Total synthesis

About: Total synthesis is a research topic. Over the lifetime, 25578 publications have been published within this topic receiving 489319 citations.

Organic Synthesis Highlights

Abstract: Preface.List of Contributors.PART I. SYNTHETIC METHODS.Direct Conversion of Sugar Glycosides into Carbocycles (Peter I. Dalko and Pierre Sinay).Synthesis of Diaryl Ethers: A Long-Standing Problem Has Been Solved (Fritz Theil).Take The Right Catalyst: Palladium-Catalyzed CC-, CN- and CO-Bond Formation on Chloro-Arenes (Rainer Stumer).Alkyne Metathesis in Natural Product Synthesis (Thomas Lindel).Transition Metal-Catalyzed Functionalization of Alkanes (Oliver Seitz).An Eldorado for Homogeneous Catalysis? (Gerald Dyker).New and Selective Transition Metal Catalyzed Reactions of Allenes (A. Stephen K. Hashmi).Controlling Stereoselectivity with the Aid of a Reagent-Directing Group (Bernhard Breit).Solvent-Free Organic Syntheses (Jurgen O. Metzger).Fluorous Techniques: Progress in Reaction-Processing and Purification (Ulf Diederichsen).Recent Developments in Using Ionic Liquids as Solvents and Catalysts for Organic Synthesis (Peter Wasserscheid).Recent Advances on the Sharpless Asymmetric Aminohydroxylation (Dmitry Nilov and Oli ver Reiser).Asymmetric Phase Transfer Catalysis (Christabel Carter and Adam Nelson).Asymmetric Catalytic Aminoalkylations: New Powerful Methods for the Enantioselective Synthesis of Amino Acid Derivatives, Mannich Bases, and Homoallylic Amines (Michael Arend and Xiaojing Wang).IBX - New Reactions with an Old Reagent (Thomas Wirth).Parallel Kinetic Resolutions (Jason Eames).The Asymmetric Baylis-Hillman-Reaction (Peter Langer).Simple Amino Acids and Short-Chain Peptides as Efficient Metal-free Catalysts in Asymmetric Syntheses (Harald Groger, et al.).Recent Developments in Catalytic Asymmetric Strecker-Type Reactions (Larry Yet).Highly Enantioselective or Not? - Chiral Monodentate Monophosphorus Ligands in the Asymmetric Hydrogenation (Igor V. Komarov and Armin Borner).Improving Enantioselective Fluorination Reactions: Chiral N-Fluoro Ammonium Salts and Transition Metal Catalysts (Kilian Muniz).Catalytic Asymmetric Olefin Metathesis (Amir H. Hoveyda and Richard R. Schrock).Activating Protecting Groups for the Solid Phase Synthesis and Modification of Peptides, Oligonucleotides and Oligosaccharides (Oliver Seitz).Traceless Linkers for Solid-Phase Organic Synthesis (Florencio Zaragoza Dorwald).Merging Solid-Phase and Solution-Phase Synthesis: The "Resin-Capture- Release" Hybrid Technique (Andreas Kirschning and Rudiger Wittenberg).Polymeric Scavenger Reagents in Organic Synthesis (Jason Eames and Michael Watkinson).PART II. APPLICATIONS.Total Syntheses of Vancomycin (Lars H. Thoresen and Kevin Burgess).Bryostatin and Their Analogues (Ulf Diederichsen).Eleutherobin: Synthesis, Structure/Activity Relationship, and Pharmacophore (Ulf Diederichsen).Total Synthesis of the Natural Products CP-263,114 and CP-225,917 (Ulf Diederichsen and Katrin B. Lorenz).Polyene Cyclization to Adociasulfate 1 (Thomas Lindel and Cordula Hopmann).Sanglifehrin A: An Immunosuppressant Natural Product from Malawi (Thomas Lindel).Short Syntheses of the Spirotryprostatins (Thomas Lindel).The Chemical Total Synthesis of Proteins (Oliver Seitz).Solid-Phase Synthesis of Oligosaccharides (Ulf Diederichsen and Thomas Wagner).Polymer-Supported Synthesis of Non-Oligomeric Natural Products (Stefan Sommer, et al.).Explosions as a Synthetic Tool? Cycloalkynes as Precursors to Fullerenes, Buckytubes and Buckyonions (Rudiger Faust).Dendralenes: From a Neglected Class of Polyenes to Versatile Starting Materials in Organic Synthesis (Henning Hopf).Fascinating Natural and Artificial Cyclopropane Architectures (Rudiger Faust).Index.

Syntheses and Transformations of α-Amino Acids via Palladium-Catalyzed Auxiliary-Directed sp3 C–H Functionalization

Abstract: α-Amino acids (αAA) are one of the most useful chiral building blocks for synthesis. There are numerous general strategies that have commonly been used for αAA synthesis, many of which employ de novo synthesis focused on enantioselective bond construction around the Cα center and others that consider conversion of existing αAA precursors carrying suitable functional groups on side chains (e.g., serine and aspartic acid). Despite significant advances in synthetic methodology, the efficient synthesis of enantiopure αAAs carrying complex side chains, as seen in numerous peptide natural products, remains challenging. Complementary to these "conventional" strategies, a strategy based on the selective functionalization of side chain C-H bonds, particularly sp(3) hybridized C-H bonds, of various readily available αAA precursors may provide a more straightforward and broadly applicable means for the synthesis and transformation of αAAs. However, many hurdles related to the low reactivity of C(sp(3))-H bonds and the difficulty of controlling selectivity must be overcome to realize the potential of C-H functionalization chemistry in this synthetic application. Over the past few years, we have carried out a systematic investigation of palladium-catalyzed bidentate auxiliary-directed C-H functionalization reactions for αAA substrates. Our strategies utilize two different types of amide-linked auxiliary groups, attached at the N or C terminus of αAA substrates, to exert complementary regio- and stereocontrol on C-H functionalization reactions through palladacycle intermediates. A variety of αAA precursors can undergo multiple modes of C(sp(3))-H functionalization, including arylation, alkenylation, alkynylation, alkylation, alkoxylation, and intramolecular aminations, at the β, γ, and even δ positions to form new αAA products with diverse structures. In addition to transforming αAAs at previously unreachable positions, these palladium-catalyzed C-H functionalization strategies enable new retrosynthetic logic for the synthesis of many basic αAAs from a common alanine precursor. This approach reduces the synthetic difficulty for many αAAs by bypassing the requirement for stereocontrol at Cα and relies on straightforward and convergent single-bond coupling transformations at the β-methyl position of alanine to access a wide range of β-monosubstituted αAAs. Moreover, these β-monosubstituted αAAs can undergo further C-H functionalization at the β-methylene position to generate various β-branched αAAs in a stereoselective and programmable fashion. These new strategies offer readily applicable methods for synthesis of challenging αAAs and may facilitate the efficient total synthesis of complex peptide natural products.

A simple and modular strategy for small molecule synthesis: iterative Suzuki-Miyaura coupling of B-protected haloboronic acid building blocks.

Abstract: We herein describe a simple and highly modular strategy for small molecule synthesis involving the iterative cross-coupling of B-protected bifunctional haloboronic acids. Enabling this approach, we have newly discovered that the pyramidalization of boronic acids via complexation with the trivalent ligand N-methyliminodiacetic acid inhibits their reactivity towards cross-coupling. This ligand is remarkably stable to anhydrous Suzuki−Miyaura conditions yet readily cleaved using mild aqueous base (1 M aqueous NaOH/THF, 10 min, 23 °C or saturated aqueous NaHCO3/MeOH, 23 °C, 6 h). Although the reactivity of aryl, heteroaryl, alkenyl, and alkyl boronic acids can vary dramatically, this methodology is effective for protecting and deprotecting all four classes of nucleophiles. Harnessing this potential, we achieved the first total synthesis of the natural product ratanhine using the Suzuki−Miyaura reaction iteratively to bring together a collection of easily synthesized, readily purified, and highly robust buildi...