Enantioselective Synthesis of α-Methylene-β-hydroxy Carboxylic Acid Derivatives via a Diastereoselective Aldol/β-Elimination Sequence: Application to the C(15)−C(21) Fragment of Tedanolide C

Abstract

An enantioselective synthesis of α-methylene-β-hydroxy carboxylic acid derivatives via a highly diastereoselective, one-pot syn-aldol and β-elimination sequence utilizing the chiral β-(phenylselenyl)propionyl imide 15 is described. This new method, which constitutes an alternative to the Baylis-Hillman reaction, has been applied to the synthesis of the C(15)-C(21) fragment of tedanolide C.

Cooperative Dehydrogenation of N‐Heterocycles Using a Carbon Nanotube–Rhodium Nanohybrid

“…B. alloc, MMTr) richtete sich unser Augenmerk auf die Arbeiten von Roush, der über die selektive Schützung der C17‐OH‐Gruppe als TES‐Ether berichtete. Unter Verwendung dieser Arbeitsvorschrift konnten wir schließlich die C17‐OH‐Gruppe von 11 8a,b mit TESCl bei −78 °C erfolgreich schützen. Die Behandlung mit DDQ unter wasserfreien Bedingungen lieferte schließlich das entsprechende PMP‐Acetal, das mit DIBAL‐H regioselektiv geöffnet werden konnte (Schema ).…”

The Synthesis and Biological Evaluation of Desepoxyisotedanolide and a Comparison with Desepoxytedanolide

“…After unsuccessful experimentation with various protecting groups (e.g., alloc, MMTr) our attention was caught by a method published by the Roush group, which reported the selective protection of the C17 hydroxy group as the TES ether. By following their protocol, selective protection at the C17 hydroxy group of 11 8a,b was accomplished through treatment with triethylsilyl chloride. Subsequent treatment with DDQ under anhydrous conditions generated the corresponding PMP acetal, followed by regioselective reductive acetal opening with DIBAL‐H (Scheme ).…”

“…Based on studies performed with radioactively labeled derivatives of tedanolide,F usetani confirmed that tedanolide (1)b inds to the 60S ribosomal subunit. [2,5 ] Thes tructural complexity of tedanolides has attracted the attention of several research groups, [6] with total syntheses put forward by the groups of Smith, [7] Roush [8] and Kalesse. [9] Thes ignificant structural characteristics of the tedanolides are an 18-membered macrolactone and an epoxide on the side chain.…”

“…Thea ldol reaction between fragments 9 and 10 was achieved by using the conditions provided by Roush. [8] Ketone 9 was treated with LiHMDS at À78 8 8Cand aldehyde 10 was added dropwise to the reaction mixture,w hich was quenched after 15 min with brine (Scheme 1). First, the aldol products 13 (d.r.2.5:1), unreacted ketone 9,and the aldehyde 10 were separated by column chromatography.Asecond separation by normal-phase HPLC with EtOAc and heptane as eluent was required to separate the diastereomeric aldol products.The observed selectivity of 2.5:1 can be rationalized by the competing effects of the Felkin-directing centre in the a position and the Felkin-opposing configuration at C15.…”

Chiral Polyoxygenated Tertiary Alcohols through Kiyooka Aldol Reaction

“…An example of a non-aldol-strategy for such tertiary alcohols was put forward by Roush and Barth in the course of their efforts towards tedanolide C. They used a Sharpless asymmetric dihydroxylation of an advanced intermediate to establish the required tertiary and primary alcohol moieties. 6 In contrast to the above mentioned aldol strategies, enolates of αoxygenated carbonyl compounds can react with nearly all aldehydes. Both of these approaches can be performed with enol ethers or ketene acetals.…”