Academic literature on the topic 'Alkyl-Aryl couplings'

Aryl benzoates are compounds of high importance in organic synthesis. Herein, we report the iron-catalyzed C(sp2)–C(sp3) Kumada cross-coupling of aryl chlorobenzoates with alkyl Grignard reagents. The method is characterized by the use of environmentally benign and sustainable iron salts for cross-coupling in the catalytic system, employing benign urea ligands in the place of reprotoxic NMP (NMP = N-methyl-2-pyrrolidone). It is notable that high selectivity for the cross-coupling is achieved in the presence of hydrolytically-labile and prone to nucleophilic addition phenolic ester C(acyl)–O bonds. The reaction provides access to alkyl-functionalized aryl benzoates. The examination of various O-coordinating ligands demonstrates the high activity of urea ligands in promoting the cross-coupling versus nucleophilic addition to the ester C(acyl)–O bond. The method showcases the functional group tolerance of iron-catalyzed Kumada cross-couplings.

An iron-catalysed allylation of organomagnesium reagents (alkyl, aryl) with simple allyl acetates proceeds under mild conditions (Fe(OAc)₂ or Fe(acac)₂, Et₂O, r.t.) to furnish various alkene and styrene derivatives.

Quinolyl triflates and isoquinolyl triflates undergo palladium-catalysed couplings with organostannanes, organoaluminiums and activated alkenes. The range of organic groups which can be transferred to the heteroaromatic substrate includes aryl, vinyl, alkynyl, alkyl and hydride.

HTE was used to systematically investigate the reaction of alkyl trifluoroborates and aryl bromides under photocatalytic conditions. General conditions were identified for coupling of activated primary, benzylic and secondary alkyl trifluoroborates.

We report the synthesis and characterization of meso-anthracenylporphyrins with zinc and nickel metal centers. A variety of novel aryl and alkyl meso-substituted anthracenylporphyrins were synthesized via step-wise Suzuki cross-coupling reactions using anthracenyl boronates. This method was compared to standard syntheses based on condensation reactions to yield anthracenylporphyrins of the A2B2- and A3B-type. The work was complemented by the synthesis of a number of the functionalized anthracene derivatives via Suzuki couplings. Selected systems were subjected to single-crystal X-ray analysis which revealed an unusual close packing for nickel(II) anthracenylporphyrins.

A protocol for the cross-coupling of azetidines with aryl, heteroaryl, vinyl and alkyl Grignard reagents has been developed under iron catalysis. In addition, a short formal synthesis of a pharmacologically active molecule was demonstrated.

Four new α-β-unsaturated alkyl-ester chiral amines were synthesized in excellent yields (77–95%) via peptide couplings from their corresponding α-β-unsaturated alkyl-ester anilines and N-Boc protected chiral aminoacids. To our delight, these polyfunctionalized compounds are being used as starting reagents in Ugi-type three-component reactions (Ugi-3CR) together with alkyl- and aryl-aldehydes and a chain-ring tautomerizable amino acid-containing isocyanide to synthesize novel oxazole-based macrocycle precursors. Thus, the aim of this communication is to show our most recent results of the synthesis and use of new and complex chiral amines to assemble macrocyclic polypeptides with potential application in medicinal chemistry, such as the post-surgical antibiotic Vancomycin.

Diisopropyl 8-bromo-2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine was used as a starting material for the synthesis of the 8-C-substituted 2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (PMEDAP) analogues. A systematic screening of diverse cross-coupling reactions was carried out. Stille, Suzuki–Miyaura, Negishi, and Sonogashira cross-couplings, as well as Pd-catalysed reactions with trialkylaluminiums, were employed for the introduction of various alkyl, alkenyl, alkynyl, aryl, and hetaryl substituents to the C-8 position of the 2,6-diaminopurine moiety. In contrast to the potent parent compound PMEDAP, which exhibits potent antiretroviral and antitumor activity, none of the sixteen newly synthesized 8-C-substituted analogues of PMEDAP showed any specific antiviral activity.

Ce travail de thèse vise à réaliser la formation de liaisons C(sp³)-C(sp²) et C(sp³)-C(sp³) par couplages croisés de Suzuki-Miyaura (S-M) et de Kumada à l'aide de catalyseurs de fer, nouvellement développés, et en mettant l'accent sur l'étude du potentiel applicative de ces catalyseurs en synthèse. Ce travail se concentre aussi sur la mise au point d'une méthode efficace et sélective de 1,2-dicarbofonctionnalisation d'alcènes promue par ces catalyseurs. Le chapitre 1 présente les premières découvertes des couplages croisés médiés par le fer et le développement de catalyseurs de fer pour les couplages croisés de S-M et de Kumada. Les formations de liaisons C(sp²)-C(sp²), C(sp²)-C(sp³) et C(sp³)-C(sp³) seront couvertes. La conception de ligands adaptés et les études mécanistiques ont joués un rôle crucial dans le développement du domaine. La section suivante présente l'état de l'art de la méthode de 1,2-dicarbofonctionnalisation des oléfines catalysées par les métaux abondants, en soulignant les stratégies développées pour surmonter les réactions secondaires indésirables. Le chapitre 2 traite de la réaction de S-M, dont l'utilisation s'est largement répandue en raison de sa large applicabilité, ainsi que de la stabilité, de la disponibilité et de la faible toxicité des réactifs organoborés. Tant en recherche académique qu'en l'industrie, la plupart des couplages de S-M sont dominés par des catalyseurs à base de palladium et de nickel. Récemment, le fer a fait l'objet d'une attention particulière en raison de sa forte abondance et de sa nature respectueuse de l'environnement. Malgré le rôle crucial du fer dans l'offre d'une catalyse plus durable pour le couplage de S-M, ce dernier impliquant des partenaires hybridés sp³ reste rare et se heurte à d'importantes limitations en termes de champ d'applications. Ce chapitre présente le développement d'un catalyseur de fer(II), versatile et de structure bien définie, qui réalise avec succès les couplages alkyle-aryle et alkyle-alkyle de S-M entre des halogénures d'alkyle et des esters boroniques (hétéro)arylés ou des dérivés boranes alkylés. Ces couplages ont été réalisés dans des conditions douces et ont montré une large compatibilité avec diverses fonctionnalités, y compris des N-, O- et S-hétérocycles importants en chimie médicinale. Les halogénures d'alkyle primaires, secondaires (Br, Cl, I) et tertiaires, ainsi que les esters boroniques neutres, riches et pauvres en électrons, de même que les boranes d'alkyle 1° et 2° sont compatibles et ont donné des rendements élevés à excellents. Des solvants plus écologiques ont été utilisés lors de la synthèse d'intermédiaires pharmaceutiques clés et d'un candidat médicament avec des rendements élevés, ce qui démontre un fort potentiel applicatif pour une production industrielle à grande échelle. Le chapitre 3 présente l'application du couplage croisé de S-M dans une méthode de 1,2-alkylarylation d'oléfines à trois composants, promue par un catalyseur de fer(II). Cette méthode facilite la formation de deux liaisons carbone-carbone en une seule étape de synthèse et représente le premier exemple de couplage de S-M combiné à une fonctionnalisation d'alcènes, conduisant sélectivement au produit de fonctionnalisation-1,2 alkyle-aryle. Bien que la méthodologie actuelle soit limitée par la nécessité d'un excès d'oléfines (10 équiv.) et d'esters boroniques donneurs en électrons, l'utilisation de réactifs borés démontre un potentiel pour des applications synthétiques plus larges. Le chapitre 4 étend l'application du catalyseur de fer(II) développé dans les chapitres 2 et 3, en démontrant son efficacité remarquable dans la réaction de couplage croisé de Kumada entre des halogénures d'alkyle hybridés sp³ et des réactifs organomagnésiens hybridés sp² et même sp³ dans des conditions douces. Cela souligne la grande polyvalence de ce catalyseur qui facilite le couplage de divers centres carbonés hybridés sp² et sp³, sans le besoin de conditions drastiques
This PhD research aims to achieve challenging C(sp³)-C(sp²) and C(sp³)-C(sp³) bond formations through Suzuki-Miyaura and Kumada cross-couplings using newly-designed iron-based catalysts, with an emphasis on their potential for synthetic applications. This work also focuses on achieving efficient and selective 1,2-dicarbofunctionalization of unactivated alkenes promoted by these catalysts. Chapter 1 primarily introduces the early discoveries of iron-mediated cross-couplings and the development of iron-based catalysts in Suzuki-Miyaura and Kumada cross-couplings, covering C(sp²)-C(sp²), C(sp²)-C(sp³), and C(sp³)-C(sp³) bond formations. The design of bespoke ligand and mechanistic investigations have played a crucial role in the development of this field. The following section introduces the state-of-the-art in earth-abundant metal-catalyzed 1,2-dicarbofunctionalization of olefins, highlighting strategies developed to overcome undesired side reactions. Chapter 2 covers the Suzuki-Miyaura reaction, which has gained widespread use due to its broad applicability, along with the stability, availability, and low toxicity of organoboron reagents. Most Suzuki-Miyaura couplings (SMC), both in academia and industry, are dominated by palladium and nickel catalysts. Recently, iron has garnered significant attentions due to its earth abundance and environmentally friendly nature. Despite the crucial role of iron in offering more sustainable catalysis for Suzuki-Miyaura coupling, iron-catalyzed SMC involving sp³-hybridized systems remains rare and faces significant scope limitations. This chapter reports on the development of a versatile, well-defined iron(II) catalyst that successfully facilitated C(sp3)-C(sp2) and C(sp3)-C(sp3) SMC of alkyl halide electrophiles with (hetero)aryl boronic esters and alkyl borane nucleophiles, respectively. These couplings were carried out under mild reaction conditions, exhibited broad functional group compatibility - including various medicinally important N-, O-, and S-based heterocycles. Primary, secondary alkyl halides (Br, Cl, I), and tertiary alkyl chlorides, as well as electron-neutral, electron-rich, and electron-poor boronic esters, alongside 1° and 2° alkyl boranes all were tolerated with high to excellent yields. Greener solvents were used in the synthesis of key intermediates relevant to pharmaceuticals and potential drug candidates with high yields, demonstrating significant potential for large-scale industrial production. Chapter 3 introduces the application of Suzuki-Miyaura cross-coupling in the three-component 1,2-alkylarylation of unactivated olefins, using a well-defined iron(II) catalyst. This method facilitates the formation of two carbon-carbon bonds in a single synthetic step and represents the first example of combining Suzuki-Miyaura cross-coupling and 1,2-functionalization of unactivated alkenes, selectively yielding the desired 1,2-alkylarylation product. Although the current methodology is limited by the requirement for an excess of olefins (10 equiv.) and electron-donating boronic esters, the use of boron reagents demonstrates a potential for broader synthetic applications. Chapter 4 extends the application of the iron(II) catalyst developed in Chapters 2 and 3, demonstrating its remarkable efficacy in catalyzing the Kumada cross-coupling reaction between C(sp³)-hybridized alkyl halides and either C(sp²)- or even C(sp³)-hybridized organomagnesium reagents under mild conditions. This achievement underscores the broad versatility of this catalyst in facilitating the coupling of diverse carbon centers, including both sp² and sp³ hybridizations, without requiring harsh conditions

Abstract Thirty three aryl and aryl alkyl phosphane ligands were prepared and characterized for catalytic purposes. The aryl groups in both types of ligands were modified with alkyl substituents (methyl, ethyl, isopropyl, cyclohexyl, phenyl) or hetero substituents (methoxy, N,N-dimethylaniline, thiomethyl). The alkyl groups directly attached to the phosphorous atom were ethyl, isopropyl or cyclohexyl. Mono- and in some cases also dinuclear palladium (II) complexes of the ligands were prepared and characterized. The syntheses of the palladium complexes are solvent-dependent and afford either mono- or dinuclear complexes depending on the choice of the solvent. Additionally, two 2-mercaptobenzothiazole palladium complexes were synthesized and characterized. A rare distorted lantern-type structure was presented for the first time. The ligands were characterized by 1H, 13C, 31P NMR spectroscopy and mass spectrometry. The palladium complexes were characterized by 31P NMR spectroscopy, X-ray crystallography and elemental analysis. Links between the NMR data of the palladium complexes and ligands and their catalytic activity was screened and correlation found. The crystal structures of the palladium complexes were studied for possible attractive interactions between two ligands. Such interactions were found from two examples. There is an attractive interaction between the phenyl and quinolinyl moieties of 2-quinolinyldiphenyl phosphane. A similar interaction was found between the methyl substitute and phenyl ring of o-tolylphosphane. The ligands and palladium complexes presented in this thesis were prepared in hope of finding suitable catalysts for Suzuki coupling reactions of various bulky aryl halides and phenyl boronic acids to prepare sterically hindered bi- and triaryls under microwave irradiation. A selection of aryl alkyl phosphane ligands catalyzed the couplings of bulky aryl bromides and even unactivated aryl chlorides efficiently and produced high yields. The reaction conditions of a new catalyst system were optimized, and it was noticed that the addition of a small amount of water enhanced the purity and yield of the coupling products further.

碩士
國立暨南國際大學
應用化學系
99
In this thesis, we are interested in converting endo formyl [2.2.1]bicyclic carbinols into a bicyclic [3.2.1]α-amino ketone. The consecutive condensation and ring expansion reactions of carbinols 47 and 71 are the most important steps. Compound 47 and compound 71 reacted with various kinds of primary amine which are N-nucleophiles, via intramolecular rearrangement to give ring expansion reaction products. The reaction had proved to be highly chemoselective、regioselective and stereoselective. The bicyclic [3.2.1]α-amino ketone is the final product. The alkyl or aryl group of primary amines might be methyl、ethyl、other alkyl, para-substituted electron donating or electron withdrawing aryl group. The mechanisms for the reactions of carbinols 47 and 71 with various primary amine are also discussed.

碩士
國立中興大學
化學系所
99
Abstract The acetylenic compounds are important building block in the fields of pharmaceutical chemistry and organic synthesis. The transition metal catalyzed coupling reaction of terminal alkynes with aryl halides has become one of the most important methods for preparing functionalized alkynes. Palladium and copper co-catalyzed system is well known as Sonogashira reaction, however, palladium is not only expensive but also highly toxic. Thus, develop the system by using copper as the sole metal source has gain much attention in recent years. The first part of this thesis, we report a highly efficient catalytic system employs the combination of Cu2O (1 mol %) with bisphosphine ligand, giving the products in good to excellent yields. Recently, aryl vinyl sulfides have been reported as drug candidates against drugresistant strains of tuberculosis and anthrax, in addition to many other drug-resistant Gram-positive bacteria. Addition of thiols to alkynes through a radical pathway is a common way to prepare these compounds, however, this method will produce the undesired regioisomers at the same time. Transition metals including palladium, cobalt and copper have been reported for coupling reaction of thiols with vinyl halides. The second part of this thesis, we report the first iron-catalyzed coupling reaction of thiols with vinyl halides in the presence of a bisphosphine ligand, giving the aryl vinyl sulfide in good yields.

Boronic acid(esters) have been well recognized as an indispensable coupling partner in the Suzuki-Miyaura cross coupling reactions producing a vast spectrum of molecules, applicable in the diverse field ranging from medicinal to materials sciences.[1] Transition metal catalyzed synthesis of boronic esters from diborons with the assistance of bases is a well-established methodology[2]. In this thesis, the cobalt-N-Heterocyclic carbene complexes catalyzed borylation of organic compounds and interaction of diazabutadienes with diboron compounds will be discussed. (i) In the first section, Co(IMes)2Cl2 catalyzed borylation of aryl halides will be discussed. [3a] The robust protocol, operating under mild condition facilitate the borylation of a diverse range of aryl halides with great efficacy, which includes the challenging aryl chlorides. The preliminary mechanistic studies suggest that base-bis(pinacolato)diboron adduct reduces the Co(IMes)2Cl2 complex to generate Co(IMes)2Cl complex, which acts as an active catalytic species. (ii) The second section deals with catalytic synthesis of primary and secondary alkyl boronic esters using alkyl halides. [3b] The in situ generated Co-NHC complex, in assistance with base and diboron compound, produces the corresponding borylated product from alky halides. The reaction proceeds under very mild conditions and covers a wide range of alkyl halides, including chlorides having different functional groups. (iii) In the third section, development in selective hydroboration of vinyl arenes and aliphatic alkenes will be discussed. [3c] Catalyzed by Co(I)NHC complex, the alkene hydroboration by pinacol borane gives Markovnikov selective product with good selectivity, where the regio-selectivity is controlled by phenyl substituent. In absence of that, complete inversion in the selectivity has been observed. The preliminary mechanistic cycle suggests that the catalytic cycle proceeds via oxidative addition of pinacol borane to [Co] followed by alkene insertion and reduction elimination steps. (iv) The last section discusses the interaction of diazabutadiene molecules with diboron compounds. [3d] The diazabutadiene derivatives have been observed to completely cleave the B-B bond of Bis(catacolato)diboron and Bis(dithiocatacolato)diboron. The preliminary findings hint towards homolytic cleavage of the B-B bond by concerted interaction of the two nitrogen atoms of diazabutadiene with the two boron atoms of the diboron from the same face. References: [1] Boronic Acids-Preparation and Applications in Organic Synthesis, Medicine and Materials, 2nd ed.; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2011. [2] Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse. Chem. Rev. 2016, 116, 9091-9161. [3] (a) Verma, P. K.; Mandal, S.; Geetharani, K. ACS Catal. 2018, 8, 4049-4054. (b) Verma, P. K.; Prasad, K. S.; Varghese, D.; Geetharani, K. Org. Lett. 2020, 22, 4, 1431-1436. (c) Verma, P. K.; Setulekshmi, A. S.; Geetharani, K. Org. Lett. 2018, 20, 7840-7845. (d) Verma, P. K.; Meher, N. K.; Geetharani, K. Accepted for publication in Chem. Commun., Manuscript ID: CC-COM-06-2021-002881.R2.

AbstractRadicals can be generated by the cleavage of the C—B bond of alkylboranes or boronic acid derivatives. The fragmentation process may result from a nucleohomolytic substitution process or from a redox process. The nucleohomolytic substitution is ideal for the generation of alkyl radicals and is usually part of a chain-reaction process. Redox processes (mainly oxidative reactions) have been used to generate both alkyl and aryl radicals. The use of stoichiometric oxidizing agents can be avoided by employing photoredox catalysis. A broad range of synthetic applications such as radical cascade processes, multicomponent reactions, and cross-coupling reactions in the presence of suitable metal catalysts are now possible. In their diversity, organoboron compounds represent one of the most general sources of radicals. The merging of radical chemistry with the classical chemistry of organoboron derivatives opens tremendous opportunities for applications in organic synthesis.

Yuqing Hou of Southern Illinois University found (J. Org. Chem. 2009, 74, 6362) that the peroxy ether 2 served effectively to directly transfer a methoxy group to the lithiated 1 to give 3. Wanzhi Chen of Zhejiang University, Xixi Campus, showed (J. Org. Chem. 2009, 74, 7203) that pyrimidines such as 4, readily prepared from the corresponding phenol, underwent smooth Pd-catalyzed ortho acetoxylation. Trond Vidar Hansen of the University of Oslo observed (Tetrahedron Lett. 2009, 50, 6339) that simple electrophilic formylation of phenols such as 6 also proceeded with high ortho selectivity. Kyung Woon Jung of the University of Southern California optimized (J. Org. Chem. 2009, 74, 6231) the Rh catalyst for ortho C-H insertion, converting 8 into 9. Jin-Quan Yu of Scripps/La Jolla devised (Science 2010, 327, 315) a protocol for carboxy-directed catalytic ortho palladation that allowed subsequent Heck coupling, transforming 10 into 11. Norikazu Miyoshi of the University of Tokushima established (Chem. Lett. 2009, 38, 996) that in situ generated strontium alkyls added 1,6 to benzoic acid 13, to give, after mild oxidative workup, the 4-alkyl benzoic acid 15. Amin Zarei of Islamic Azad University showed (Tetrahedron Lett. 2009, 50, 4443) that their previously developed protocol for preparing stable diazonium silica sulfates could be extended to the preparation of an aryl azide such as 17. Stephen L. Buchwald of MIT developed (J. Am. Chem. Soc. 2009, 131, 12898) a Pd-mediated protocol for the conversion of aryl chlorides to the corresponding nitro aromatics. Virgil Percec of the University of Pennsylvania has also reported (Organic Lett. 2009, 11, 4974) the conversion of an aryl chloride to the borane, and Guy C. Lloyd-Jones has described (Angew. Chem. Int. Ed. 2009, 48, 7612) the conversion of phenols to the corresponding thiols. Kwang Ho Song of Korea University and Sunwoo Lee of Chonnam National University demonstrated (J. Org. Chem. 2009, 74, 6358) that the Ni-mediated homologation of aryl halides worked with a variety of primary and secondary formamides. Kwangyong Park of Chung-Ang University observed (J. Org. Chem. 2009, 74, 9566) that Ni catalysts also mediated the coupling of Grignard reagents with the tosylate 22 not in the usual way but with the C-S bond to give 23.

Jianbo Wang of Peking University described (Angew. Chem. Int. Ed. 2010, 49, 2028) the Au-promoted bromination of a benzene derivative such as 1 with N-bromosuccinimide. In a one-pot procedure, addition of a Cu catalyst followed by microwave heating delivered the aminated product 2. Jian-Ping Zou of Suzhou University and Wei Zhang of the University of Massachusetts, Boston, observed (Tetrahedron Lett. 2010, 51, 2639) that the phosphonylation of an arene 3 proceeded with substantial ortho selectivity. Yonghong Gu of the University of Science and Technology, Hefei, showed (Tetrahedron Lett. 2010, 51, 192) that an arylpropanoic acid 6 could be ortho hydroxylated with PIFA to give 7. Louis Fensterbank, Max Malacria, and Emmanuel Lacôte of UMPC Paris found (Angew. Chem. Int. Ed. 2010, 49, 2178) that a benzoic acid could be ortho aminated by way of the cyano amide 8. Daniel J. Weix of the University of Rochester developed (J. Am. Chem. Soc. 2010, 132, 920) a protocol for coupling an aryl iodide 10 with an alkyl iodide 11 to give 12. Professor Wang devised (Angew. Chem. Int. Ed. 2010, 49, 1139) a mechanistically intriguing alkyl carbonylation of an iodobenzene 10. This is presumably proceeding by way of the intermediate diazo alkane. Usually, benzonitriles are prepared by cyanation of the halo aromatic. Hideo Togo of Chiba University established (Synlett 2010, 1067) a protocol for the direct electrophilic cyanation of an electron-rich aromatic 15. Thomas E. Cole of San Diego State University observed (Tetrahedron Lett. 2010, 51, 3033) that an alkyl dimethyl borane, readily prepared by hydroboration of the alkene with BCl3 and Et3 SiH, reacted with benzoquinone 17 to give 18. Presumably this transformation could also be applied to substituted benzoquinones. When a highly substituted benzene derivative is needed, it is sometimes more economical to construct the aromatic ring. Joseph P. A. Harrity of the University of Sheffield and Gerhard Hilt of Philipps-Universität Marburg showed (J. Org. Chem. 2010, 75, 3893) that the Co-catalyzed Diels-Alder cyloaddition of alkynyl borinate 21 with a diene 20 proceeded with high regiocontrol, to give, after oxidation, the aryl borinate 22.

Several remarkable one-carbon homologations have recently appeared. André B. Charette of the Université de Montréal reported (J. Org. Chem. 2008, 73, 8097) the alkylation of diiodomethane with alkyl iodides such as 1, to give the diiodoalkane 2. Carlo Punta and the late Ombretta Porta of the Politecnico di Milano effected (Organic Lett. 2008, 10, 5063) reductive condensation of an amine 3 with an aldehyde 4 in the presence of methanol, to give the amino alcohol 5. Timothy S. Snowden of the University of Alabama showed (Organic Lett. 2008, 10, 3853) that NaBH4 reduced the carbinol 7, easily prepared from the aldehyde 6, to the acid 8. Ram N. Ram of the Indian Institute of Technology, Delhi found (J. Org. Chem. 2008, 73, 5633) that CuCl reduced 7 to the chloro ketone 9. Kálmán J. Szabó of Stockholm University extended (Chem. Commun. 2008, 3420) his elegant work on in situ borinate formation, coupling, in one pot, the allylic alcohol 10 with the acetal 11 (hydrolysed in situ) to deliver the alcohol 12 as a single diastereomer. Samir Z. Zard of the Ecole Polytechnique developed (J. Am. Chem. Soc. 2008, 130, 8898) the 6-fluoropyridyloxy ether of 13 as an effective radical leaving group, enabling efficient coupling with 14, activated by dilauroyl peroxide, to give 15. Shu Kobayashi of the University of Tokyo established (Chem. Commun. 2008, 6354) that the anion of the sulfonyl imidate 17 participated in direct Pd-mediated allylic coupling with the carbonate 16. The product sulfonyl imidate 18 is itself of medicinal interest. It is also easily converted to other functional groups, including the aldehyde 19. Jianliang Xiao of the University of Liverpool found (J. Am. Chem. Soc. 2008, 130, 10510) that Pd-mediated coupling of an aldehyde 21 in the presence of pyrrolidine led to the ketone 22. The reaction is probably proceeding via Heck coupling of the aryl halide with the in situ generated enamine. Alois Fürstner of the Max Planck Institut, Mülheim observed (J. Am. Chem. Soc. 2008, 130, 8773) that in the presence of the simple catalyst Fe(acac)3 a Grignard reagent 24 coupled smoothly with an aryl halide 23 to give 25.

Several new methods for the direct functionalization of Ar-H have appeared. Hisao Yoshida of Nagoya University observed (Chem. Comm. 2008, 4634) that under irradiation, TiO2 in water effected meta hydroxylation of benzonitrile 1 to give the phenol 2. Anisole showed ortho selectivity, while halo and alkyl aromatics gave mixtures. Melanie S. Sanford of the University of Michigan reported (J. Am. Chem. Soc. 2008, 130, 13285) a complementary study of Pd-catalyzed ortho acetoxylation. Jin-Quan Yu of Scripps/La Jolla developed (Angew. Chem. Int. Ed. 2008, 47, 5215) a Pd-catalyzed protocol for ortho halogenation of aromatic carboxylates such as 3. A related protocol (J. Am. Chem. Soc. 2008, 130, 17676) led to ortho arylation. Trond Vidar Hansen of the University of Oslo devised (Tetrahedron Lett. 2008, 49, 4443) a one-pot procedure for the net ortho cyanation of phenols such as 5 to the salicylnitrile 6. Robin B. Bedford of the University of Bristol, Andrew J. M. Caffyn of the University of the West Indies and Sanjiv Prashar of the Universidad Rey Juan Carlos established (Chem. Comm. 2008, 990) a Rh-catalyzed protocol for ortho arylation of phenols such as 7. Laurent Désaubry of the Université Louis Pasteur observed (Tetrahedron Lett. 2008, 49, 4588) regioselective coupling of unsymmetrical difluorobenzenes such as 9 to give the ether 10. Fuk Yee Kwong of Hong Kong Polytechnic University extended (Angew. Chem. Int. Ed. 2008, 47, 6402) Pd-mediated amination to the notoriously difficult mesylates, such as 11. John F. Hartwig of the University of Illinois reported (J. Am. Chem. Soc. 2008, 130, 13848) a related method for the amination of aryl tosylates. Hong Liu of the Shanghai Institute of Materia Medica found (Organic Lett. 2008, 10, 4513) that the Fe-catalyzed amination of aryl halides such as 13 sometimes gave mixtures of regioisomers. Hideki Yorimitsu and Koichiro Oshima of Kyoto University effected (Angew. Chem. Int. Ed. 2008, 47, 5833) Ag-catalyzed Grignard cross coupling with aryl halides, converting 15 into 16. Note that silyl aromatics such as 16 are readily reduced under dissolving metal conditions to give allyl silanes.

Primary amines are combined with an aldehyde group to generate Schiff base compounds, which are called condensation imine products. This class of compounds has a general structure, R-C=NR\', where R and R\' represent alkyl/aryl/cyclohexyl/heterocyclic group. These compounds contain an azomethine group that is basic in nature due to, (i) the presence of lone pair of electrons on the nitrogen and (ii) electron-donating nature of the double bond. Hence, these compounds, as ligands, participate in the formation of metal complexes. The presence of lone pair of electrons on the nitrogen atom and the hybridization involved explains the physical, chemical, and spectral properties of nitrogen-containing moieties. In the case of (sp2) hybridization (trigonal structure), the lone pair of electrons occupies either a symmetrical unhybridized 2p orbital that is perpendicular to the plane of trigonal hybrids or a symmetrical hybrid orbital, whose axis is in the plane, leaving behind only the π-electrons in the unhybridized 2p orbital. A very similar type of hybridization is experienced by the nitrogen atom in the azomethine group. Traditional phosphine complexes of nickel, palladium, and platinum, particularly those of palladium, have played an extremely important role in the development of homogeneous catalysis. Schiff base complexes as catalysts have been studied for various organic transformations such as oxidation, epoxidation, reduction, coupling reactions, polymerization reactions, hydroformylations, and many more.

Tohru Fukuyama of the University of Tokyo and Toshiyuki Kan of the University of Shizuoka devised ( J. Am. Chem. Soc. 2008, 130, 16854) the chiral auxiliary-directed Rh-mediated cyclization of 1, setting the two stereogenic centers of 2 with high stereocontrol. The ester 2 was carried on to the indole alkaloid (-)-Serotobenine 3. In the course of a synthesis of (-)-Aureonitol 6, Liam R. Cox of the University of Birmingham developed (J. Org. Chem. 2008, 73, 7616) the diastereoselective intramolecular addition of an allyl silane 4 to give the tetrahydrofuran 5. In analogy to what is known about the intramolecular ene reaction, the diastereocontrol observed for this cyclization may depend on the allyl silane being Z. Michel R. Gagné of the University of North Carolina found (J. Am. Chem. Soc. 2008, 130, 12177) that the Ni-catalyzed coupling of organozinc halides could be extended to glycosyl halides such as 7. This opened ready access to C -alkyl and C -aryl glycosides, including Salmochelin SX 10. Isamu Shiina of the Tokyo University of Science established (Organic Lett. 2008, 10, 3153) that the acid-mediated cyclization of the Sharpless-derived epoxide 10 proceeded with clean inversion, to give 11. The highly-substituted tetrahydropyran core 11 was then elaborated to the antifungal Botcinin F 12. Ian Paterson of Cambridge University optimized (Organic Lett. 2008, 10, 3295) the Pd-catalyzed spirocyclization of the ene diol 13, leading to 14, the enantiomerically-pure bicyclic core of (-)-Saliniketal B 15. Haterumalide NA 18 presented the particular challenge of assembling the geometrically-defined chloroalkene, in addition to closing the macrolide ring. Babak Borhan of Michigan State University addressed (J. Am. Chem. Soc. 2008, 130, 12228) both of these challenges together, electing to employ a chlorovinylidene chromium carbenoid, as developed by Falck and Mioskowski, to effect the macrocyclization of 16 to 17.

Alcohols are usually protected as alkyl or silyl ethers. Michael P. Jennings of the University of Alabama found (Tetrahedron Lett. 2008, 49, 5175) that pyridinium tribromide can selectively remove the TBS (or TES) protection from the primary alcohol of a protected primary-secondary alcohol such as 1. Propargyl ethers are useful because they are stable, but can be selectively removed in the presence of other protecting groups. Shino Manabe and Yukishige Ito at RIKEN showed (Tetrahedron Lett. 2008, 49, 5159) that SmI2 could reductively remove a propargyl group in the presence of acetonides (illustrated, 3), MOM, benzyl and TBS ethers. Hisanaka Ito of the Tokyo University of Pharmacy and Life Sciences took advantage (Organic Lett. 2008, 10, 3873) of the reducing power of Cp2Zr to selectively remove the allyl ethers from 5, to give 6. These conditions might also remove propargyl ethers. Esters can also be useful protecting groups. Naoki Asao of Tohoku University developed (Tetrahedron Lett . 2008, 49, 7046) the o-alkynyl ester 7. Au catalyst in EtOH removed the ester, leaving benzoates, acetates, OTBS and OTHP intact. Alternatively, an o-iodobenzoate can be removed by Sonogashira coupling followed by the Au hydrolysis. N-Formylation is usually accomplished using mixed anhydrides. Weige Zhang and Maosheng Chang of Shenyang Pharmaceutical University put forward ( Chem. Commun. 2008 , 5429) an intriguing alternative, heating a secondary amine 9 with KCN in the presence of dimethyl malonate to give 10. Many of the current methods for amination that have been developed deliver the aryl amine. John F. Hartwig of the University of Illinois established (J. Am. Chem. Soc. 2008, 130, 12220) that exposure of the amine 11 to Boc2O followed by CAN led to the protected, dearylated amine 12. Adam McCluskey of The University of Newcastle observed (Tetrahedron Lett. 2008, 49, 6962) that microwave heating removed Boc protecting groups when there was a free carboxylic acid elsewhere in the molecule. Michael Lefenfeld of SiGNa Chemistry and James E. Jackson of Michigan State University used (Organic Lett. 2008, 10, 5441) easilyhandled Na/silica gel to remove primary and secondary sulfonamides (e.g. 15 → 16). Methanesulfonamides were also removed under these conditions.

Jin K. Cha of Wayne State University described (J. Org. Chem. 2009, 74, 5528) the diastereoselective intramolecular cyclopropanation of nitriles with homoallylic alcohols such as 1 . Valery V. Fokin of Scripps/La Jolla found (J. Am. Chem. Soc. 2009, 131, 18034) that the diazoimine derived from 4 could add with high enantioselectivity to aryl alkenes, including styrene 5. Andreas Gansäuer of the University of Bonn optimized (Angew. Chem. Int. Ed. 2009, 48 , 8882; Tetrahedron 2009, 65, 10791) the Ti catalyst to enable efficient cyclization of substrates such as 7 to the corresponding cyclobutanes. F. Dean Toste of the University of California, Berkeley, devised (J. Am. Chem. Soc. 2009, 131, 9178) a gold catalyst for the enantioselective ring expansion of a prochiral allene such as 9 to the cyclobutanone 10. David J. Procter of the University of Manchester developed (J. Am. Chem. Soc. 2009, 131, 15467) the SmI2 -mediated cyclization of a lactone such as 11 to the cyclopentanone 12. Shigeki Matsunaga and Masakatsu Shibasaki of the University of Tokyo designed (Chem. Commun. 2009, 5138) a Ni catalyst for the enantioselective condensation of 13 with formaldehyde. Some acyclic β-keto esters could also be hydroxymethylated with high enantiocontrol. Darren J. Dixon, also of the University of Manchester, devised (J. Am. Chem. Soc. 2009, 131, 9140) a Cu catalyst for the enantioselective Conia cyclization of 15 to 16 . K. C. Nicolaou, also of Scripps/La Jolla, reported (Angew. Chem. Int. Ed. 2009, 48, 6293) a Rh catalyst for the related cyclization of 17 to 18. Ryo Shintani and Tamio Hayashi of Kyoto University showed (J. Am. Chem. Soc. 2009, 131, 13588) that a Rh catalyst could effect enantioselective conjugate addition of a tetraaryl borate even to a 3-methyl cyclohexenone 19, to establish the cyclic quaternary center. Alexandre Alexakis of the University of Geneva established (Chem. Commun . 2009, 3868) that with the easily ionized allylic bromide 21, Cu-mediated coupling with the alkyl Grignard 22 proceeded with substantial asymmetric induction. Jon D. Rainier of the University of Utah devised (Organic Lett. 2009, 11, 38774) conditions for effecting Ti-mediated intramolecular metathesis between an alkene and a lactam carbonyl, giving the cyclic enamide 24.