Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between α,β- and β,γ-Butenolides and Aldimines

Abstract

We report a Zn-ProPhenol catalyzed reaction between butenolides and imines to obtain tetrasubstituted vinylogous Mannich products in good yield and diastereoselectivity with excellent enantioselectivity (97 to >99.5% ee). Notably, both α,β- and β,γ-butenolides can be utilized as nucleophiles in this transformation. The imine partner bears the synthetically versatile N-Cbz group, avoiding the use of the specialized aryl directing groups previously required in related work. Additionally, the reaction can be performed on gram scale with reduced catalyst loading as low as 2 mol %. The functional group-rich products can be further elaborated using a variety of methods.

Dinuclear Metal‐ProPhenol Catalysts: Development and Synthetic Applications

“…Recently, Trost and co-workers reported a Zn-ProPhenol catalyzed reaction between butenolides 146 and imines 124 c to obtain tetrasubstituted vinylogous Mannich products 147 in good yield and excellent diastereo-and enantioselectivity (Scheme 35). [67] Unlike most reported systems, this process does not require pre-activation of the butenolides as siloxyfurans. [68] Moreover, both a,b-and b,g-butenolides were equally competent nucleophiles with a wide range of substitution at the 4-and 5-positions rather than being limited to a simple methyl group or hydrogen.…”

“…Recently, Trost and co‐workers reported a Zn‐ProPhenol catalyzed reaction between butenolides 146 and imines 124 c to obtain tetrasubstituted vinylogous Mannich products 147 in good yield and excellent diastereo‐ and enantioselectivity (Scheme ) . Unlike most reported systems, this process does not require pre‐activation of the butenolides as siloxyfurans .…”

Zweikernige Metall‐ProPhenol‐Katalysatoren: Entwicklung und Anwendungen in der Synthese

“…Kürzlich haben Trost und Mitarbeiter eine Zn‐ProPhenol‐katalysierte Reaktion zwischen Butenoliden 146 und Iminen 124 c berichtet, bei der sie tetrasubstituierte vinyloge Mannich‐Produkte 147 in guten Ausbeuten und exzellenten Diastereo‐ und Enantioselektivitäten erhielten (Schema ) . Im Unterschied zu den meisten anderen bekannten Systemen erfordert dieser Prozess keine Präaktivierung der Butenolide als Siloxyfurane .…”

“…a-Verzweigte Aldehyde 143 stellten gleichfalls reaktionsfähige Nukleophile dar, um eine Reihe chiraler b-Aminoaldehyde 144 zu synthetisieren. [66] Anschließend kçnnen die Addukte 144 im Eintopf mit einem zweiten Nukleophil [67] Im Unterschied zu den meisten anderen bekannten Systemen erfordert dieser Prozess keine Präaktivierung der Butenolide als Siloxyfurane. [68] Zudem erwiesen sich a,b-wie auch b,g-Butenolide als gleichermaßen reaktionsfähige Nukleophile mit einer großen Substituentenvielfalt an den 4-und 5-Posi-tionen, im Unterschied zu einer Limitierung auf eine einfache Methylgruppe oder Wasserstoff.…”

Direct Catalytic Asymmetric Vinylogous Additions of α,β‐ and β,γ‐Butenolides to Polyfluorinated Alkynyl Ketimines

“…Furthermore, the butenolides could be unmasked to give access to 1,2‐amino alcohols, another pharmaceutically and synthetically relevant motif . In addition, our recent success shows that Zn‐ProPhenol can activate butenolides of various substitutions for reaction with aldimines whereas other Mannich methods are mainly restricted to α‐angelica lactone or 2( 5H )‐furanone, or require preactivation to the siloxyfurans . However, our process must overcome the potential 1,4‐addition onto the alkynyl ketimines as well as the steric hindrance during the construction of two contiguous tetrasubstituted stereocenters, which remains rare and difficult in modern asymmetric catalysis…”