On Asymmetric Induction in Allylic Alkylation via Enantiotopic Facial Discrimination

Trost, Barry M.; Krische, Michael J.; Radinov, Roumen; Zanoni, Giuseppe

doi:10.1021/ja960649x

Cited by 133 publications

(52 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3). 21) On the other hand, the chiral racemic substrates 15a, b gave the same cyclized product with only 4-6% ee. This difference between the achiral and chiral precursors supports the interpretation that the enantiodiscrimination is the ionization event.…”

Section: Type a Enantiodiscriminationmentioning

confidence: 97%

Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Trost

2002

Chem. Pharm. Bull.

Self Cite

304

View full text Add to dashboard Cite

Chiral compounds have many applications. None are more important than those related to biological targets. The chiral nature of biological receptors make chiral ligands common objectives as pharmaceuticals and agrichemicals. Thus, developing efficient synthetic methods to such compounds represents an important challenge. In spite of great advances, resolution methods still frequently represent the most economical method for commercial production in spite of the fact that the theoretical yield of the single desired enantiomer cannot exceed 50% unless the opposite enantiomer can be converted to the desired one. Using starting materials from the chiral pool also constitutes a common strategy. More recently, attention has shifted to inducing chirality into achiral precursors. Two tacts have been explored. In one, chiral auxiliaries, normally emanating from the chiral pool, are covalently attached to prochiral substrates.1) The advantage of this approach is the high degree of success in transmitting chiral information in this more controlled strategy. However, it suffers from numerous drawbacks. First, it requires stoichiometric amounts of the chiral auxiliary which ultimately is not part of the final product. It also requires additional steps to add and subsequently remove the chiral auxiliary. Clearly, the conceptually most attractive strategy is employing asymmetric catalytic reactions. 2)Some of these have achieved great success. Two of the most successful have been asymmetric catalytic hydrogenation and asymmetric catalytic oxidation of alkenes, notably epoxidation. These two reactions, in addition to virtually every other asymmetric catalytic reaction, share a common feature-the enantiodiscriminating event involves recognizing the enantiotopic faces of a prochiral p-unsaturation such as a carbonyl group or a double bond. Furthermore, each of these reactions also involve formation of just one bond type-a C-H bond in the case of hydrogenation and a C-O bond in the case of oxidation.Catalytic asymmetric allylic alkylation differs from virtually all other catalytic processes in two important ways. In the first, there are many enantiodiscriminating mechanisms, not just one. As shown in Fig. 1, there are at least five such mechanisms. As in most other catalytic asymmetric reactions, differentiating the enantiotopic faces of a p-unsaturation is one mechanism (Fig. 1, A). A second mechanism is differentiating enantiopic leaving groups (Fig. 1, B). Mechanism C involves differentiating enantiotopic termini of a pallylmetal intermediate. Since this intermediate derives from a chiral racemic precursor in which the chirality of the substrate is lost, this deracemization constitutes a dynamic kinetic asymmetric transformation (DYKAT). Mechanism D is a varient of mechanism A wherein the p-allylmetal intermediates interconvert faster than they are attacked by a nucleophile and asymmetric induction derives from differential rates of reaction of the two diastereomeric intermediates. This mechanism allows employment of either an ...

show abstract

Section: Type a Enantiodiscriminationmentioning

confidence: 97%

Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Trost

2002

Chem. Pharm. Bull.

Self Cite

304

View full text Add to dashboard Cite

show abstract

“…[20][21][22][23][24] The regioselectivities in reactions using rhodium, [25][26][27][28][29][30][31][32][33] iridium, [34][35][36][37][38] and ruthenium [39][40][41] complexes are quite different from those of palladium-catalyzed reaction. Therefore, chiral iridium complexes controlling regio-and enantioselectivities have been a subject of current interest.…”

Section: Resultsmentioning

confidence: 99%

Regio- and Enantioselective Allylic Substitution with Less Active N- or O-Nucleophiles Catalyzed by Iridium-Complex of Bis(oxazolinyl)pyridine

Miyabe

Moriyama

Takemoto

2011

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Enantioselective transition metal-catalyzed allylic substitutions have been developed as fundamentally important crosscoupling reactions. [1][2][3][4][5][6][7][8] In general, the heteroatom nucleophiles in these reactions have been largely limited to alkylamines, anilines, carboxylates and phenols. Our laboratory is interested in searching the synthetically useful heteroatom nucleophiles for the synthesis of functionalized allylic compounds (Fig. 1).9) As our successful examples, we have recently reported the utility of oximes 1 and guanidines 5 and 6 as nucleophiles in the transition metal-catalyzed allylic substitution. [10][11][12][13][14] Hydroxylamines are also attractive synthetic reagents for allylic substitution, since they have nitrogen and oxygen atoms as nucleophiles. However, the allylic substitution with hydroxylamines has not been studied well and is limited to a simple palladium-catalyzed amination 15,16) ; thus, there are no reports on asymmetric reactions. We have recently reported that hydroxylamines 2 and 3 having an N-electron-withdrawing substituent, also known as hydroxamic acids, act as reactive oxygen nucleophiles in the enantioselective allylic substitution ( Fig. 1). 17,18) As a part of our program directed toward searching the synthetically useful heteroatom nucleophiles, we describe in detail the study of hydroxylamines 4 as nitrogen nucleophiles in the regio-and enantioselective iridium-catalyzed allylic substitutions. 19) In this study, we also expected that comparison with alkylamines, p-anisidine, and 4-methoxyphenol would lead to informative suggestions regarding the asymmetric reaction using the iridium complex of pybox (bis(oxazolinyl)pyridine) ligand. Results and DiscussionControlling both regio-and enantioselectivities has been of great importance in the allylic substitution of unsymmetrical substrates with heteroatom nucleophiles. [20][21][22][23][24] The regioselectivities in reactions using rhodium, [25][26][27][28][29][30][31][32][33] iridium, [34][35][36][37][38] and ruthenium [39][40][41] complexes are quite different from those of palladium-catalyzed reaction. Therefore, chiral iridium complexes controlling regio-and enantioselectivities have been a subject of current interest. Recently, we reported that the iridium-complex of pybox catalyzed allylic substitution of unsymmetrical substrates to form branched products with good enantioselectivities. 13,14,17,19) Prior to exploring the enantioselective reaction, we first investigated the viability of hydroxylamine 4A having N-benzoyl and O-benzyl groups (Chart 1). Although the reaction of 4A with carbonate 7 was less effective in the absence of a base, the reaction of 4A with acetate 8 proceeded smoothly by employing Et 2 Zn as a base to give the branched product 9Aa in 60% yield without formation of the linear product.Based on these results, we next investigated iridium-catalyzed asymmetric allylic substitution with hydroxylamine 4A under basic conditions (Chart 2). In this study, phosphate 10a was employed as an unsymm...

show abstract

“…Natriumsulfinat Das verzweigte Allylsulfon 114 wurde durch Reaktion von linearem (E)-Crotylmethylcarbonat (92 g) mit Natriumbenzolsulfinat und dem Liganden (R,R)-L130 hergestellt (Schema 41). [192] Tabelle [154] 3-Methylbuten-2-ylacetat (122), 3-Methylbuten-3-ylacetat (125) und 3-Phenylbuten-3-ylacetat (126) reagierten mit 99 a in Gegenwart von L130 mit höherer Enantioselektivität zu den ebenfalls linearen Verbindungen 123 und 127. Interessanterweise entsteht bei der Umsetzung der sterisch nur wenig gehinderten Acetate 122 und 125 auch das verzweigte Produkt 124, allerdings mit niedrigen Ausbeuten und Enantioselektivitäten (Schema 44).…”

Section: Amineunclassified

“…das monocyclische Amin 178 (84 % Ausbeute, 92 % ee; Schema 62). [192] Trost et al entdeckten, dass auch die Aminogruppe in der durch rutheniumkatalysierte Cyclometallierung von 179 und 180 erhaltenen Zwischenverbindung 183 intramolekular mit . [214] Das bicyclische Tosylamid 185 (88 % ee) wurde in 90 % Ausbeute durch intramolekulare Aminierung des racemischen Aminocyclooctencarbonats 184 in Gegenwart des Liganden L180 gebildet (Schema 64).…”

Section: Cycloallylierungen Mit Amiden Oder Aminenunclassified

Metallkatalysierte enantioselektive Allylierungen in der asymmetrischen Synthese

Lu¹,

Ma²

2007

Angewandte Chemie

431

View full text Add to dashboard Cite

Durch metallkatalysierte enantioselektive Allylierungen, die unter Substitution von Allylmetall‐Zwischenstufen mit zahlreichen Nucleophilen oder als allylische SN2′‐Substitution verlaufen, werden in Gegenwart ausgewählter Kombinationen aus Metallen und chiralen Liganden C‐H‐, C‐C‐, C‐O‐, C‐N‐, C‐S‐ und andere Bindungen mit sehr hoher asymmetrischer Induktion geknüpft. Die Reaktionen sind mit einer Vielzahl funktioneller Gruppen vereinbar und wurden erfolgreich in der Synthese vieler Naturstoffe und neuer chiraler Verbindungen verwendet.

show abstract

On Asymmetric Induction in Allylic Alkylation via Enantiotopic Facial Discrimination

Cited by 133 publications

References 19 publications

Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Regio- and Enantioselective Allylic Substitution with Less Active N- or O-Nucleophiles Catalyzed by Iridium-Complex of Bis(oxazolinyl)pyridine

Metallkatalysierte enantioselektive Allylierungen in der asymmetrischen Synthese

Contact Info

Product

Resources

About