Enantioselective Syntheses of (+)-Sertraline and (+)-Indatraline Using Lithiation/Borylation–Protodeboronation Methodology

Roesner, Stefan; Mansilla, Javier; Elford, Tim G.; Sonawane, Ravindra P.; Aggarwal, Varinder K.

doi:10.1021/ol202251p

Cited by 98 publications

(43 citation statements)

References 32 publications

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“…Perhaps the hardest challenge is to account for steric effects in complex molecules whereby the entire threedimensional structure may dictate reactivity or its lack (Figure 23 and Ref. [55]). Thes tudy of the influence of steric effects on reaction outcomes dates back to Tafts work on the relative rates of the acid-catalyzed hydrolysis of esters.…”

Section: The Missing Versus Implausible Reaction Suggestions and Postmentioning

confidence: 99%

Computer‐Assisted Synthetic Planning: The End of the Beginning

et al. 2016

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Exactly half a century has passed since the launch of the first documented research project (1965 Dendral) on computer-assisted organic synthesis. Many more programs were created in the 1970s and 1980s but the enthusiasm of these pioneering days had largely dissipated by the 2000s, and the challenge of teaching the computer how to plan organic syntheses earned itself the reputation of a "mission impossible". This is quite curious given that, in the meantime, computers have "learned" many other skills that had been considered exclusive domains of human intellect and creativity-for example, machines can nowadays play chess better than human world champions and they can compose classical music pleasant to the human ear. Although there have been no similar feats in organic synthesis, this Review argues that to concede defeat would be premature. Indeed, bringing together the combination of modern computational power and algorithms from graph/network theory, chemical rules (with full stereo- and regiochemistry) coded in appropriate formats, and the elements of quantum mechanics, the machine can finally be "taught" how to plan syntheses of non-trivial organic molecules in a matter of seconds to minutes. The Review begins with an overview of some basic theoretical concepts essential for the big-data analysis of chemical syntheses. It progresses to the problem of optimizing pathways involving known reactions. It culminates with discussion of algorithms that allow for a completely de novo and fully automated design of syntheses leading to relatively complex targets, including those that have not been made before. Of course, there are still things to be improved, but computers are finally becoming relevant and helpful to the practice of organic-synthetic planning. Paraphrasing Churchill's famous words after the Allies' first major victory over the Axis forces in Africa, it is not the end, it is not even the beginning of the end, but it is the end of the beginning for the computer-assisted synthesis planning. The machine is here to stay.

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Section: The Missing Versus Implausible Reaction Suggestions and Postmentioning

confidence: 99%

Computer‐Assisted Synthetic Planning: The End of the Beginning

et al. 2016

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“…[1e] Thus far, methods for the asymmetric synthesis of chiral b,b-diarylpropionic acids often involve a multistep sequence and/or stoichiometric transformation using chiral auxiliaries, [2] only a few examples of catalytic asymmetric methods, including Rh I -or Cu II -catalyzed reduction of b,b-diaryl unsaturated acrylates [3,4] or nitriles [5] using either polymethylhydrosiloxanes or diethoxymethylsilane as the reductants, and Rh I -catalyzed 1,4-addition of organoboron reagents to arylidene Meldrums acids, [6] have been reported to provide the corresponding b,b-diaryl propanoates or propanenitriles with good to high enantioselectivities. [1e] Thus far, methods for the asymmetric synthesis of chiral b,b-diarylpropionic acids often involve a multistep sequence and/or stoichiometric transformation using chiral auxiliaries, [2] only a few examples of catalytic asymmetric methods, including Rh I -or Cu II -catalyzed reduction of b,b-diaryl unsaturated acrylates [3,4] or nitriles [5] using either polymethylhydrosiloxanes or diethoxymethylsilane as the reductants, and Rh I -catalyzed 1,4-addition of organoboron reagents to arylidene Meldrums acids, [6] have been reported to provide the corresponding b,b-diaryl propanoates or propanenitriles with good to high enantioselectivities.…”

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confidence: 99%

Rhodium(I)‐Catalyzed Enantioselective Hydrogenation of Substituted Acrylic Acids with Sterically Similar β,β‐Diaryls

Li¹,

Dong²,

Wang³

et al. 2013

Angew Chem Int Ed

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Dedicated to Professor Guo-Qiang Lin on the occasion of his 70th birthdayOptically active b,b-diarylpropionic acids are a class of important building blocks for the asymmetric synthesis of chiral diarylmethine compounds, [1] which are structural moieties that are found in many pharmaceuticals and bioactive compounds, including the therapeutically important molecules tolterodine, [1a-b] sertraline, [1c] indatraline, [1d] and natural products, such as cherylline.[1e]Thus far, methods for the asymmetric synthesis of chiral b,b-diarylpropionic acids often involve a multistep sequence and/or stoichiometric transformation using chiral auxiliaries, [2] only a few examples of catalytic asymmetric methods, including Rh I -or Cu II -catalyzed reduction of b,b-diaryl unsaturated acrylates [3,4] or nitriles [5] using either polymethylhydrosiloxanes or diethoxymethylsilane as the reductants, and Rh I -catalyzed 1,4-addition of organoboron reagents to arylidene Meldrums acids, [6] have been reported to provide the corresponding b,b-diaryl propanoates or propanenitriles with good to high enantioselectivities. In terms of atom economy and environmental concerns, asymmetric hydrogenation of b,b-diarylacrylates with molecular H 2 is more advantageous. In this respect, Ir I -or Rh I -catalyzed asymmetric hydrogenation of trisubstituted olefins for the formation of diarylmethine stereogenic centers seems feasible. [7] However, reactions involving 3,3-diarylacrylates (especially free acids) proved to be challenging, as only moderate enantioselectivities were obtained, in most cases under high pressure (100 bar). Herein, we present the results of the development of an efficient asymmetric hydrogenation of b,b-diarylacrylic acids in the presence of a Rh complex based on the heterocombination of a chiral monodentate secondary phosphine oxide (SPO) preligand and an achiral monodentate phosphine ligand as the catalyst to afford a wide variety of the corresponding b,b-diarylpropionic acids with biological importance in excellent optical purities.The most challenging issue associated with the control of stereochemistry in the asymmetric hydrogenation of b,bdiarylacrylic acids is the differentiation of a stereogenic center with two sterically similar aryl groups at the b-position of acrylic acids. [3][4][5][6][7][8] Very recently, we disclosed that Rh I catalysts generated in situ by interaction with SPO preligands demonstrated excellent performance in the asymmetric hydrogenation of a-substituted ethenylphosphonic acids.[9] The salient features of SPO ligands, including ready accessibility, good air and moisture stability, and the potentially H-bonding OH group in the ligand, [9,10] prompted us to explore the catalytic potential of Rh I /SPO systems in the asymmetric hydrogenation of challenging b,b-diarylacrylic acid substrates. As shown in Table 1, chiral monodentate SPO preligands L1-L7 were evaluated in the rhodium-catalyzed asymmetric hydrogenation of (E)-3-phenyl-3-(p-tolyl) acrylic acid ((E)-1 a). However, an initial screening of ...

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“…[15] In the case of propargylic boronic esters, the reaction with tetrabutylammonium fluoride (TBAF) proceeded through a syn-S E ' mechanism [16] to give trisubstituted allenes [17] 6 in excellent yield and enantioselectivity ( Table 3). and with retention of configuration.…”

Section: Methodsmentioning

confidence: 99%

Enantioselective Synthesis and Cross‐Coupling of Tertiary Propargylic Boronic Esters Using Lithiation–Borylation of Propargylic Carbamates

et al. 2012

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Chiral tertiary boronic esters have been shown to be useful intermediates in organic synthesis, as they can undergo a variety of functional group transformations, for example, conversion to alcohols, amines, quaternary centers, or aryldialkylmethines with high stereospecificity. [1] Recently, such intermediates have become available in high ee through two distinct methods: 1) borylation of Michael acceptors [2] or allylic electrophiles, [3] and 2) lithiation-borylation of secondary benzylic carbamates (Scheme 1), [4] which can deliver exceptionally high enantioselectivities over a broad range of substrates (> 99.1 e.r.).

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Enantioselective Syntheses of (+)-Sertraline and (+)-Indatraline Using Lithiation/Borylation–Protodeboronation Methodology

Cited by 98 publications

References 32 publications

Computer‐Assisted Synthetic Planning: The End of the Beginning

Computer‐Assisted Synthetic Planning: The End of the Beginning

Rhodium(I)‐Catalyzed Enantioselective Hydrogenation of Substituted Acrylic Acids with Sterically Similar β,β‐Diaryls

Enantioselective Synthesis and Cross‐Coupling of Tertiary Propargylic Boronic Esters Using Lithiation–Borylation of Propargylic Carbamates

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