Highly Diastereoselective Synthesis of 2,6‐Di[1‐(2‐alkylaziridin‐1‐yl)alkyl]pyridines, Useful Ligands in Palladium‐Catalyzed Asymmetric Allylic Alkylation

Abstract

C 2 -Symmetrical, enantiopure 2,6-di[1-(1-aziridinyl)alkyl]pyridines (DIAZAPs) were prepared by a high-yielding, three-step sequence starting from 2,6-pyridinedicarbaldehyde and (S)-valinol or (S)-phenylglycinol. The new compounds were tested as ligands in palladium-catalyzed allylation of carbanions in different solvents. Almost quantitative yield and up to 99 % enantiomeric excess were obtained in the reactions of the enolates derived from malonate, phenyl-and benzylmalonate dimethyl esters with 1,3-diphenyl-2-propenyl ethyl carbonate.

Metal‐Catalyzed Enantioselective Allylation in Asymmetric Synthesis

“…[54,56,63,141,189,202] However, excellent regio-and stereoselectivities were observed for the reaction of 4-tert-butylphenol with unsymmetrical 1-alkyl-3-phenylallyl carbonates 142 to afford 143 a in very high yield and stereoselectvity. A complete reversal of regioselectivity was observed when aniline was used as the nucleophile, and afforded 144 b in 52 % yield and 98 % ee (Scheme 51).…”

“…[141] The reaction of CH 2 (CO 2 Me) 2 , AcNHCH-(CO 2 Me) 2 , CF 3 CONHCH(CO 2 Me) 2 , or PhCONHNH 2 with 3-penten-2-yl acetate in the presence of the chiral phosphanebisoxazoline L154 afforded the corresponding products in 98 % yield and 85-95 % ee (Table 2). [144] The reaction of dimethyl malonate with 1,3-diphenylallyl pivalate in the presence of chiral imino-phosphanyl dendrimer L155, afforded product B1 in 95 % yield and 95 % ee (Scheme 14).…”

Effective Chiral Ferrocenyl Phosphine‐Thioether Ligands in Enantioselective Palladium‐Catalyzed Allylic Alkylations

“…The development of Pd-catalyzed allylic substitution of unsymmetrical substrates with high regioselectivity and enantioselectivity is a current interest since, in the Pd-catalyzed allylic alkylations, nucleophiles would preferentially attack at the least hindered allylic carbon to give achiral linear or less hindered products. [24,25] Recently, bulky and electronically poor phosphorus ligands were found to be efficient in the allylic alkylation of achiral linear or racemic branched allylic acetate 11, and highly regioselective and enantioselective branched alkylated products 12a were obtained.…”

Metallkatalysierte enantioselektive Allylierungen in der asymmetrischen Synthese

“…[54,56,63,141,189,202] Die Reaktion von 4-tert-Butylphenol mit den unsymmetrischen 1-Alkyl-3-phenylallylcarbonaten 142 führte dagegen hoch regio-und stereoselektiv und mit sehr hoher Ausbeute zu 143 a. Mit Anilin als Nucleophil kehrte sich die Regioselektivität vollständig um, und 144 b wurde in 52 % Ausbeute und mit 98 % ee erhalten (Schema 51). [203] Gais et al berichteten, dass die dynamische kinetische Racematspaltung der unsymmetrischen 1,3-disubstituierten Allylcarbonate 145 a,b mit H 2 O zu den optisch aktiven Allylalkoholen 146 a,b hoch enantioselektiv verläuft, während Substrate mit R = CN oder P(O)(OEt) 2 nur geringe Enantioselektivitäten ergeben.…”