Just add water to improve the performance of direct aldol reactions like that shown. Previously, aldehydes with high water‐affinity or ‐solubility were considered unsuitable for asymmetric synthesis.

No abstract

Four different protonic acids and 15 diamines were screened in the catalytic asymmetric direct aldol reaction of three different aldehydes in acetone.Recent advances in the asymmetric direct aldol reaction 1 have made reactions between two different carbonyl compounds more efficient and practical. Each reported method has notable advantages, but is still limited in scope. The main drawbacks arise from the inherent diversity of this process, and strongly depend on the carbonyl compounds employed. 2 The dehydration of aldol products is a major side-process. We describe here a diversity-based strategy 3 based on diamine salts 4 to address some of these issues. Thus, diamine-protonic acid catalysts, 5,6 which were found in a chiral diamine library, facilitate the catalytic asymmetric direct aldol reaction. Sequential treatment of a DMF solution of para-nitrobenzaldehyde (1a) (1 equiv) with p-TsOH×H 2 O (3 mol%), chiral diamine 4 (3 mol%) and acetone (27 equiv) at room temperature, followed by stirring at 40°C for 2 h, gave aldol adduct 2a in 19% yield with 83% ee, contaminated by dehydrated aldol adduct 3a (4%). The use of p-TsOH×H 2 O or the diamine alone led to negligible formation of 2a and 3a under similar conditions. The most suitable acid-diamine ratio was found to be 1:1 for effective rate acceleration; acid-diamine ratios greater or less than 1:1 significantly reduced the reaction rate. Due to the low reactivity in DMF, we next examined various solvents. Acetone was shown to be the best solvent as well as a nucleophile, and almost doubled the reaction rate. Furthermore, the negligible formation of side products other than 3a was ascertained by 1 H NMR analysis of the crude mixture which was obtained under otherwise identical reaction conditions (2a: 28% yield, 72% ee after 2 h at 40°C; 3a: 17%). Considering these results, we envisaged that the parallel library approach would be most suitable for lead optimization. Thus, 12 different diamines (secondary-primary, -secondary and -tertiary diamines) with a consistent secondary amino structure derived from L-proline, as well as three different diamines (primary-tertiary diamines) derived from D-phenylalanine, were synthesized 7 (Figure 1) and screened with a range of protonic acids and aldehydes.

Mit Wasser geht's besser! Das gilt für direkte Aldolreaktionen wie die gezeigte. Bisher erachtete man Aldehyde mit hoher Wasseraffinität oder Wasserlöslichkeit als für die asymmetrische Synthese nicht zugänglich.

Various alpha,beta-unsaturated carbonyl compounds were coordinated with aluminum tris(2,6-diphenylphenoxide) (ATPH) to give the corresponding Lewis acid-base complexes in a distinctive coordination fashion (selective coordination). ATPH recognizes carbonyl substrates and subsequently orients itself as it forms a stable complex through selective coordination with the carbonyl oxygen. Selective coordination also confers a conformational preference to each carbonyl compound under the steric and electronic influence of ATPH, which enables the vinylogous aldol reaction of alpha,beta-unsaturated carbonyl compounds to give the corresponding gamma-aldol products with different regio- and stereoselectivities.

[structure: see text] The structure of waol A has been revised from 1 to 6, the vinylogue of TAN-2483 A (5). Aldol reaction of 10b(c) with 2,4-hexadienal (11) affords 9b(c), which is subjected to iodoetherification with bis(sym-collidine)IPF(6) to provide 8b(c). Treatment with Et(3)N in CH(2)Cl(2) completes three-step syntheses of TAN-2483A (5) and waol A (6).

Die leichte Spirocyclisierung des verbrückten Bisalkylidens 1 lässt auf die Entwicklung einer allgemeine Strategie für die Synthese der Alkaloide der Palau'amin‐Familie hoffen. Die Besonderheiten dieses Modellsystems für die zentrale Einheit werden beschrieben.

Sesamin extends the lifespan of C. elegans through several dietary restriction-related signaling pathways, including processes requiring SIRT1, TOR, and AMPK.