Aldolreaktionen in der Totalsynthese von Polyketiden

Abstract

Die Aldolreaktion gehört zu den wichtigsten Methoden der organischen Synthesechemie für den stereoselektiven Aufbau von polyketiden Naturstoffen. Dabei bedient sich die Natur gleichermaßen wie der präparativ arbeitende Chemiker dieser fundamentalen Reaktion. Die rasante Entwicklung auf dem Gebiet der stereoselektiven Aldolreaktionen während der letzten 30 Jahre führte zur Totalsynthese vieler komplexer Naturstoffe. Dieser Beitrag illustriert anhand ausgewählter Totalsynthesen von Naturstoffen diese neuartigen Varianten der Aldoladdition. Dabei werden Aldoladditionen, die sich unterschiedlicher Metallenolate bedienen, ebenso behandelt wie metallkomplexkatalysierte, organokatalytische sowie biokatalytische Methoden.

A Soft Vinyl Enolization Approach to α‐Acylvinyl Anions: Direct Aldol/Aldol Condensation Reactions of (E)‐β‐Chlorovinyl Ketones

“…Although further mechanistic studies remain to be conducted, our preliminary findings suggest the base-promoted vinylogous aldol-type reaction of cummulenol(ate)s as a possible reaction pathway. Given the widespread applicability of enols and metal enolates in stereoselective C À C bond forming reactions, [2] we anticipate that the synthetic scope of cummulenol(ate)s can be further expanded. Accordingly, our current efforts are directed towards addressing the low diastereoselectivity issue by using stereoselective isomerization under Brønsted base catalysis, and further broadening the synthetic utility of cummulenol(ate)s in other CÀC bond forming reactions.…”

“…The enol and metal enolate forms of carbonyl compounds constitute one of the most widely used nucleophiles in the CÀC bond forming strategies that readily accommodate various electrophiles as reaction partners. [1] Whereas regio-and stereoselective enol(ate) formation of carbonyl compounds with a-C(sp 3 ) À H bonds has been achieved with an increasing degree of sophistication, [2] the generation of corresponding enol and enolate forms of carbonyl compounds with a-C(sp 2 )ÀH bonds (such as allenol and allenolates) has been limited to a few exceptional cases of a,b-unsaturated carbonyl compounds (Scheme 1). [3] The unfavorable orbital overlap between the p CÀO bonding orbital and the s * aÀ CÀH anti-bonding orbital in a conjugate system makes the a-vinyl deprotonation extremely challenging under mild reaction conditions.…”

Katalytische enantioselektive konjugierte 1,6‐Addition von Grignard‐Reagentien an lineare Dienoate

“…Da chirale methylsubstituierte Alkylketten häufig in Naturstoffen vorkommen, [25] ist die AKA mit MeMgBr besonders interessant.…”

Ugi/Aldol Sequence: Expeditious Entry to Several Families of Densely Substituted Nitrogen Heterocycles

“…Given its outstanding importance in the preparation of both top-selling pharmaceuticals 16 and natural products 17 , we were therefore enticed to investigate the possibility to merge the exploratory power of the U-4CR with the potential to convert Ugi products into novel appealing heterocyclic chemotypes offered by the aldol condensation. In order to endow the multicomponent reaction (MCR) product with functionalities suitable to participate in an aldol condensation, pyruvic aldehyde and phenylglyoxylic acid were employed, along with benzylamine and n- butylisonitrile (Scheme 1).…”