Stereocontrolled Oxidative Addition of Zerovalent Molybdenum to Enantiomerically Pure Allylic Acetates with Either Inversion or Retention at the Stereogenic Center

Ward, Yancey D.; Villanueva, Lawrence A.; Allred, Gary D.; Liebeskind, Lanny S.

doi:10.1021/ja952938b

Cited by 52 publications

(55 citation statements)

References 35 publications

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“…Of the metals that are known to catalyze allylic substitutions, only molybdenum has been shown to oxidatively add with retention of configuration (62,63). Precoordination of the Lewis basic leaving group to the Lewis acidic molybdenum metal before alkene binding is believed to be responsible for this outcome (64,65). The putative predisposition of the oxabicyclic core to bind to the rhodium metal on its exo face through the alkene and the oxygen atom may predispose the complex to this type of reactivity.…”

Section: Discussionmentioning

confidence: 99%

“…The putative predisposition of the oxabicyclic core to bind to the rhodium metal on its exo face through the alkene and the oxygen atom may predispose the complex to this type of reactivity. Precoordination of the metal to the alkene and the leaving group has been used to rationalize the stereochemical dichotomy between palladium and molybdenum catalyzed reactions (64)(65)(66)(67)(68)(69)(70).…”

Section: Discussionmentioning

confidence: 99%

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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

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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 ...

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Section: Discussionmentioning

confidence: 99%

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

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“…41 The previously disclosed route to the enantiomerically pure version of 3 41 relied upon a known synthesis of allylic acetate (S)-12. 42 The preparation of (S)-12 has now been significantly enhanced (Scheme 3).…”

Section: Synthesis Of Lactonyl and Lactamyl Scaffolds 3 Andmentioning

confidence: 99%

“…Treatment of compound (S)-12 with 1.0 equiv of (toluene)Mo(CO) 3 46 in dichloromethane at room temperature over 4 days, followed by the addition of potassium hydridotris(pyrazolyl) borate (K + TP − ), 47 provided complex (+)-3 in 62% yield with excellent enantiomeric excess (97% ee) via a retention of configuration pathway. 41 The synthesis of racemic lactamyl scaffold (±)-4 has also been dramatically improved compared to the previously described 11-step process. 48 Racemic (±)-4 is now available by a straightforward 4-step sequence.…”

Section: Synthesis Of Lactonyl and Lactamyl Scaffolds 3 Andmentioning

confidence: 99%

Organometallic Enantiomeric Scaffolding: General Access to 2-Substituted Oxa- and Azabicyclo[3.2.1]octenes via a Brønsted Acid Catalyzed [5 + 2] Cycloaddition Reaction

Garnier

Liebeskind

2008

J. Am. Chem. Soc.

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Abstract6-Substituted TpMo(CO) 2 (η-2,3,4-pyranyl)-and TpMo(CO) 2 (η-2,3,4-pyridinyl) scaffolds (Tp = hydridotrispyrazolylborato) function as reaction partners in an efficient regio-and stereocontrolled synthesis of functionalized oxa-and azabicyclo[3.2.1]octenes through a novel Brønsted acidcatalyzed [5+2] cycloaddition reaction. Excellent exo-selectivities are obtained and the reaction gives products with complete retention of enantiomeric purity when carried out with chiral, non-racemic scaffolds. The substituent at C-6 of the η 3 -coordinated heterocyclic scaffold not only influences [5 +2] reactivity but also plays a critical role in the demetalation step directing the reaction to only one of two possible products.

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“…Faller and Linebarrier (49), Rubio and Liebeskind (50), and Kuhl et al (51) have shown that oxidative addition in stoichiometric reactions of Mo(CO) 3 (MeCN) 3 with cyclic and acyclic allylic acetates proceeds with retention of configuration. On the other hand, Ward et al (52) discovered the stereochemistry of the oxidative addition is influenced by steric factors and experimental conditions, and oxidative addition of a single substrate can follow either an inversion or retention pathway, depending on the solvent and concentration, suggesting both stereochemical avenues may be available to Mo-catalyzed reactions.…”

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confidence: 99%

Mechanistic studies of the molybdenum-catalyzed asymmetric alkylation reaction

Hughes

Lloyd‐Jones

Krska

et al. 2004

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

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M etal-catalyzed asymmetric allylic alkylations are widely used in organic synthesis as efficient and practical methods to form carbon-carbon bonds with high enantio-and regioselectivity. Early work in this area focused on Pd complexes as catalysts, but their utility in organic synthesis was limited because, in general, unsymmetrical substrates afforded the achiral linear product (1-5). More recently, a limited number of ligands have been designed such that the branched product is now accessible with high enantiomeric excess (ee) by using Pd catalysis (6-9). Additionally, several other transition metals and ligands have been developed to regioselectively provide the branched product. These reactions can be grouped into two categories: (i) those that retain the stereochemistry of the branched substrate, and (ii) those in which the stereochemistry is lost. When starting with branched substrates, Ru (10-13), Rh (14,15), Fe (20,21), and W (22) complexes generally provide product wherein the stereochemistry of the substrate is retained, although recent exceptions have now been reported (23,24). These reactions may proceed by means of intermediates in which isomerization (K eq in Scheme 1) is slow relative to nucleophilic reaction. In contrast, Mo-based catalysis (25-39) proceeds with loss of substrate stereochemistry and provides the opportunity in reactions with asymmetric ligands to obtain high product ee, starting with either the linear substrate or racemic branched product (Scheme 1). These reactions proceed by a dynamic kinetic asymmetric transformation (40) with rapid equilibration of the two diastereomeric -allyl complexes before nucleophilic attack (Scheme 1).The stereochemistry of the two steps shown in Scheme 1 is arbitrarily shown as retention for oxidative addition and retention for the nucleophilic displacement. Extensive work on the Pd-catalyzed allylic alkylation has shown that the overall stereochemical outcome is generally retention, with the two steps of the process both proceeding with inversion (41-46). More recently, the Ir-catalyzed alkylation has also been shown to proceed by inversion-inversion in constrained systems (19). For the Mo-catalyzed reaction, Trost and coworkers (47, 48) have determined that the reaction proceeds with overall retention, but the stereochemistry of each step in the reaction has not been elucidated.A few studies have been carried out to determine the stereochemistry of the oxidative addition reaction in the Mocatalyzed reaction. Faller and Linebarrier (49), Rubio and Liebeskind (50), and Kuhl et al. (51) have shown that oxidative addition in stoichiometric reactions of Mo(CO) 3 (MeCN) 3 with cyclic and acyclic allylic acetates proceeds with retention of configuration. On the other hand, Ward et al. (52) discovered the stereochemistry of the oxidative addition is influenced by steric factors and experimental conditions, and oxidative addition of a single substrate can follow either an inversion or retention pathway, depending on the solvent and concentration, suggesti...

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Stereocontrolled Oxidative Addition of Zerovalent Molybdenum to Enantiomerically Pure Allylic Acetates with Either Inversion or Retention at the Stereogenic Center

Cited by 52 publications

References 35 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

Organometallic Enantiomeric Scaffolding: General Access to 2-Substituted Oxa- and Azabicyclo[3.2.1]octenes via a Brønsted Acid Catalyzed [5 + 2] Cycloaddition Reaction

Mechanistic studies of the molybdenum-catalyzed asymmetric alkylation reaction

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