DOCSLIB.ORG

Stereoselective Synthesis: Chiral Auxiliaries

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Stereoselective Synthesis: Chiral Auxiliaries 1 Stereoselective synthesis: chiral auxiliaries Chiral auxiliaries couple to form new chiral compound substrate + substrate (achiral) chiral (achiral) chiral auxiliary auxiliary product overall diastereoselective chiral reaction reaction auxiliary resolve other diastereoisomer product cleave chiral product (chiral) auxiliary + chiral chiral auxiliary auxiliary • Chiral auxiliary - allows enantioselective synthesis via diastereoselective reaction • Add chiral unit to substrate to control stereoselective reaction • Can act as a built in resolving agent (if reaction not diastereoselective) • Problems - need point of attachment ....................adds additional steps ....................cleavage conditions must not damage product! 123.702 Organic Chemistry 2 Chiral auxiliary and addition to the carbonyl group • We have seen many examples of substrate control in nucleophilic addition to the carbonyl group (Felkin-Ahn & chelation control) • If molecule does not contain a stereogenic centre then we can use a chiral auxiliary • The chiral auxiliary can be removed at a later stage L Me L Me O MeMgBr Me Mg O O Me Ph –78°C Me Ph O Me O OH O O O Me H H Me H Me Me 98% de Me • Opposite diastereoisomer can be obtained from reduction of the ketone • Note: there is lower diastereoselectivity in the second addition as the nucleophile, ...‘H–’ is smaller Me Me O O KBH(i-OPr) Me Ph 3 Me Ph O OH O O Me Me Me Me H 90% de 123.702 Organic Chemistry 3 Chiral auxiliary in synthesis Me Me O Me RMgBr Me O Me Ph HO OH Me Ph –78°C OH LiAlH4 O O O Me Me Me Me Me O3 –78°C O Me O Me (–)-frontalin 100% ee • The chiral auxiliary, 8-phenylmenthol, has been utilised to form the pheromone, frontalin • Aggregation pheromone of the Southern Pine Beetle - the most destructive beetle to pine forests in southeastern united states 123.702 Organic Chemistry 4 Stereoselective synthesis: chiral reagents Chiral reagents chiral reagent substrate interacts with (achiral) achiral substrate reaction product substrate + (chiral) + (achiral) chiral dead reagent reagent chiral reagent chiral complex • Chiral reagent - stereochemistry initially resides on the reagent • Advantages - No coupling / cleavage steps required ........................Often override substrate control ........................Can be far milder than chiral auxiliaries • Disadvantages - Need a stoichiometric quantity (not atom economic) .............................Frequently expensive .............................Problematic work-ups 123.702 Organic Chemistry 5 Chiral reagents • Clearly, chiral reagents are preferable to chiral auxiliaries in that they function independent of the substrate’s chirality or on prochiral substrates • A large number have been developed for the reduction of carbonyls • Most involve the addition of a chiral element to one of our standard reagents Me H O Me H O B + B + Me L S Me R R Me Me (+)-α-pinene 9-BBN•THF alpine borane® proceeds via boat- like transition state can be reused Me H OH + B Me L S O R R Me H RL Me Me Me RS O H OH alpine borane® selectivity governed (CH ) Me (CH ) Me by 1,3-diaxial 2 4 2 4 interactions small group as linear 86% ee 123.702 Organic Chemistry 6 Binol derivative of LiAlH4 1. (S)-BINAL–H O H OMOM 2. MOM–Cl Me Me SnBu3 SnBu3 93% ee O OEt Al O H Li (R)-BINAL–H • Reducing reagent based on BINOL and lithium aluminium hydride • Selectivity is thought to arise from a 6-membered transition state (surprise!!) • Largest substituent (RL) adopts the pseudo-equatorial position and the small substituent (RS) is axial to minimise 1,3-diaxial interactions O RS Al Li O O H O Et RL 123.702 Organic Chemistry 7 Chiral reagent in total synthesis Cl Me H Ipc O B H OH BCl O Me H Ph Cl Cl Me Me Me Me 2 Cl (+)-Ipc2BCl ≥99% e.e. 1 recrystallisation ArOH, PPh3 EtO2C N N CO2Et CF3 CF3 i. MeNH2, H2O, 130°C ii. HCl O H O H Me N Cl H•HCl R-(–)-fluoxetine Prozac • (+)-Ipc2BCl is a more reactive, Lewis acidic version of Alpine-borane • Might want to revise the Mitsunobu reaction (step 2) • M. Srebnik, P.V. Ramachandran & H.C. Brown, J. Org. Chem., 1988, 53, 2916 123.702 Organic Chemistry 8 Chiral allyl boron reagents L L L L RZ B B H2O2 OH O O L O NaOH + E B R RZ R R R L R RZ RE RE RZ RE • Allyl boron reagents have been used extensively in the synthesis of homoallylic alcohols • Reaction always proceeds via coordination of Lewis basic carbonyl and Lewis acidic boron • This activates carbonyl as it is more electrophilic and weakens B–C bond, making the reagent more nucleophilic • Funnily enough, reaction proceeds by a 6-membered transition state H L H L H R H H OH B B L vs L RE RE RE O O OH R H R R RZ RE RZ RZ RZ E-alkene gives anti product Z-alkene gives syn product disfavoured • Aldehyde will place substituent in pseudo-equatorial position (1,3-diaxail strain) • Therefore alkene geometry controls the relative stereochemistry (like aldol rct) 123.702 Organic Chemistry 9 Chiral allyl boron reagents II Me OH B O + Et Me Me Et H Me Me 2 92% ee crotyl group orientated away from Me Me pinene methyl groups Me H H H OH B Me Et H O Me Me Et Me Me substituent pseudo- equatorial • Reagent is synthesized from pinene in two steps • Gives excellent selectivity but can be hard to handle (make prior to reaction) • Remember pinene controls absolute configuration Geometry of alkene controls relative stereochemistry 123.702 Organic Chemistry 10 Other boron reagents RZ Z Me Ts R E B R O E N B R B RE i-PrO2C Ph Me RZ O N Ts Me 2 i-PrO2C Ph attacks on si face of RCHO attacks on si face of RCHO attacks on re face of RCHO tartaric acid derivative • A number of alternative boron reagents have been developed for the synthesis of homoallylic alcohols • These either give improved enantiomeric excess, diastereoselectivity or ease of handling / practicality • Ultimately, chiral reagents are wasteful - they need at least one mole of reagent for each mole of substrate • End by looking at chiral catalysts 123.702 Organic Chemistry 11 Chiral reagent in total synthesis Ar OBn O OBn OH N Me DCM, 0°C BnO2C + Si BnO2C O H O N Cl 80% Me Me 95% d.e. Me Me Me Ar Cl H Ar H H Si N Me Me O N OH R R H H Ar H • Silicon reagent developed by J. Leighton • Used in the synthesis of (+)-SCH 351448, a reagent for the activation of low-density lipoprotein receptor (LDLR) promoter (no I don't know what it means either!) • Sergei Bolshakov & James L. Leighton, Org. Lett., 2005, 7, 3809 OH O O O OH Me CO2H Me Me O O Me Me NaO2C Me OH O O O HO (+)-SCH 351448 123.702 Organic Chemistry 12 Stereoselective synthesis: chiral catalysis substrate (achiral) substrate (achiral) chiral catalyst chiral catalyst product (chiral) chiral catalyst product (chiral) • Chiral catalysis - ideally a reagent that accelerates a reaction (without being destroyed) in a chiral environment thus permitting one chiral molecule to generate millions of new chiral molecules... 123.702 Organic Chemistry 13 Catalytic enantioselective reduction OMe O CBS catalyst (10%) MeO H OH BH3•THF MeO MeO 93% ee • An efficient catalyst for the reduction of ketones is Corey-Bakshi-Shibata catalyst (CBS) • This catalyst brings a ketone and borane together in a chiral environment • The reagent is prepared from a proline derivative • The reaction utilises ~10% heterocycle and a stoichiometric amount of borane and works most effectively if there is a big difference between each of the substituents on the ketone • The mechanism is quite elegant... H H Ph Ph BH3 N Ph N Ph B O H3B B O Me Me CBS catalyst active catalyst proline derivative 123.702 Organic Chemistry 14 Mechanism of CBS reduction • interaction of amine & borane activates borane • it positions the borane • it increases the Lewis acidity of the endo boron H H Ph Ph catalyst turnover BH3•THF N Ph N Ph B O H3B B O Me Me H OH O RL RS RL RS coordination of Ph Ph aldehyde activates aldehyde and places O Me O Me it close to the borane N B N B Ph H Ph H B B H O RS H O RS H H RL RL chair-like transition state largest substituent is pseudo-equatorial 123.702 Organic Chemistry 15 Catalytic enantioselective nucleophilic addition O H OH O (–)-DAIB (2%) O + C5H11 Zn C5H11 H C5H11 Me Me >95% ee NMe2 OH Me (–)-DAIB Me Me Me Me Me Me Me Me Me Me Me N C H N C H N 5 11 5 11 Me Zn Zn O vs. O O Zn C H Ar H 5 11 Me O Me O Me Zn Zn Zn C H 5 11 C5H11 C5H11 C5H11 H Ar C4H9 C4H9 disfavoured • There are now many different methods for catalytic enantioselective reactions • Here are just a few examples... • Many simple amino alcohols are known to catalyse the addition of dialkylzinc reagents to aldehydes • Mechanism is thought to be bifunctional - one zinc becomes the Lewis acidic centre and activates the aldehyde • The second equivalent of the zinc reagent actually attacks the aldehyde • Once again a 6-membered ring is involved and 1,3-diaxial interactions govern selectivity 123.702 Organic Chemistry 16 Lewis acid catalysed allylation / crotylation (R)-BINAP, AgOTf OH Ph O E Ph R SSnnBBuu33 THF, —20°C P + Me SnBu3 Ph P Ph H MReZ Ph Me Ph E:Z 95:5 56% 70%de 94%ee E:Z 2:98 72% 70%de 91%ee E:Z 53:47 45% 70%de 94%ee • Chiral Lewis acids can be used to activate carbonyl group with impressive results • Allylation works very well with high e.e.
Load more

Recommended publications
  • Experiment 4
    Experiment Limiting Reactant 5 A limiting reactant is the reagent that is completely consumed during a chemical reaction. Once this reagent is consumed the reaction stops. An excess reagent is the reactant that is left over once the limiting reagent is consumed. The maximum theoretical yield of a chemical reaction is dependent upon the limiting reagent thus the one that produces the least amount of product is the limiting reagent. For example, if a 2.00 g sample of ammonia is mixed with 4.00 g of oxygen in the following reaction, use stoichiometry to determine the limiting reagent. 4NH3 + 5O2 4NO + 6H2O Since the 4.00 g of O2 produced the least amount of product, O2 is the limiting reagent. In this experiment you will be given a mixture of two ionic solids, AgNO3 and K2CrO4, that are both soluble in water. When the mixture is dissolved into water they will react to form an insoluble compound, Ag2CrO4, which can be collected and weighed. The reaction is the following: 2 AgNO3(aq) + K2CrO4(aq) Ag2CrO4(s) + 2 KNO3(aq) Colorless Yellow Red colorless Precipitate Precipitate is the term used for an insoluble solid which is produced by mixing two solutions. Often the solid particles are so fine that they will pass right through the pores of a filter. Heating the solution for a while causes the particles to clump together, a process called digesting. The precipitate coagulates upon cooling and eventually settles to the bottom of a solution container. The clear liquid above the precipitate is called the supernatant.
    [Show full text]
  • Review of Calculations for Organic Reactions (Assignment #1B)
    Review of Calculations for Organic Reactions (Assignment #1b) In your experiments the quantities of many reactants are given in mass or volume, though chemicals react in mole ratios, because it is not possible to measure a quantity in moles easily. You will have to convert mass or volume (mass = volume x density) to moles before beginning an experiment. You will also have to recognize stoichiometric relationships between reactants and products, which is based on mole ratio, in order to be able to calculate the theoretical yield of product you expect to isolate. You will apply the knowledge from this session to complete the theoretical yield calculation in your prelab reports and postlab reports. In this lab you are expected to be able to differentiate between a limiting reagent and excess reagents, solvents and catalysts which are crucial for the reaction to occur and go to completion. A limiting reagent is a reactant that has the lowest number of moles of all reactants in the chemical reaction and once it is completely consumed the reaction terminates. An excess reagent is a reactant that has a higher number of moles and therefore is not used up when a reaction goes to completion. Solvents and catalysts are not involved in the determination of limiting reagent. An example of calculations that you will be expected to perform is shown using the reaction of phenol with nitric acid. Preparation of picric acid requires the nitration of phenol. Given 5.00 grams of phenol and 15.0 mL concentrated nitric acid (15.9 M), one can determine the MAXIMUM theoretical amount of picric acid formed.
    [Show full text]
  • Chiral Auxiliaries and Optical Resolving Agents
    Chiral Auxiliaries and Optical Resolving Agents Most bioactive substances are optically active. For instance, if This brochure introduces a variety of chiral auxiliaries and a substance is synthesized as a racemic compound, its optical resolving agents. We hope that it will be useful for your enantiomer may show no activity or even undesired bioactivity. research of the synthesis of optically active compounds. Thus, methods to gain enantiopure compounds have been Additionally, TCI has some brochures introducing chiral developed. When synthesizing enantiopure compounds, the compounds for the chiral pool method in “Chiral Building Blocks”, methods are roughly divided into three methods. “Terpenes”, “Amino Acids” and other brochures. Sugar derivatives are also introduced in a catalog, “Reagents for Glyco Chemistry Chiral pool method: & Biology”, and category pages of sugar chains. Furthermore, The method using an easily available chiral compound as a TCI has many kinds of catalysts for asymmetric synthesis and starting material like an amino acid or sugar. introduce them in brochures such as “Asymmetric Synthesis” and Asymmetric synthesis: “Asymmetric Organocatalysts”, and other contents. The method to introduce an asymmetric point to compounds You can search our information through “asymmetric synthesis” without an asymmetric point. Syntheses using achiral as a keyword. auxiliaries are included here. Optical resolution: The method to separate a racemic compound into two ● Reactions with Chiral Auxiliaries enantiomers. The direct method using a chiral column and One of the most famous named reactions using chiral auxiliaries1) the indirect method to separate two enantiomers using is the Evans aldol reaction.2) This reaction is quite useful because optical resolving agents to convert into diastereomers are this reaction can efficiently introduce two asymmetric carbons into examples.
    [Show full text]
  • Page 1 of 108 RSC Advances
    RSC Advances This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. This Accepted Manuscript will be replaced by the edited, formatted and paginated article as soon as this is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/advances Page 1 of 108 RSC Advances Applications of oxazolidinones as chiral auxiliaries in the asymmetric alkylation reaction applied to total synthesis Majid M. Heravi,* Vahideh Zadsirjan, Behnaz Farajpour Department of Chemistry, School of Science, Alzahra University, Vanak, Tehran, Iran Email: [email protected] Abstract Various chiral oxazolidinones (Evans' oxazolidinones) have been employed as effective chiral auxiliaries in the asymmetric alkylation of different enolates. This strategy has been found promising and successful when used as key step (steps) in the total synthesis of several biologically active natural products. In this report, we try to underscore the applications of Manuscript oxazolidinones as chiral auxiliary in asymmetric alkylation, and particularly in crucial chiral inducing steps in the total synthesis of natural products, showing biological activities.
    [Show full text]
  • Photoremovable Protecting Groups Used for the Caging of Biomolecules
    1 1 Photoremovable Protecting Groups Used for the Caging of Biomolecules 1.1 2-Nitrobenzyl and 7-Nitroindoline Derivatives John E.T. Corrie 1.1.1 Introduction 1.1.1.1 Preamble and Scope of the Review This chapter covers developments with 2-nitrobenzyl (and substituted variants) and 7-nitroindoline caging groups over the decade from 1993, when the author last reviewed the topic [1]. Other reviews covered parts of the field at a similar date [2, 3], and more recent coverage is also available [4–6]. This chapter is not an exhaustive review of every instance of the subject cages, and its principal focus is on the chemistry of synthesis and photocleavage. Applications of indi- vidual compounds are only briefly discussed, usually when needed to put the work into context. The balance between the two cage types is heavily slanted to- ward the 2-nitrobenzyls, since work with 7-nitroindoline cages dates essentially from 1999 (see Section 1.1.3.2), while the 2-nitrobenzyl type has been in use for 25 years, from the introduction of caged ATP 1 (Scheme 1.1.1) by Kaplan and co-workers [7] in 1978. Scheme 1.1.1 Overall photolysis reaction of NPE-caged ATP 1. Dynamic Studies in Biology. Edited by M. Goeldner, R. Givens Copyright © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30783-4 2 1 Photoremovable Protecting Groups Used for the Caging of Biomolecules 1.1.1.2 Historical Perspective The pioneering work of Kaplan et al. [7], although preceded by other examples of 2-nitrobenzyl photolysis in synthetic organic chemistry, was the first to apply this to a biological problem, the erythrocytic Na:K ion pump.
    [Show full text]
  • Chapter 8. Chiral Catalysts José M
    Chapter 8. Chiral Catalysts José M. Fraile, José I. García, José A. Mayoral 1. The Origin of Enantioselectivity in Catalytic Processes: the Nanoscale of Enantioselective Catalysis. Enantiomerically pure compounds are extremely important in fields such as medicine and pharmacy, nutrition, or materials with optical properties. Among the different methods to obtain enantiomerically pure compounds, asymmetric catalysis1 is probably the most interesting and challenging, in fact one single molecule of chiral catalyst can transfer its chiral information to thousands or even millions of new chiral molecules. Enantioselective reactions are the result of the competition between different possible diastereomeric reaction pathways, through diastereomeric transition states, when the prochiral substrate complexed to the chiral catalyst reacts with the corresponding reagent. The efficiency of the chirality transfer, measured as enantiomeric excess [% ee = (R−S)/(R+S) × 100], depends on electronic and steric factors in a very subtle form. A simple calculation shows that differences in energy of only 2 kcal/mol between these transition states are enough to obtain more than 90% ee, and small changes in any of the participants in the catalytic process can modify significantly this difference in energy. Those modifications may occur in the near environment of the catalytic centre, at less than 1 nm scale, but also at longer distances in the catalyst, substrate, reagent, solvent, or support in the case of immobilized catalysts. This is the reason because asymmetric
    [Show full text]
  • Protein Measurement with the Folin Phenol Reagent*
    PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT* BY OLIVER H. LOWRY, NIRA J. ROSEBROUGH, A. LEWIS FARR, AND ROSE J. RANDALL (From the Department of Pharmacology, Washington University School oj Medicine, St. Louis, Missouri) (Received for publication, May 28, 1951) Since 1922 when Wu proposed the use of the Folin phenol reagent for Downloaded from the measurement of proteins (l), a number of modified analytical pro- cedures ut.ilizing this reagent have been reported for the determination of proteins in serum (2-G), in antigen-antibody precipitates (7-9), and in insulin (10). Although the reagent would seem to be recommended by its great sen- sitivity and the simplicity of procedure possible with its use, it has not www.jbc.org found great favor for general biochemical purposes. In the belief that this reagent, nevertheless, has considerable merit for certain application, but that its peculiarities and limitations need to be at Washington University on June 25, 2009 understood for its fullest exploitation, it has been studied with regard t.o effects of variations in pH, time of reaction, and concentration of react- ants, permissible levels of reagents commonly used in handling proteins, and interfering subst.ances. Procedures are described for measuring pro- tein in solution or after precipitation wit,h acids or other agents, and for the determination of as little as 0.2 y of protein. Method Reagents-Reagent A, 2 per cent N&OX in 0.10 N NaOH. Reagent B, 0.5 per cent CuS04.5Hz0 in 1 per cent sodium or potassium tartrabe. Reagent C, alkaline copper solution.
    [Show full text]
  • Biochemistry Panel Plus
    Piccolo® BioChemistry Panel Plus For In Vitro Diagnostic Use and Professional Use Only Customer and Technical Service: 1-800-822-2947 Customers outside the US: +49 6155 780 210 Abaxis, Inc. ABAXIS Europe GmbH 3240 Whipple Rd. Bunsenstr. 9-11 Union City, CA 94587 64347 Griesheim USA Germany 1. Intended Use The Piccolo® BioChemistry Panel Plus, used with the Piccolo Xpress® chemistry analyzer, is intended to be used for the in vitro quantitative determination of alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), amylase, aspartate aminotransferase (AST), c-reactive protein (CRP), calcium, creatinine, gamma glutamyltransferase (GGT), glucose, total protein, blood urea nitrogen (BUN), and uric acid in lithium heparinized whole blood, lithium heparinized plasma, or serum in a clinical laboratory setting or point-of-care location. The Abaxis CRP method is not intended for high sensitivity CRP measurement. 2. Summary and Explanation of Tests The Piccolo BioChemistry Panel Plus and the Piccolo Xpress chemistry analyzer comprise an in vitro diagnostic system that aids the physician in diagnosing the following disorders. Alanine aminotransferase (ALT): Liver diseases, including viral hepatitis and cirrhosis. Albumin: Liver and kidney diseases. Alkaline phosphatase (ALP): Liver, bone, parathyroid, and intestinal diseases. Amylase: Pancreatitis. Aspartate aminotransferase (AST): Liver disease including hepatitis and viral jaundice, shock. C-Reactive Protein (CRP): Infection, tissue injury, and inflammatory disorders. Calcium: Parathyroid, bone and chronic renal diseases; tetany. Creatinine: Renal disease and monitoring of renal dialysis. Gamma glutamyltransferase (GGT): Liver diseases, including alcoholic cirrhosis and primary and secondary liver tumors. Glucose: Carbohydrate metabolism disorders, including adult and juvenile diabetes mellitus and hypoglycemia. Total protein: Liver, kidney, bone marrow diseases; metabolic and nutritional disorders.
    [Show full text]
  • APPLICATIONS in ASYMMETRIC SYNTHESIS Carlos
    324 SYNTHESIS OF OCTAHYDROBENZO - 1, 2,3 - DIAZAPHOSPHOLIDINE - 2 - OXIDES AND THEIR DERIVATIVES: APPLICATIONS IN ASYMMETRIC SYNTHESIS DOI: http://dx.medra.org/ 10.17374/targets.2020.23.324 Carlos Cruz - Hernández a , José M. Landeros a , Eusebio Juaristi * a,b a Departamento de Química, Centro de Investigación y de E studios Avanzados, Avenida IPN 2508, 07360 Ciudad de México, Mexico b El Colegio Nacional, Luis González Obregón 23, Centro Histórico, 06020 Ciudad de México, Mexico (e - mail: [email protected]; [email protected]) Abstract. This chapter outlines recent efforts devoted to the synthesis of heterocycles that include the octahydrobenzo - 1,3,2 - diazaphospholidine - 2 - oxide fragment, as well as their application in asymmetri c synthesis. The first part of this review provides a brief discussion of the general structural characteristics of this phosphorus - containing heterocyclic scaffold. The second part describes the synthetic paths that were undertaken to synthesize the desir ed heterocycles , as well as some relevant considerations pertaining the spectroscopic characterization of the phosphorus - containing heterocycles of interest . The third part provides several illustrative examples where the novel chiral heterocycles were employed in ena ntioselective synthesis. The new phosphorus - containing heterocycles proved useful : i) as chiral auxiliaries in nucleophilic addition reactions, as well as as imine activators in electrophilic addition reactions; ii ) as c hiral ligands i n nucleophilic allylation and crotonylation of prochiral aldehydes , and iii) as c hiral organocatalysts in enantioselective aldol, Michael, and cascade reactions. Contents 1. Introduction 2. Synthesis of the octahydrobenzo - 1,3,2 - diazaphospho lidine - 2 - oxide s 2.1 . Conformational and configurational assignments 3 .
    [Show full text]
  • Application of Chiral Sulfoxides in Asymmetric Synthesis
    MOJ Bioorganic & Organic Chemistry Review Article Open Access Application of chiral sulfoxides in asymmetric synthesis Abstract Volume 2 Issue 2 - 2018 Chiral sulfoxides are used as a toolbox for the synthesis of enantiomeric/diastereomeric compounds, which are used as precursors for the pharmaceutically/chemically Ganapathy Subramanian Sankaran,1 important molecules. The current review focuses on applying these chiral sulfoxides Srinivasan Arumugan,2 Sivaraman towards the synthesis of the compounds having stereogenic center. In general, the 3 stereogenic center induced by the sulfoxide is able to direct the stereochemistry of Balasubramaniam 1University of Massachusetts Medical School, USA further transformation necessary to complete the total synthesis of bioactive molecules. 2Department of Science and Humanity (Chemistry), Karunya The nature of the reactive conformation of the sulfoxide is strongly dependent on the Institute of Technology and Sciences, India nature of the substituents at C-α and/or C-β. 3Indian Institute of Technology Madras, Chennai, India Correspondence: Sivaraman Balasubramaniam, Senior Research Scientist, Indian Institute of Technology Madras, Chennai, India, Tel +9177 1880 5113, Email [email protected] Received: March 07, 2018 | Published: March 29, 2018 Introduction occurred in a further oxidation step of one of the sulfinyl enantiomer to sulfone.13 The titanium-binaphthol complex catalyzes not only the Over the last three decades, the sulfinyl group has received asymmetric oxidation but also the kinetic
    [Show full text]
  • Chemical Redox Agents for Organometallic Chemistry
    Chem. Rev. 1996, 96, 877−910 877 Chemical Redox Agents for Organometallic Chemistry Neil G. Connelly*,† and William E. Geiger*,‡ School of Chemistry, University of Bristol, U.K., and Department of Chemistry, University of Vermont, Burlington, Vermont 05405-0125 Received October 3, 1995 (Revised Manuscript Received January 9, 1996) Contents I. Introduction 877 A. Scope of the Review 877 B. Benefits of Redox Agents: Comparison with 878 Electrochemical Methods 1. Advantages of Chemical Redox Agents 878 2. Disadvantages of Chemical Redox Agents 879 C. Potentials in Nonaqueous Solvents 879 D. Reversible vs Irreversible ET Reagents 879 E. Categorization of Reagent Strength 881 II. Oxidants 881 A. Inorganic 881 1. Metal and Metal Complex Oxidants 881 2. Main Group Oxidants 887 B. Organic 891 The authors (Bill Geiger, left; Neil Connelly, right) have been at the forefront of organometallic electrochemistry for more than 20 years and have had 1. Radical Cations 891 a long-standing and fruitful collaboration. 2. Carbocations 893 3. Cyanocarbons and Related Electron-Rich 894 Neil Connelly took his B.Sc. (1966) and Ph.D. (1969, under the direction Compounds of Jon McCleverty) degrees at the University of Sheffield, U.K. Post- 4. Quinones 895 doctoral work at the Universities of Wisconsin (with Lawrence F. Dahl) 5. Other Organic Oxidants 896 and Cambridge (with Brian Johnson and Jack Lewis) was followed by an appointment at the University of Bristol (Lectureship, 1971; D.Sc. degree, III. Reductants 896 1973; Readership 1975). His research interests are centered on synthetic A. Inorganic 896 and structural studies of redox-active organometallic and coordination 1.
    [Show full text]
  • Asymmetric Synthesis
    Chapter 45 — Asymmetric synthesis - Pure enantiomers from Nature: the chiral pool and chiral induction - Asymmetric synthesis: chiral auxiliaries Enolate alkylation Aldol reaction - Enantiomeric excess (ee) - Asymmetric synthesis: chiral reagents and catalysts CBS reagent for chiral reductions Sharpless asymmetric epoxidation Synthesizing pure enantiomers starting from Nature’s chiral pool AcO OH HO B O O HO – O O HO + O N OH H3N OH HO OH O H … AcO HO OH O OH Sulcatol - insect pheremone HO Synthesis from the chiral pool — chiral induction turns one stereocenter into many 40 steps Me HO H Me H O O OH O O OBn O * * Only one H O HO chiral reagent H H Me OBn Me Deoxyribose Fragment of Brevetoxin B Asymmetric synthesis 1. Producing a new stereogenic centre on an achiral molecule makes two enantiomeric transition states of equal energy… and therefore two enantiomeric products in equal amounts. O O 1 1 Nu R R2 R R2 Nu E OH OH 1 O 1 Nu R R Nu R2 R2 1 R R2 O Ph OH HO Ph PhLi + N N N Asymmetric synthesis 2. O 1 R R* Nu When there is an existing O chiral centre, the two possible TS’s are diastereomeric and E 1 Nu R R* can be of different energy. Thus one isomer of the new stereogenic centre can be OH O OH produced in a larger amount. 1 1 R Nu Nu R *R 1 R* R R* HO Ph O O O Ph OH PhLi PhLi Ph Ph N N N N N Ph N N N N N OH Ph O O O Ph OH Ph A removable chiral centre… synthesis with chiral auxiliaries O ??? O R R 1) Add a chiral 3) Remove the auxiliary chiral auxiliary O O R* R* 2) Add the new stereocentre via chiral induction Enantiopure oxazolidinones as chiral auxiliaries 1.
    [Show full text]