Heteroatom-Directed, Palladium-Catalyzed, Regioselective Allylation:  Substitution with Inversion

Krafft, Marie E.; Wilson, Anne M.; Fu, Zice; Procter, Martin J.; Dasse, O. A.

doi:10.1021/jo9802372

Cited by 37 publications

(23 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The proposal that the alkoxide moiety directs the nucleophilic attack by shifting the position of the metal on the allyl fragment has precedent in the chemistry of palladium where neighboring groups have been found to exert this type of directing influence (77,78).…”

Section: Discussionmentioning

confidence: 99%

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Lautens

Fagnou²

2004

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

Catalyst and substrate studies have been performed on the rhodium-catalyzed asymmetric ring opening reaction. A working model is advanced that involves oxidative insertion with retention to form an organorhodium intermediate that then undergoes nucleophilic attack with inversion. Kinetic and competition experiments have uncovered evidence for a proton transfer step in the catalytic cycle that may activate both the allylrhodium intermediate and the nucleophile. We have also conducted experiments designed to understand which properties of the PPF-P t Bu2 ligand contribute to the high reactivities and enantioselectivities.W e have previously reported that chiral rhodium(I) catalysts induce ring opening oxa-and azabicyclic alkenes with a variety of soft nucleophiles such as alcohols, phenols, amines, anilines, malonates, and carboxylates in high yield and enantioselectivity (1-8). The products are generated by an S N 2Ј nucleophilic displacement of the bridgehead leaving group with inversion providing the 1,2-trans product as one regio-and diastereomer. The formation of the 1,2-trans products is atypical for ring opening reactions of oxabicyclic alkenes, which usually generate the syn-1,2 diastereomers via exo nucleophilic attack (1, 2). Furthermore, regio-and stereochemical results diverge from previously documented rhodium-catalyzed reactions with allylic carbonates (9-18). The observations obtained with oxabicyclic alkenes find little precedent when compared to other allylic functionalizations including those catalyzed by Pd (refs. 19 In this report we describe catalyst and substrate studies and advance a mechanistic working model that rationalizes the stereochemical outcome and other experimental observations (Scheme 1). We have also conducted experiments designed to understand the properties of the PPF-P t Bu 2 ligand that contribute to high reactivities and enantioselectivities.Experimental procedures and characterization data can be found in Supporting Text, which is published as supporting information on the PNAS web site. Ligand Studies: Variations on the Josiphos Template and Other Ligand MotifsSeveral structural elements are present on the PPF scaffold that could contribute to its successful application in these reactions (51-53). PPF has elements of central and planar chirality as well as two phosphine atoms that differ both sterically and electronically. Two methods were used to determine the influence of the ligand on the rate. In cases where a significant difference in rate was observed, percent conversion vs. time, as determined by crude 1 H NMR, was used to quantify the reactivity of the catalyst. In cases where a more precise measurement of rate was desired, kinetic runs were performed.By comparing the reactivity and enantioselectivity of ligands 3 and 4, two trends emerge (Scheme 2). First, by increasing the steric bulk ( t Bu Ͼ Cy) the enantioselectivity is increased from 88% with 3 to 96% enantiomeric excess (ee) with the bulkier t Bu 2 P ligand 4. This increase in enantioselectivity comes at ...

show abstract

Section: Discussionmentioning

confidence: 99%

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Lautens

Fagnou²

2004

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

show abstract

“…However, Krafft et al. found that this regioselectivity could be reversed by introducing suitable directing groups into the substrates . For example, when allylic acetates that contained a tertiary amine ( 70 a ) or thioether ( 70 b ) at the homoallylic position were applied in the allylation reaction, the favored branched products were achieved with branched/linear ratios from 19:1 to 10:1 (Scheme b).…”

Section: Coordination Interactionsmentioning

confidence: 99%

“…[33a] However, Krafft et al found that this regioselectivity could be reversed by introducing suitable directing groups into the substrates. [32,33] For example, whena llylic acetates that contained a tertiarya mine (70 a)o rt hioether (70 b)a tt he homoallylic position were applied in the allylation reaction, the favored branched products were achieved with branched/linear ratios from 19:1 to 10:1 (Scheme 18 b). Thea uthors also intensively investigated many other reaction parameters that affected the regioselectivity,i ncluding the directing group and its proximity to the allylic unit.…”

Section: Heteroatoms As the Electron-donating Unitmentioning

confidence: 99%

Non‐Bonding Interactions Enable the Selective Formation of Branched Products in Palladium‐Catalyzed Allylic Substitution Reactions

Wang

Xiao

2018

Chemistry An Asian Journal

View full text Add to dashboard Cite

Palladium-catalyzed allylic substitution reactions have become established as an important tool for the construction of carbon-carbon and carbon-heteroatom bonds in modern organic synthesis. However, controlling the regioselectivity of this type of transformation to afford chiral branched products, in addition to controlling the enantioselectivity, is a significant challenge. Excitingly, controlling nonbonding interactions between the substituents on the π-allyl-palladium intermediate and the nucleophile or palladium catalyst has been shown to be effective in achieving this goal. This Focus Review highlights representative advances in this field, according to the mode of non-bonding interaction, including hydrogen-bonding, electrostatic, and coordination interactions.

show abstract

“…Palladium-Catalyzed Allylic Alkylation Based on earlier work by the research groups of Kraft and Kocovsky, [66] Kazmaier and Lindner have developed a substrate-directed allylic alkylation in which chelated zinc enolates are employed as nucleophiles. Palladium-Catalyzed Allylic Alkylation Based on earlier work by the research groups of Kraft and Kocovsky, [66] Kazmaier and Lindner have developed a substrate-directed allylic alkylation in which chelated zinc enolates are employed as nucleophiles.…”

Section: Miscellaneous Directed Transition-metal-catalyzedmentioning

confidence: 99%

Removable Directing Groups in Organic Synthesis and Catalysis

2011

View full text Add to dashboard Cite

Directing groups have been widely used in recent years to achieve control over all aspects of reaction selectivity in a wide range of transformations involving transition-metal catalysis and organometallic reagents. In cases when the existing functional group within a substrate is unsuited to achieve efficient intramolecular delivery of a reagent or catalyst, the specific introduction of an appropriately designed removable reagent-directing group can be a solution to this problem. In this Review we give an overview of the state of the art in this area, including the stoichiometric and catalytic use of directing groups.

show abstract

Heteroatom-Directed, Palladium-Catalyzed, Regioselective Allylation: Substitution with Inversion

Cited by 37 publications

References 13 publications

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: Catalyst and substrate studies leading to a mechanistic working model

Non‐Bonding Interactions Enable the Selective Formation of Branched Products in Palladium‐Catalyzed Allylic Substitution Reactions

Removable Directing Groups in Organic Synthesis and Catalysis

Contact Info

Product

Resources

About