Investigation of the Chemo‐ and Stereoselectivity of the Ketene‐Claisen Rearrangement

Abstract

A novel type of ketene-Claisen rearrangement in which the precursor of the rearrangement is generated in situ by reaction of optically active allyl thioethers with dichloroketene is described. A characteristic feature of this rearrangement is the excellent chemoselectivity in favor of allyl thioethers vs. allyl ethers, i.e., exclusive chirality transfer of the allylic sulfur moiety is observed with 12, 13, and 25-27. The cyclic, optically active allyl thioethers (+ )-(R)-4 and (-)-(S)-4 and the open-chain allyl thioethers 11-13 rearrange with in sifu generated dichloroketene to the optically active thioesters ( -)-(S)-28, (+)-(R)-ZS, and 31-33, respectively. A chirality-transfer of > 99% in the cyclic cases (+)-(R)-4 and (-)-(S)-4, and 96-98% in the open-chain cases 11-13 is observed. Furthermore, the dichloroketene-Cluisen rearrangement is characterized by a high asymmetric 1,2-induction. The chiral allylic sulfides 25-27 give the optically active thioesters 36-38 with a 1,2-induction > 99% as determined by NMR-shift experiments.

Synthesis of Caged Nucleosides with Photoremovable Protecting Groups Linked to Intramolecular Antennae

“…The Heck coupling product 8 was also prepared from the silyl-protected alcohol 15, made from 14, employing the same conditions as for the unprotected form 10 [26] [27]. Deblocking of the OH group of 15 with Bu 4 NF in THF [26] gave the alcohol 8 in an overall yield of 42% from 10. The caged thymidine 11 was finally derived from 8 by treatment with phosgene, and reaction of the chloroformate with thymidine (34% yield) [14].…”

“…Compound 18 was treated with paraformaldehyde in the presence of t-BuOK [30] to give the alcohol 17a in 86% yield. Protection of the OH group with t-BuMe 2 SiCl [26] [27] afforded the silyl ether 17b quantitatively. The position of the olefinic C C bond in compounds 17 was verified by 1 H-NMR analysis, and was in agreement with literature data [33].…”

The Belluš–Claisen Rearrangement

“…Thus, nearly complete (>98 %) 1,3‐chirality transfer occurred from the allylic C center of a CS bond in 41 to the stereogenic allylic C center in the new CC bond in the chiral thioester 42 , as determined by 1 H NMR spectroscopic shift experiments with ( R )‐(−)‐TFAE (2,2,2‐trifluoro‐1‐(9‐anthryl)ethanol; Table 1). 32, 33 Conceivably, the zwitterionic intermediate 38 (Figure 1) is involved in the suprafacial [3,3] bond reorganization step, thus leading to a new CC bond oriented exclusively “ cis ” with respect to the original CS bond. The stereochemical integrity of 42 was conserved during the subsequent dechlorination with Zn in AcOH at 100 °C to give the thioester 43 .…”

Die Belluš‐Claisen‐Umlagerung

“…1 H-NMR-spektroskopische Experimente mit dem Verschiebungsreagens (R)-(À)-TFAE (2,2,2-Trifluor-1-(9-anthryl)-ethanol; Tabelle 1) bestätigten den nahezu vollständigen (> 98 %) 1,3-Chiralitätstransfer vom allylischen Kohlenstoffzentrum einer C-S-Bindung in 41 zum stereogenen allylischen Kohlenstoffzentrum in der neu geknüpften C-C-Bindung des chiralen Thioesters 42. [32,33] Belluš-Claisen-Umlagerung Angewandte Chemie [3,3]-Umlagerungsschritt beteiligt, sodass die neue C-C-Bindung bezüglich der ursprünglichen C-S-Bindung ausschließ-lich "cis"-orientiert ist. Die stereochemische Integrität von 42 blieb bei der anschließenden Dechlorierung (Zn in AcOH, 100 8C) zum Thioester 43 erhalten.…”

“…1 H-NMR-spektroskopische Experimente mit dem Verschiebungsreagens (R)-(À)-TFAE (2,2,2-Trifluor-1-(9-anthryl)ethanol; Tabelle 1) bestätigten den nahezu vollständigen (> 98 %) 1,3-Chiralitätstransfer vom allylischen Kohlenstoffzentrum einer C-S-Bindung in 41 zum stereogenen allylischen Kohlenstoffzentrum in der neu geknüpften C-C-Bindung des chiralen Thioesters 42. [32,33] Möglicherweise ist die zwitterionische Zwischenstufe 38 (Abbildung 1) am suprafacialen (11) hoch chemoselektiv mit dem nucleophileren S-Atom, man erhält also ausschließlich den Thioester 48. [34] Die kürzlich beschriebene Pd-katalysierte Synthese von chiralen Allylthioethern könnte den Anwendungsbereich der Thia-BC-Umlagerung erweitern, da sie die Ausgangsstoffe leichter zugänglich macht.…”