A means for stereocontrolled introduction of the C-2 oxygen substituent in functionalized cis-tricyclo[9.3.1.03,8]pentadecanones related to taxol
TL;DR: In this article, anionic oxy-Cope rearrangement of exo-norbornanol precursors that have been obtained by convergent coupling of two functionalized reaction partners was investigated.
Abstract: Several optically pure cis-tricyclo[9.3.1.0 3,8 ]pentadecanones have been prepared via anionic oxy-Cope rearrangement of exo-norbornanol precursors that have been obtained by convergent coupling of two functionalized reaction partners. The sigmatropic rearrangement is shown to proceed with exceptionally good stereochemical transmission because of universal adherence to the same endochair transition state. The atropisomeric aspects of this pivotal transformation are addressed. Also investigated was the proclivity of the products to undergo transannular hemiketal formation following osmylation of the bridgehead double bond. As matters turn out, the operation or nonoperation of this intramolecular addition to the C-9 carbonyl group is amenable to control merely by adjusting properly the stereochemistry of a single pendant substituent
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TL;DR: DFT calculations at the B3 LYP/6-311G** level give an insight into why 1 and 2 adopt dramatically different structures from their previously reported, "open-dimeric", lithium counterpart.
Abstract: Two heavy alkali-metal salts of the sterically demanding amine, 2,2,6,6-tetramethylpiperidine (TMPH), have been prepared using different methodologies. Complex 1, [{(tmeda)Na(tmp)}2] (TMEDA=N,N, N,N-tetramethylethylenediamine), can be synthesized by a deprotonative route. This is achieved by reacting butylsodium with TMPH in the presence of excess TMEDA in hexane. The potassium congener [{(tmeda)K(tmp)}2] (2), can be prepared by treating KTMP (made using a metathesis reaction between LiTMP and potassium tert-butoxide) with an excess of TMEDA in hexane. In the solid state, 1 and 2 are essentially isostructural. They are discretely dimeric and their framework consists of a four-membered M-N-M-N ring (M=Na or K, N=TMP). Due to the high steric demand of the TMP ligand, the TMEDA molecules bind to the metal centers in an asymmetric manner. In 2, each of the coordination spheres of the metals is completed by an agostic KCH3(TMP) interaction. DFT calculations at the B3 LYP/6-311G** level give an insight into why 1 and 2 adopt dramatically different structures from their previously reported, open-dimeric, lithium counterpart. The theoretical work also focuses on the TMEDA-free parent amide complexes and reveals that the energy difference for the formation of [{M(tmp)}x] (in which, M=Li or Na, x=3 or 4; and M=K, x=2, 3 or 4) are small. (Abstract copied from: http://www3.interscience.wiley.com/journal/120840676/abstract)
45 citations
28 citations
TL;DR: In this article, an asymmetric synthesis of the oxetane-containing norbornanone and its coupling to trans-1-propenyllithium to give 24 are reported, in tandem with the preparation of the related alcohols 28 and 30.
Abstract: 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 (0 °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.
22 citations
TL;DR: In this paper, the Meyer-Schuster rearrangement is employed to form the highly sterically hindered taxol 1,2-bond, which is obtained by oxidative cyclization of homogeranic acid with mercuric triflate.
17 citations