Pub Date : 2013-04-19DOI: 10.1002/0471264180.OR080.01
M. Doyle, Yu Liu, M. Ratnikov
The insertion of a chiral-ligated metal carbene into an aliphatic C-H bond to construct a carbon-carbon bond imparts asymmetry into the resultant molecule to form enantiomerically enriched lactones, lactams, and cycloalkane derivatives and returns the chiral-ligated metal to its catalytically active state. Insertion is favored by electron-donating groups adjacent to the C-H bond that undergoes insertion, and is disfavored by electron-withdrawing groups. Chiral dirhodium(II) carboxamidates have proven to have the greatest breadth of high selectivities, but other classes of catalysts are selective in specific cases. Although there are examples of iodonium ylides as reactants, diazo compounds are the reactants of choice for these reactions. Diazocarbonyl compounds, especially diazoacetates and diazoacetamides, have reactivities and selectivities that are most suitable for high product yields and high stereoselectivities. This reaction is optimally designed for the formation of five-membered ring compounds using diazoacetates and diazoacetamides and of four-membered ring products with constrained diazoacetamides. Access to lignan lactones, baclofen, deoxyxylolactone, and rolipram, among others, exemplify the efficiencies of this methodology relative to other synthetic approaches. Keywords: insertion; lactones; lactams; cycloalkanes; diazoesters; diazoketones; catalysts; rhodium; copper; metal carbene; enantioselective; experimental conditions
{"title":"Catalytic, Asymmetric, Intramolecular Carbon–Hydrogen Insertion","authors":"M. Doyle, Yu Liu, M. Ratnikov","doi":"10.1002/0471264180.OR080.01","DOIUrl":"https://doi.org/10.1002/0471264180.OR080.01","url":null,"abstract":"The insertion of a chiral-ligated metal carbene into an aliphatic C-H bond to construct a carbon-carbon bond imparts asymmetry into the resultant molecule to form enantiomerically enriched lactones, lactams, and cycloalkane derivatives and returns the chiral-ligated metal to its catalytically active state. Insertion is favored by electron-donating groups adjacent to the C-H bond that undergoes insertion, and is disfavored by electron-withdrawing groups. Chiral dirhodium(II) carboxamidates have proven to have the greatest breadth of high selectivities, but other classes of catalysts are selective in specific cases. Although there are examples of iodonium ylides as reactants, diazo compounds are the reactants of choice for these reactions. Diazocarbonyl compounds, especially diazoacetates and diazoacetamides, have reactivities and selectivities that are most suitable for high product yields and high stereoselectivities. This reaction is optimally designed for the formation of five-membered ring compounds using diazoacetates and diazoacetamides and of four-membered ring products with constrained diazoacetamides. Access to lignan lactones, baclofen, deoxyxylolactone, and rolipram, among others, exemplify the efficiencies of this methodology relative to other synthetic approaches. \u0000 \u0000 \u0000Keywords: \u0000 \u0000insertion; \u0000lactones; \u0000lactams; \u0000cycloalkanes; \u0000diazoesters; \u0000diazoketones; \u0000catalysts; \u0000rhodium; \u0000copper; \u0000metal carbene; \u0000enantioselective; \u0000experimental conditions","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"35 1","pages":"1-132"},"PeriodicalIF":0.0,"publicationDate":"2013-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88117352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-04-19DOI: 10.1002/0471264180.OR079.01
G. Molander, Ludivine Jean‐Gérard
Organotrifluoroborates are partners for cross-coupling that have emerged as complementary and often unique alternatives to other organoboron reagents. This chapter provides a comprehensive overview of all cross-coupling reactions of the various classes of organotrifluoroborates that have been carried out through August, 2009. The chapter introduces the subject with a discussion of mechanistic considerations concerning the cross-coupling, followed by a brief discussion of the stereochemical aspects of the transformation. The scope and limitations of the reactions are subsequently discussed, first in terms of the organotrifluoroborate and then the electrophilic partner of the reaction. Potential side reactions that are encountered are outlined with useful suggestions on how these can be avoided in practice. Applications in synthesis are described, detailing how organotrifluoroborates have been utilized in the construction of natural products, materials of all types, and pharmacologically active substances. A comparison to other cross-coupling methods rounds out the descriptive part of the chapter. A detailed outline of experimental considerations and protocols has been assembled, gleaning information from the vast array of published procedures to assemble an overview of the most successful conditions. Representative procedures are included for each class of organotrifluoroborate coupling partner, and the tables provide a comprehensive listing of individual reactions. Keywords: organotrifluoroborates; Suzuki-Miyaura cross-coupling; palladium catalysis; nickel catalysis; ligands; biaryl synthesis
{"title":"Cross‐Coupling Reactions of Organotrifluoroborate Salts","authors":"G. Molander, Ludivine Jean‐Gérard","doi":"10.1002/0471264180.OR079.01","DOIUrl":"https://doi.org/10.1002/0471264180.OR079.01","url":null,"abstract":"Organotrifluoroborates are partners for cross-coupling that have emerged as complementary and often unique alternatives to other organoboron reagents. This chapter provides a comprehensive overview of all cross-coupling reactions of the various classes of organotrifluoroborates that have been carried out through August, 2009. \u0000 \u0000 \u0000 \u0000The chapter introduces the subject with a discussion of mechanistic considerations concerning the cross-coupling, followed by a brief discussion of the stereochemical aspects of the transformation. The scope and limitations of the reactions are subsequently discussed, first in terms of the organotrifluoroborate and then the electrophilic partner of the reaction. \u0000 \u0000 \u0000 \u0000Potential side reactions that are encountered are outlined with useful suggestions on how these can be avoided in practice. Applications in synthesis are described, detailing how organotrifluoroborates have been utilized in the construction of natural products, materials of all types, and pharmacologically active substances. A comparison to other cross-coupling methods rounds out the descriptive part of the chapter. \u0000 \u0000 \u0000 \u0000A detailed outline of experimental considerations and protocols has been assembled, gleaning information from the vast array of published procedures to assemble an overview of the most successful conditions. Representative procedures are included for each class of organotrifluoroborate coupling partner, and the tables provide a comprehensive listing of individual reactions. \u0000 \u0000 \u0000Keywords: \u0000 \u0000organotrifluoroborates; \u0000Suzuki-Miyaura cross-coupling; \u0000palladium catalysis; \u0000nickel catalysis; \u0000ligands; \u0000biaryl synthesis","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"150 1","pages":"1-316"},"PeriodicalIF":0.0,"publicationDate":"2013-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75951274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-10-31DOI: 10.1002/0471264180.OR078.03
L. Guziec, F. S. Guziec
Twofold extrusion reactions are chemical transformations in which two small inorganic molecules or atoms connecting carbon or nitrogen atoms are lost, generating the corresponding carbon-carbon or carbon-nitrogen double bonds. These reactions are particularly useful for the preparation of sterically hindered alkenes and imines. The inorganic species liberated in twofold extrusion reactions can be molecular nitrogen, sulfur, selenium, tellurium, sulfur dioxide, sulfur monoxide, carbon dioxide or carbon monoxide. The most common precursors for twofold extrusion reactions are 1,3,4-thiadiazolines, which thermally extrude molecular nitrogen affording thiiranes. These thiiranes can be readily desulfurized to afford the corresponding alkenes using tertiary phosphines. The corresponding 1,3,4-selenadiazolines thermally extrude both molecular nitrogen and atomic selenium directly affording alkenes. Alkenes can also be prepared by formal extrusions of molecular nitrogen plus sulfur dioxide or sulfur monoxide. Extremely sterically hindered imines can be prepared by extrusions of molecular nitrogen and sulfur or selenium from in situ generated heterocyclic precursors. Other less common twofold extrusion reactions are also reported. The detailed preparations of the required precursors for the twofold extrusion reactions as well as the mechanisms of these extrusion processes are discussed in this chapter. The utility of twofold extrusion reactions in the preparations of ‘molecular rotors’ and other extremely sterically hindered alkenes is presented. The steric limitations of the twofold extrusion reactions are discussed along with comparisons of these reactions with other alkene- and imine-forming synthetic methods. The Tabular Survey covers material through the end of 2009. Keywords: Extrusion; twofold extrusion; alkene; imine; 1,3,4-thiadiazolines; 1,3,4-selenadiazolines; [nitrogen, sulfur, selenium, tellurium, sulfur dioxide, sulfur monoxide, carbon dioxide and carbon monoxide (all with extrusion)]; thiocarbonyl ylide; tertiary phosphine; diazo compounds; thiones; selones; sulfenes; selenirane; azines; chelotropic extrusion; Barton-Kellogg reaction; Staudinger-Pfenninger reaction; Schonberg reaction; thiadiazoline-1,1-dioxides; thiirane 1,1-dioxide; thiirane 1-oxide; oxathiolan-4-ones; lead tetraacetate; barium manganate; diselenium dibromide; thiocarbonyl-S-imide; copper powder; photochemical extrusion; flash vacuum pyrolysis (FVP); rhodium (II) acetate; 1,3-dithiacyclopentanes; hydrazones; thiaziridine 1,1-dioxides; p-toluenesulfonylhydrazones; 1,2,3-thiadiazolines; alkenes (sterically hindered); imines (sterically hindered); N-sulfonylamines; retrocyclization; iminium salts (sterically hindered); geminal dihalides; nanoscale devices; photonic devices; thiophosgene; O-thioesters; O-selenoesters; enol ethers; dithioesters; thioenol ethers; thionolactones; thioamides; thiolactams; t
{"title":"Twofold Extrusion Reactions","authors":"L. Guziec, F. S. Guziec","doi":"10.1002/0471264180.OR078.03","DOIUrl":"https://doi.org/10.1002/0471264180.OR078.03","url":null,"abstract":"Twofold extrusion reactions are chemical transformations in which two small inorganic molecules or atoms connecting carbon or nitrogen atoms are lost, generating the corresponding carbon-carbon or carbon-nitrogen double bonds. These reactions are particularly useful for the preparation of sterically hindered alkenes and imines. The inorganic species liberated in twofold extrusion reactions can be molecular nitrogen, sulfur, selenium, tellurium, sulfur dioxide, sulfur monoxide, carbon dioxide or carbon monoxide. \u0000 \u0000 \u0000 \u0000The most common precursors for twofold extrusion reactions are 1,3,4-thiadiazolines, which thermally extrude molecular nitrogen affording thiiranes. These thiiranes can be readily desulfurized to afford the corresponding alkenes using tertiary phosphines. The corresponding 1,3,4-selenadiazolines thermally extrude both molecular nitrogen and atomic selenium directly affording alkenes. Alkenes can also be prepared by formal extrusions of molecular nitrogen plus sulfur dioxide or sulfur monoxide. Extremely sterically hindered imines can be prepared by extrusions of molecular nitrogen and sulfur or selenium from in situ generated heterocyclic precursors. Other less common twofold extrusion reactions are also reported. \u0000 \u0000 \u0000 \u0000The detailed preparations of the required precursors for the twofold extrusion reactions as well as the mechanisms of these extrusion processes are discussed in this chapter. The utility of twofold extrusion reactions in the preparations of ‘molecular rotors’ and other extremely sterically hindered alkenes is presented. The steric limitations of the twofold extrusion reactions are discussed along with comparisons of these reactions with other alkene- and imine-forming synthetic methods. The Tabular Survey covers material through the end of 2009. \u0000 \u0000 \u0000Keywords: \u0000 \u0000Extrusion; \u0000twofold extrusion; \u0000alkene; \u0000imine; \u00001,3,4-thiadiazolines; \u00001,3,4-selenadiazolines; \u0000[nitrogen, sulfur, selenium, tellurium, sulfur dioxide, sulfur monoxide, carbon dioxide and carbon monoxide (all with extrusion)]; \u0000thiocarbonyl ylide; \u0000tertiary phosphine; \u0000diazo compounds; \u0000thiones; \u0000selones; \u0000sulfenes; \u0000selenirane; \u0000azines; \u0000chelotropic extrusion; \u0000Barton-Kellogg reaction; \u0000Staudinger-Pfenninger reaction; \u0000Schonberg reaction; \u0000thiadiazoline-1,1-dioxides; \u0000thiirane 1,1-dioxide; \u0000thiirane 1-oxide; \u0000oxathiolan-4-ones; \u0000lead tetraacetate; \u0000barium manganate; \u0000diselenium dibromide; \u0000thiocarbonyl-S-imide; \u0000copper powder; \u0000photochemical extrusion; \u0000flash vacuum pyrolysis (FVP); \u0000rhodium (II) acetate; \u00001,3-dithiacyclopentanes; \u0000hydrazones; \u0000thiaziridine 1,1-dioxides; \u0000p-toluenesulfonylhydrazones; \u00001,2,3-thiadiazolines; \u0000alkenes (sterically hindered); \u0000imines (sterically hindered); \u0000N-sulfonylamines; \u0000retrocyclization; \u0000iminium salts (sterically hindered); \u0000geminal dihalides; \u0000nanoscale devices; \u0000photonic devices; \u0000thiophosgene; \u0000O-thioesters; \u0000O-selenoesters; \u0000enol ethers; \u0000dithioesters; \u0000thioenol ethers; \u0000thionolactones; \u0000thioamides; \u0000thiolactams; \u0000t","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"24 1","pages":"411-550"},"PeriodicalIF":0.0,"publicationDate":"2012-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74963302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-07-13DOI: 10.1002/0471264180.OR077.02
S. McCombie, W. Motherwell, M. Tozer
Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site-specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon-centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C-O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high-yielding way to realize this sequence was first described by Barton McCombie using the free-radical chain reaction of O-thioacyl derivatives of secondary alcohols with tri-n-butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products. Keywords: Barton-McCombie reaction; Deoxygenation; Thioacylation; Alcohols; Reduction; Tri-n-butylstannane; O-Thioacyl derivatives; Reagents; Mechanism; Method comparisons; Experimental procedures
{"title":"The Barton-McCombie Reaction","authors":"S. McCombie, W. Motherwell, M. Tozer","doi":"10.1002/0471264180.OR077.02","DOIUrl":"https://doi.org/10.1002/0471264180.OR077.02","url":null,"abstract":"Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site-specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon-centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C-O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high-yielding way to realize this sequence was first described by Barton McCombie using the free-radical chain reaction of O-thioacyl derivatives of secondary alcohols with tri-n-butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products. \u0000 \u0000 \u0000Keywords: \u0000 \u0000Barton-McCombie reaction; \u0000Deoxygenation; \u0000Thioacylation; \u0000Alcohols; \u0000Reduction; \u0000Tri-n-butylstannane; \u0000O-Thioacyl derivatives; \u0000Reagents; \u0000Mechanism; \u0000Method comparisons; \u0000Experimental procedures","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"1 1","pages":"161-432"},"PeriodicalIF":0.0,"publicationDate":"2012-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81549792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-07-13DOI: 10.1002/0471264180.OR077.01
J. Cha, O. Kulinkovich
Cyclopropanes are characterized by high ring-strain energy and have been employed as useful building blocks in organic synthesis. The incorporation of a heteroatom donor substituent such as OH, OR, NR2, or SR on the ring imparts enhanced reactivity. Hydroxycyclopropanes (cyclopropanols) in particular have been thoroughly studied due to their facile ring cleavage. Among several known methods, a new method for preparation of cyclopropanols involves dialkoxytitanacyclopropane-mediated cyclopropanation (the Kulinkovich cyclopropanation) of esters with Grignard reagent in the presence of titanium isopropoxide. The striking feature of this method is the facile formation of a three-membered ring from a simple Grignard reagent which acts as a 1,2-dicarbanion equivalent through a pivotal dialkoxytitana-cycloproapne intermediate. These reactions benefit from the availability of inexpensive reagents, ease of operation, and high selectivity for cis-dialkylcyclopropanols. This cyclopropanation reaction has since been extended to other carboxylic derivatives to provide convenient access to several heteroatom-substituted cyclopropanes. The objective of this chapter is to provide an updated, comprehensive coverage of the literature on the Kulinkovich cyclopropanation reaction and related processes. Key mechanistic issues are summarized. Keywords: Kulinkovich cyclopropanation; Carboxylic acid derivatives; Grignard reagents; Titanium alkoxides; Cyclopropanol; Carbonyl compounds; Mechanisms; Esters; Aminocyclopropanes; Imides; Experimental procedures; Comparison of methods
{"title":"The Kulinkovich Cyclopropanation of Carboxylic Acid Derivatives","authors":"J. Cha, O. Kulinkovich","doi":"10.1002/0471264180.OR077.01","DOIUrl":"https://doi.org/10.1002/0471264180.OR077.01","url":null,"abstract":"Cyclopropanes are characterized by high ring-strain energy and have been employed as useful building blocks in organic synthesis. The incorporation of a heteroatom donor substituent such as OH, OR, NR2, or SR on the ring imparts enhanced reactivity. Hydroxycyclopropanes (cyclopropanols) in particular have been thoroughly studied due to their facile ring cleavage. Among several known methods, a new method for preparation of cyclopropanols involves dialkoxytitanacyclopropane-mediated cyclopropanation (the Kulinkovich cyclopropanation) of esters with Grignard reagent in the presence of titanium isopropoxide. The striking feature of this method is the facile formation of a three-membered ring from a simple Grignard reagent which acts as a 1,2-dicarbanion equivalent through a pivotal dialkoxytitana-cycloproapne intermediate. These reactions benefit from the availability of inexpensive reagents, ease of operation, and high selectivity for cis-dialkylcyclopropanols. This cyclopropanation reaction has since been extended to other carboxylic derivatives to provide convenient access to several heteroatom-substituted cyclopropanes. The objective of this chapter is to provide an updated, comprehensive coverage of the literature on the Kulinkovich cyclopropanation reaction and related processes. Key mechanistic issues are summarized. \u0000 \u0000 \u0000Keywords: \u0000 \u0000Kulinkovich cyclopropanation; \u0000Carboxylic acid derivatives; \u0000Grignard reagents; \u0000Titanium alkoxides; \u0000Cyclopropanol; \u0000Carbonyl compounds; \u0000Mechanisms; \u0000Esters; \u0000Aminocyclopropanes; \u0000Imides; \u0000Experimental procedures; \u0000Comparison of methods","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"1 1","pages":"1-160"},"PeriodicalIF":0.0,"publicationDate":"2012-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90113718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-03-14DOI: 10.1002/0471264180.OR076.01
T. Donohoe, C. Bataille, P. Innocenti
This chapter focuses on the dihydroxylation of alkenes using osmium tetraoxide that is directed by alcohols and amine derivatives through hydrogen bonding between the substrate and the oxidant. Discussion focuses on the different types of directing groups that are viable. The outcome from directed dehydroxylation of all the major classes of alkenes, including cyclic and acyclic substrates and varied alkene substration patterns, is also addressed. The mechanism section outlines the different reactivity patterns that various ligands can impart onto the osmium oxides together with the importance of chosing a solvent that encourages hydrogen bonding. The influence that the directing group has on syn selectivity is also discussed, in both the context of its position in space and with respect to the alkane, and the relationship between the PKa of the acidic proton and syn selectivity. Osmium tetraoxide has established itself as the reagent of choice for the syn-dihydroxylation of olefins, primarily because of its inertness towards other functional groups and lack of over-oxidation products. Information on research in regard to dihydroxylation is given. Only a few other synthetic methods are known that accomplish the direct addition of a diol unit across an alkene while controlling the stereochemical course of the process. The Woodward modification of the Prevost reaction (adds two oxygen atoms in a syn fashion across an alkane) is discussed in detail in the comparison of methods section. Keywords: Dihydroxylation; Osmium tetroxide; Mechanisms; Site selectivity; Conformational factors; Hydrogen bonding; Directing group; Amines; Alcohols; Steric effects; Method comparisons; Sodium sulfite; Acidic methanol; Ethylenediamine; Experimental procedures
{"title":"Hydrogen‐Bonding‐Mediated Directed Osmium Dihydroxylation","authors":"T. Donohoe, C. Bataille, P. Innocenti","doi":"10.1002/0471264180.OR076.01","DOIUrl":"https://doi.org/10.1002/0471264180.OR076.01","url":null,"abstract":"This chapter focuses on the dihydroxylation of alkenes using osmium tetraoxide that is directed by alcohols and amine derivatives through hydrogen bonding between the substrate and the oxidant. Discussion focuses on the different types of directing groups that are viable. The outcome from directed dehydroxylation of all the major classes of alkenes, including cyclic and acyclic substrates and varied alkene substration patterns, is also addressed. The mechanism section outlines the different reactivity patterns that various ligands can impart onto the osmium oxides together with the importance of chosing a solvent that encourages hydrogen bonding. The influence that the directing group has on syn selectivity is also discussed, in both the context of its position in space and with respect to the alkane, and the relationship between the PKa of the acidic proton and syn selectivity. Osmium tetraoxide has established itself as the reagent of choice for the syn-dihydroxylation of olefins, primarily because of its inertness towards other functional groups and lack of over-oxidation products. Information on research in regard to dihydroxylation is given. Only a few other synthetic methods are known that accomplish the direct addition of a diol unit across an alkene while controlling the stereochemical course of the process. The Woodward modification of the Prevost reaction (adds two oxygen atoms in a syn fashion across an alkane) is discussed in detail in the comparison of methods section. \u0000 \u0000 \u0000Keywords: \u0000 \u0000Dihydroxylation; \u0000Osmium tetroxide; \u0000Mechanisms; \u0000Site selectivity; \u0000Conformational factors; \u0000Hydrogen bonding; \u0000Directing group; \u0000Amines; \u0000Alcohols; \u0000Steric effects; \u0000Method comparisons; \u0000Sodium sulfite; \u0000Acidic methanol; \u0000Ethylenediamine; \u0000Experimental procedures","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"49 1","pages":"1-48"},"PeriodicalIF":0.0,"publicationDate":"2012-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84704124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-03-14DOI: 10.1002/0471264180.OR076.03
S. Cacchi*, G. Fabrizi, A. Goggiamani
The palladium-catalyzed assembly of the functionalized pyrrole nucleus on a benzenoid scaffold is a widley used synthetic tool for the preparation of indole derivatives. This construction can be categorized into four main types: (1) cyclization of alkynes; (2) cyclization of alkenes; (3) cyclization via C-vinyl reactions; and (4) cyclization via N − arylation or N − vinylation reactions. The first approach is the most versatile in terms of range of the added functional groups and of the bonds that can be created in the construction of the pyrrole ring. This method is based on the utilization of precursors containing nitrogen nucleophiles and carbon-carbon triple bonds. The nitrogen nucleophile and alkyne moiety may be part of the same molecule or belong to two different molecules. Some of the most general cyclizations of indoles are summarized. Alkene-based cyclizations to give indoles are also summarized. Cyclization to indoles via arene vinylation has limited synthetic scope. Indoles can be prepared via cyclizations proceeding through N-arylation and N-vinylation reactions based on pioneering work. In general, only synthetic procedures where palladium catalysis is involved in the pryrrole ring construction event are discussed in this chapter. Keywords: Indoles; Palladium catalysts; Pyrroles; Cyclization; Vinylation; Alkenes; Alkynes; Copper; Catalysts; Substituted indoles; Mechanisms; Method comparisons; Experimental procedures
钯催化的功能化吡咯核在苯类支架上的组装是一种广泛使用的合成工具，用于制备吲哚衍生物。这种结构可分为四种主要类型:(1)炔烃环化;(2)烯烃的环化;(3) c -乙烯基环化反应;(4)通过N -芳基化或N -乙烯基化反应进行环化。第一种方法在添加官能团的范围和在构建吡咯环时可以创建的键的范围方面是最通用的。这种方法是基于利用含有氮亲核试剂和碳碳三键的前驱体。氮亲核试剂和炔部分可能是同一分子的一部分，也可能属于两个不同的分子。总结了吲哚的一些最普遍的环化。还总结了烯烃环化生成吲哚的方法。芳烃乙烯化合成吲哚的合成范围有限。吲哚可以通过n -芳基化和n -乙烯基化反应进行环化制备。一般来说，本章只讨论钯催化参与吡咯环构建事件的合成过程。关键词:吲哚;钯催化剂;吡咯;环化;乙烯化作用;烯烃;炔烃;铜;催化剂;取代吲哚;机制;方法比较;实验程序
{"title":"Indoles via Palladium‐Catalyzed Cyclization","authors":"S. Cacchi*, G. Fabrizi, A. Goggiamani","doi":"10.1002/0471264180.OR076.03","DOIUrl":"https://doi.org/10.1002/0471264180.OR076.03","url":null,"abstract":"The palladium-catalyzed assembly of the functionalized pyrrole nucleus on a benzenoid scaffold is a widley used synthetic tool for the preparation of indole derivatives. This construction can be categorized into four main types: (1) cyclization of alkynes; (2) cyclization of alkenes; (3) cyclization via C-vinyl reactions; and (4) cyclization via N − arylation or N − vinylation reactions. The first approach is the most versatile in terms of range of the added functional groups and of the bonds that can be created in the construction of the pyrrole ring. This method is based on the utilization of precursors containing nitrogen nucleophiles and carbon-carbon triple bonds. The nitrogen nucleophile and alkyne moiety may be part of the same molecule or belong to two different molecules. Some of the most general cyclizations of indoles are summarized. Alkene-based cyclizations to give indoles are also summarized. Cyclization to indoles via arene vinylation has limited synthetic scope. Indoles can be prepared via cyclizations proceeding through N-arylation and N-vinylation reactions based on pioneering work. In general, only synthetic procedures where palladium catalysis is involved in the pryrrole ring construction event are discussed in this chapter. \u0000 \u0000 \u0000Keywords: \u0000 \u0000Indoles; \u0000Palladium catalysts; \u0000Pyrroles; \u0000Cyclization; \u0000Vinylation; \u0000Alkenes; \u0000Alkynes; \u0000Copper; \u0000Catalysts; \u0000Substituted indoles; \u0000Mechanisms; \u0000Method comparisons; \u0000Experimental procedures","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"20 1","pages":"281-534"},"PeriodicalIF":0.0,"publicationDate":"2012-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87075908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-03-14DOI: 10.1002/0471264180.OR076.02
D. Prim, S. Marque, A. Gaucher, J. Campagne
The aim of this chapter is to present an up-to-date overview of the transition-metal-catalyzed alpha-arylation of enolates and their derivatives. This chapter discusses the various efforts to develop highly efficient and selective tools for the catalyzed formation of carbon-carbon and carbon-heteroatom bonds. Among the latter, outstanding results have been obtained in the field of soft, non-organometallic nucleophiles. One of the major challenges is the alpha-arylation of soft carbon nucelophiles such as stabilized carbon enolates and related functional groups. Although alpha-carboxylic acids and keto derivatives are prevalent in natural products and are important in the building blocks of various drugs (e.g., anti-inflammatory drugs, anesthetics, etc.), catalytic alpha-arylation of stabilized carbon enolates has only been recently described. Details on early research is given. More recent developments of this method concern not only the use of a large number of related nucleophiles, but also activated benzylic and vinylogous gamma-arylations. Current efforts are mainly devoted to multiple arylation sequences, intramolecular alpha-arylations, and enantioselective alpha-arylation. Because palladium is the transition metal predominantly employed, the chapter focuses on palladium-assisted synthetic transformation, However other catalytic systems such as nickel, copper, and ruthenium-based catalysts are detailed. Keywords: Alpha-arylation; Enolates; Transition metal; Catalysts; Palladium; Copper; Nickel; Ketones Aldehydes; Amides; Esters; Amino acids; Nitriles; Methylene compounds; Mechanisms; Comparison methods; Experimental procedures
{"title":"Transition‐Metal‐Catalyzed α‐Arylation of Enolates","authors":"D. Prim, S. Marque, A. Gaucher, J. Campagne","doi":"10.1002/0471264180.OR076.02","DOIUrl":"https://doi.org/10.1002/0471264180.OR076.02","url":null,"abstract":"The aim of this chapter is to present an up-to-date overview of the transition-metal-catalyzed alpha-arylation of enolates and their derivatives. This chapter discusses the various efforts to develop highly efficient and selective tools for the catalyzed formation of carbon-carbon and carbon-heteroatom bonds. Among the latter, outstanding results have been obtained in the field of soft, non-organometallic nucleophiles. One of the major challenges is the alpha-arylation of soft carbon nucelophiles such as stabilized carbon enolates and related functional groups. Although alpha-carboxylic acids and keto derivatives are prevalent in natural products and are important in the building blocks of various drugs (e.g., anti-inflammatory drugs, anesthetics, etc.), catalytic alpha-arylation of stabilized carbon enolates has only been recently described. Details on early research is given. More recent developments of this method concern not only the use of a large number of related nucleophiles, but also activated benzylic and vinylogous gamma-arylations. Current efforts are mainly devoted to multiple arylation sequences, intramolecular alpha-arylations, and enantioselective alpha-arylation. Because palladium is the transition metal predominantly employed, the chapter focuses on palladium-assisted synthetic transformation, However other catalytic systems such as nickel, copper, and ruthenium-based catalysts are detailed. \u0000 \u0000 \u0000Keywords: \u0000 \u0000Alpha-arylation; \u0000Enolates; \u0000Transition metal; \u0000Catalysts; \u0000Palladium; \u0000Copper; \u0000Nickel; \u0000Ketones Aldehydes; \u0000Amides; \u0000Esters; \u0000Amino acids; \u0000Nitriles; \u0000Methylene compounds; \u0000Mechanisms; \u0000Comparison methods; \u0000Experimental procedures","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"1 1","pages":"49-280"},"PeriodicalIF":0.0,"publicationDate":"2012-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85563468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-12-16DOI: 10.1002/0471264180.OR075.02
H. Davies, Phillip M. Pelphrey
The metal-catalyzed reactions of diazo compounds have broad utility in organic synthesis. The resulting high-energy metal carbenoid intermediates are capable of a range of useful transformations, including cyclopropanation, ylide formation, and C-H insertion. The intermolecular C-H insertion by metal carbenoids is the most versatile reaction to date for stereoselective C-H functionalization. This chapter covers the historical background of C-H insertions and describes how the utilization of new catalysts and more stabilized carbenoids has resulted in major advances in the field. Now that highly diastereoselective and enantioselective C-H functionalization can be achieved, the method can be effectively applied to the synthesis of pharmaceutical agents and natural products. This chapter focuses exclusively on intermolecular C-H insertions of metal carbenoids in sp3-hybridized C-H bonds. The carbenoids can be classified into three major classes: 1, acceptor-substituted carbenoids; 2, acceptor/acceptor-substituted carbenoids; and 3, donor/acceptor-substituted carbenoids Keywords: Intermolecular C-H insertions; Carbenoids; Hydrocarbons; Activated C-H bonds; Site selectivity; Donors; Acceptors; Aryldiazoacetates; Metal catalysts; Experimental procedures; Mechanisms
{"title":"Intermolecular C–H Insertions of Carbenoids","authors":"H. Davies, Phillip M. Pelphrey","doi":"10.1002/0471264180.OR075.02","DOIUrl":"https://doi.org/10.1002/0471264180.OR075.02","url":null,"abstract":"The metal-catalyzed reactions of diazo compounds have broad utility in organic synthesis. The resulting high-energy metal carbenoid intermediates are capable of a range of useful transformations, including cyclopropanation, ylide formation, and C-H insertion. \u0000 \u0000 \u0000 \u0000The intermolecular C-H insertion by metal carbenoids is the most versatile reaction to date for stereoselective C-H functionalization. This chapter covers the historical background of C-H insertions and describes how the utilization of new catalysts and more stabilized carbenoids has resulted in major advances in the field. Now that highly diastereoselective and enantioselective C-H functionalization can be achieved, the method can be effectively applied to the synthesis of pharmaceutical agents and natural products. This chapter focuses exclusively on intermolecular C-H insertions of metal carbenoids in sp3-hybridized C-H bonds. The carbenoids can be classified into three major classes: 1, acceptor-substituted carbenoids; 2, acceptor/acceptor-substituted carbenoids; and 3, donor/acceptor-substituted carbenoids \u0000 \u0000 \u0000Keywords: \u0000 \u0000Intermolecular C-H insertions; \u0000Carbenoids; \u0000Hydrocarbons; \u0000Activated C-H bonds; \u0000Site selectivity; \u0000Donors; \u0000Acceptors; \u0000Aryldiazoacetates; \u0000Metal catalysts; \u0000Experimental procedures; \u0000Mechanisms","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"95 1","pages":"75-212"},"PeriodicalIF":0.0,"publicationDate":"2011-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85259799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-12-16DOI: 10.1002/0471264180.OR075.04
L. Overman, P. Humphreys, G. Welmaker
Because of their ability to rapidly build molecular complexity, reactions that construct several carbon-carbon bonds are of special value in organic synthesis. Among these transformations, cascade reactions form several bonds by an orchestrated sequence in which the first bond-forming step reveals functionality that allows subsequent bond forming transformations. In 1979 such a sequence for the synthesis of 3-acylpyrrolidines and azacyclic structures that contain this unit was reported. This reaction is now commonly called the aza-Cope/Mannich reaction, a [3,3]-sigmatropic rearrangement of an unsaturated iminium cation generates the iminium ion and enol that are participants in a subsequent intramolecular Mannich reaction. The aza-Cope/Mannich reaction has not been the subject of comprehensive review. This chapter covers the common version of the transformation discussed above along with the formation of 3-acylpyrrolidines by a related base-promoted cascade sequence. Keywords: Aza-Cope/Mannich reactions; 1- Aminobut-3-en-2-ols; Amine alkylation; Iminium ion; Vinyl substituents; Stereochemistry; Mechanisms; Condensation; Solvent; Acid; Ring enlarging; Rearrangements; Base-promoted reactions; Experimental procedures
{"title":"The Aza‐Cope/Mannich Reaction","authors":"L. Overman, P. Humphreys, G. Welmaker","doi":"10.1002/0471264180.OR075.04","DOIUrl":"https://doi.org/10.1002/0471264180.OR075.04","url":null,"abstract":"Because of their ability to rapidly build molecular complexity, reactions that construct several carbon-carbon bonds are of special value in organic synthesis. Among these transformations, cascade reactions form several bonds by an orchestrated sequence in which the first bond-forming step reveals functionality that allows subsequent bond forming transformations. In 1979 such a sequence for the synthesis of 3-acylpyrrolidines and azacyclic structures that contain this unit was reported. This reaction is now commonly called the aza-Cope/Mannich reaction, a [3,3]-sigmatropic rearrangement of an unsaturated iminium cation generates the iminium ion and enol that are participants in a subsequent intramolecular Mannich reaction. \u0000 \u0000 \u0000 \u0000The aza-Cope/Mannich reaction has not been the subject of comprehensive review. This chapter covers the common version of the transformation discussed above along with the formation of 3-acylpyrrolidines by a related base-promoted cascade sequence. \u0000 \u0000 \u0000Keywords: \u0000 \u0000Aza-Cope/Mannich reactions; \u00001- Aminobut-3-en-2-ols; \u0000Amine alkylation; \u0000Iminium ion; \u0000Vinyl substituents; \u0000Stereochemistry; \u0000Mechanisms; \u0000Condensation; \u0000Solvent; \u0000Acid; \u0000Ring enlarging; \u0000Rearrangements; \u0000Base-promoted reactions; \u0000Experimental procedures","PeriodicalId":19539,"journal":{"name":"Organic Reactions","volume":"15 1","pages":"747-820"},"PeriodicalIF":0.0,"publicationDate":"2011-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80439627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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