Homobenzotetramisole:  An Effective Catalyst for Kinetic Resolution of Aryl-Cycloalkanols

Birman, Vladimir B.; Li, Ximin

doi:10.1021/ol703119n

Cited by 199 publications

(118 citation statements)

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“…The efficacy of these catalysts has been demonstrated in the acylative kinetic resolution of secondary alcohols, [62] oxazolidinones, [63] and lactams (Scheme 18A). [64] These catalysts have also been employed for dynamic kinetic resolution (DKR) of azlactones en route to natural and unnatural α-amino esters (Scheme 18B).…”

Section: Catalyst–substrate Cation–π Interactionsmentioning

confidence: 99%

“…Fossey and coworkers subsequently combined insights from work by Fu [36] and Birman [62],[66] to develop a ferrocene-based amidine catalyst ( 72 ) containing elements of planar and central chirality for the acylative kinetic resolution of secondary benzylic alcohols (Scheme 19). [68] The stereoselectivity observed with this catalyst system is dependent on the matched arrangement of the pentaphenyl ferrocene floor and a second α-aryl appendage to shield the bottom face of the catalyst.…”

Section: Catalyst–substrate Cation–π Interactionsmentioning

confidence: 99%

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The Cation–π Interaction in Small‐Molecule Catalysis

2016

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Catalysis by small molecules (≤ 1000 Da, 10−9 m) capable of binding and activating substrates via attractive, noncovalent interactions has emerged as an important approach in organic and organometallic chemistry. While the canonical noncovalent interactions—including hydrogen-bonding, ion-pairing, and π-stacking—have become mainstays of catalyst design, the cation–π interaction has been comparatively underutilized in this context since its discovery in the 1980s. However, like a hydrogen bond, the cation–π interaction exhibits a typical binding affinity of several kcal/mol with substantial directionality. These properties render it attractive as a design element for the development of small-molecule catalysts, and in recent years, the catalysis community has begun to take advantage of these features, drawing inspiration from pioneering research in molecular recognition and structural biology. This review surveys the burgeoning application of the cation–π interaction in catalysis.

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Section: Catalyst–substrate Cation–π Interactionsmentioning

confidence: 99%

Section: Catalyst–substrate Cation–π Interactionsmentioning

confidence: 99%

The Cation–π Interaction in Small‐Molecule Catalysis

2016

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“…This type of cascade process, which generates multiple C À C and C À X bonds and stereogenic centers, including quaternary carbon atoms, is highly useful in chemical biology, [1] for example when attempting to synthesize a family of compounds around a natural product lead. We developed intramolecular nucleophile-catalyzed aldol lactonization (NCAL) processes that deliver bicyclic b-lactones [2] from aldehyde acid substrates by using Cinchona alkaloid catalysts and modified Mukaiyama activating agents.[3] The NCAL methodology was more recently applied to keto acid substrates by using stoichiometric nucleophiles including 4-pyrrolidinopyridine (4-PPY), which led to a variety of racemic bi-and tricyclic b-lactones, [4] and a nine-step enantioselective synthesis of salinosporamide A from d-serine.[5]Tricyclic-b-lactones (AE )-4 (Scheme 1) were also found to participate in a novel dyotropic process leading to spirocyclic g-lactones.[6] In the latter report, we described a single example of an enantioselective NCAL process with keto acids leading to b-lactone (À)-4, by employing stoichiometric quantities of commercially available tetramisole (Scheme 1).[7]Herein, we report a significant advance in the NCAL methodology with keto acids involving the use of catalytic homobenzotetramisole (S)-HBTM [8] (6, Scheme 2) as chiral nucleophile (Lewis base), a tetramisole analogue, and p-toluenesulfonyl chloride rather than Mukaiyamas reagent, which led to bi-and tricyclic b-lactones in good yields and excellent enantioselectivities. In addition, we report transformations of these systems that lead to dramatically different topologies.…”

mentioning

confidence: 99%

Enantioselective, Organocatalyzed, Intramolecular Aldol Lactonizations with Keto Acids Leading to Bi‐ and Tricyclic β‐Lactones and Topology‐Morphing Transformations

2010

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The ability to rapidly assemble complex carbocyclic frameworks in a catalytic, asymmetric manner has garnered great interest in recent years. This type of cascade process, which generates multiple C À C and C À X bonds and stereogenic centers, including quaternary carbon atoms, is highly useful in chemical biology, [1] for example when attempting to synthesize a family of compounds around a natural product lead. We developed intramolecular nucleophile-catalyzed aldol lactonization (NCAL) processes that deliver bicyclic b-lactones [2] from aldehyde acid substrates by using Cinchona alkaloid catalysts and modified Mukaiyama activating agents.[3] The NCAL methodology was more recently applied to keto acid substrates by using stoichiometric nucleophiles including 4-pyrrolidinopyridine (4-PPY), which led to a variety of racemic bi-and tricyclic b-lactones, [4] and a nine-step enantioselective synthesis of salinosporamide A from d-serine.[5]Tricyclic-b-lactones (AE )-4 (Scheme 1) were also found to participate in a novel dyotropic process leading to spirocyclic g-lactones.[6] In the latter report, we described a single example of an enantioselective NCAL process with keto acids leading to b-lactone (À)-4, by employing stoichiometric quantities of commercially available tetramisole (Scheme 1).[7]Herein, we report a significant advance in the NCAL methodology with keto acids involving the use of catalytic homobenzotetramisole (S)-HBTM [8] (6, Scheme 2) as chiral nucleophile (Lewis base), a tetramisole analogue, and p-toluenesulfonyl chloride rather than Mukaiyamas reagent, which led to bi-and tricyclic b-lactones in good yields and excellent enantioselectivities. In addition, we report transformations of these systems that lead to dramatically different topologies. Overall, the reported process provides an expedient route to useful templates for chemical biology through rapid synthesis of carbocyclic frameworks in optically active form. The resident b-lactone is also a versatile handle for further manipulations. Furthermore, the described methodology is the first example of catalytic desymmetrization reactions of cyclic diones by the NCAL process.To develop a catalytic NCAL process for keto acid substrates premised on our working mechanistic hypothesis, [4] we considered the use of more electron rich nucleophiles (Lewis bases). We postulated that this could lead to increased concentrations of intermediate aldolates, which in turn would increase the rate of the final, presumed rate-limiting ring closure to b-lactone. With this hypothesis in mind and building on initial success with stoichiometric (À)-tetramisole Scheme 1. Previous racemic and stoichiometric enantioselective NCAL variants leading to bi-and tricyclic b-lactones, and the described practical, catalytic, asymmetric NCAL process. Tf = trifluoromethanesulfonyl, Ts = toluenesulfonyl.Scheme 2. Birman's chiral cyclic isothiourea catalysts screened in the NCAL process.

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“…65 Good enantioselectivities were achieved for substrates with aromatic moieties, whereas the S-values decreased for substrates containing an -N 3 or -OBz group in the 2-position of the alkyl ring (Table 18). 65 In 2007 Shiina and Nakata reported the KR of secondary benzylic alcohols mediated by catalyst 130. 66 In contrast to Birman's approach, where anhydrides were used as acyl source, Shiina used carboxylic acids as the acylation agents.…”

Section: Omementioning

confidence: 99%