramolecular aldol C-ring annulation in suitably substituted bicyclo-[6.2.1]undecanones have been defined. The first consideration is the inherent conformational flexibility of the nine- membered ketonic ring which does not limit effective deprotonation to a single C-8 epimer. When the oxygen substituents at C-4 and C-5 are not covalently linked, the configuration at C-5 defines the stereochemical course of the ring closure, with only the β series being amenable to the proper elaboration of paclitaxel. When C-4 and C-5 are incorporated into a 1,3- dioxane ring instead, the principal stereocontrol element is translocated into the aryl-substituted carbon of the cyclic acetal. To the extent that the Ar group remains equatorially disposed, then proper aldolization will materialize in only one of the four possible diastereomers. Experimental tests that are provided for three of the models are shown to conform to expectations. This analysis of the origin of stereoselectivity has, for the first time, defined the scope and limitations associated with C-ring closure by means of the aldol protocol.
Reversible charge-accelerated oxy-cope rearrangements
Tsui, Hon-Chung,Paquette, Leo A.
, p. 9968 - 9977 (2007/10/03)
An asymmetric synthesis of the oxetane-containing norbornanone 23 and its coupling to trans-1-propenyllithium to give 24 are reported, in tandem with the preparation of the related alcohols 28 and 30. All three divinyl carbinols undergo anionic oxy-Cope rearrangement very rapidly at low temperature. Quenching of 24-K+ and 28-K+ under these conditions with water or various aqueous salt solutions results in protonation of the alkoxides. If these reaction mixtures are poured instead onto cold (O °C) silica gel, their sigmatropically related ketones are isolated in very good yield. Whereas the 24-K+?25-K+ equilibrium pair is not reactive to molecular oxygen, 30-K+ is directly converted into an α-hydroperoxy ketone under comparable conditions. These and additional observations are rationalized in the context of atropisomerism involving conversion of oxygen- up enolates, formed reversibly under kinetically controlled conditions, into their thermodynamically favored, more reactive oxygen-down conformers.
