Subtle Variations in the Long-Range Transmission of Stereochemical Information: Matched and Mismatched Aldol Reactions

Abstract

In this paper we describe findings with respect to an important question in stereospecific synthesis, that is, how might remote stereogenic loci influence the diastereofacial sense in which covalent bond formation occurs. To address this type of issue in concrete rather than abstract terms, we focused on the very promising antitumor agents, the epothilones (such as epothilone B (1), shown in Scheme 1). These compounds have stimulated a great deal of research from the point of view of total synthesis. [1±6] In this paper we do not directly address the total synthesis problem per se. Rather, we focus on the construction of the C6ÀC7 bond in the acyl sector en route to the natural products, as a paradigm for accomplishing high orders of selection by long-range induction.By way of background we note that, originally, [1a, 1c] the stereochemical information for building the ªacylº sector of the epothilones (see 2 in Scheme 1) was stored in dihydropyrone 5 which itself arose from a cyclocondensation reaction of enantiomerically pure 3 and diene 4. In our second-generation synthesis, [7] the enantiomerically homogenous 6 reacted with Me O

Aldolreaktionen in der Totalsynthese von Polyketiden

“…Im Weiteren werden Aldoladditionen mit chiralen Titanenolaten beschrieben. Ein erstes Beispiel hierfür stammt aus der Totalsynthese des Epothilons 490 von Danishefsky et al (Schema 12) 60–63. Für diese Totalsynthese verwendeten die Autoren die zuverlässige und weit verbreitete Titanenolat‐Aldolreaktion nach Duthaler.…”

“… Totalsynthese von Epothilon 490 nach Danishefsky et al60–63 Troc=2,2,2‐Trichlorethoxycarbonyl; Cp=Cyclopentadienyl. …”