Palladium‐Catalyzed Asymmetric Allylic Alkylation of Ketone Enolates

Abstract

Palladium-catalyzed asymmetric allylic alkylation of nonstabilized ketone enolates to generate quaternary centers has been achieved in excellent yield and enantioselectivity. Optimized conditions consist of performing the reaction in the presence of two equivalents of LDA as base, one equivalent of trimethytin chloride as a Lewis acid, 1,2-dimethoxyethane as the solvent, and a catalytic amount of a chiral palladium complex formed from pi-allyl palladium chloride dimer 3 and cyclohexyldiamine derived chiral ligand 4. Linearly substituted, acyclic 1,3-dialkyl substituted, and unsubstituted allylic carbonates function well as electrophiles. A variety of alpha-tetralones, cyclohexanones, and cyclopentanones can be employed as nucleophiles. The absolute configuration generated is consistent with the current model in which steric factors control stereofacial differentiation. The quaternary substituted products available by this method are versatile substrates for further elaboration.

Metal‐Catalyzed Enantioselective Allylation in Asymmetric Synthesis

“…[154] In contrast, the reaction of branched trimethylsilyl-substituted allylic acetate 94 b afforded the linear product 101 with a much higher enantioselctivity (Scheme 34). [154] Similar reactions of a-substituted cyclic ketones 44 [161] and 103 [163] with (E)-2-butenyl carbonate (92 g) also afforded linear products: the a,a-disubstituted cyclic ketones 102 and 104 were formed with 90 and 82 % ee, respectively (Scheme 35). Morpholine derivatives 109 a,b can be constructed with 90-94 % ee by the asymmetric intermolecular and subsequent intramolecular allylic substitution of 1,4-diacetoxy-(Z)-2-butene (107) with aminoalcohols 108 a [178] and 108 b [179] as well as L168 and L130, respectively (Scheme 37).…”

“…[154,155] The reaction of the lithium enolate of a-methylbenzocyclohexanone (44 a) with 2-methylallyl carbonate in the presence of (S,S)-L130 yielded (R)-amethyl-a-(2-methylallyl)benzocyclohexanone (70) with 47 % ee; however, the same reaction with L162 afforded the same product (R)-70 with 87 % ee. [161,162] The reaction of trimethylsilyl enol ether of a-methylcyclohexane 46 a with bis(2-methylallyl) carbonate and the decarboxylative reaction of 2-methylallyl-2-methylcyclohex-1-enyl carbonate (74) in the presence of (S)-L28 c afforded the same product (S)-71 with 91 % ee. [165] The decarboxylation of chloride 75 led to the formation of product (S)-76 in 87 % yield and 91 % ee.…”

Stereoselective Construction of Quaternary Stereocenters

“…[25] As a representative example, the synthesis of hamigeran B (30), a marine natural product with powerful activity against herpes and polio viruses, by Trost and co-workers is briefly mentioned here (Scheme 7). [26] The stereoinducing key step is a Pd-catalyzed asymmetric allylation of simple ketone enolates, [27] which is based on in situ formation of the trimethylstannyl enol ether 24. By application of the "standard Trost ligand" 25, the obvious disadvantage of using stoichiometric tin reagents is compensated for by the high yield and stereoselectivity of product 26 (77%, 93% ee).…”

Metallkatalysierte enantioselektive Allylierungen in der asymmetrischen Synthese

“…[154,155] Das Lithiumenolat von a-Methylbenzocyclohexanon (44 a) reagierte mit 2-Methylallylcarbonat in Gegenwart von (S,S)-L130 zu (R)-a-Methyl-a-(2-methylallyl)benzocyclohexanon (70, 47% ee), während durch die analoge Reaktion mit L162 das gleiche Produkt (R)-70 mit 87 % ee entstand. [161,162] (S)-71 wurde mit jeweils 91 % ee durch Reaktion des TrimethylsilylEnolethers 46 a von a-Methylcyclohexan mit Bis(2-methylallyl)carbonat oder durch Decarboxylierung von 2-Methylallyl-2-methyl-1-cyclohexenylcarbonat (74) in Gegenwart von (S)-L28 c erhalten. [165] Die Decarboxylierung des Chlorids 75 führte in 87 % Ausbeute und mit 91 % ee zu (S)-76.…”

“…[158] [154] Deutlich enantioselektiver verlief die Umsetzung des verzweigten Trimethylsilyl-Allylacetats 94 b zum linearen Produkt 101 (Schema 34). [154] Die ähnlichen Reaktionen der a-substituierten cyclischen Ketone 44 [161] und 103 [163] mit (E)-2-Butenylcarbonat (92 g) führten ebenfalls zu linearen Produkten: Die a,a-disubstituierten cyclischen Ketone 102 und 104 werden mit 90 bzw. und den Liganden L168 bzw.…”