Diels Alder Reaction
The Diels-Alder reaction is a chemical reaction between a conjugated diene and a substituted alkene, resulting in the formation of a six-membered ring. It is a highly efficient and versatile method for constructing cyclic compounds in organic synthesis. The reaction is characterized by its regioselectivity and stereoselectivity, making it a valuable tool for creating complex molecular structures.
7 Key excerpts on "Diels Alder Reaction"
eBook - ePub- Greg T. Hermanson(Author)
- 2013(Publication Date)
- Academic Press(Publisher)
...Thus, the ultimate application of bioorthogonal chemoselective ligation is to label specifically the molecules of life directly within living systems and without cross-reactions with other biological functional groups. For a review on the use of chemoselective reactions in living systems, see Prescher and Bertozzi (2005), as well as van Berkel et al. (2011). 1 Diels–Alder Reagent Pairs The Diels–Alder reaction has long been a staple for forming carbon–carbon bonds in organic synthesis (Smith and March, 2007). The typical reaction proceeds through the 2+4 cycloaddition of a double bond (alkene) and a diene to give a six-member ring product. The double-bond reactant is often called a dienophile, and electron-withdrawing constituents next to the alkene are used to accelerate the reaction (such as COOH, CHO, and COR groups, among others). Conversely, electron-donating groups on the diene are important for increasing reaction rates (Figure 17.1). Figure 17.1 A general Diels Alder Reaction consists of a 4+2 cycloaddition between a diene and an alkene, often called a dienophile. The reaction rate and yield increase if the diene contains an electron donating group and the alkene contains an electron withdrawing group. Some reports indicated that the Diels–Alder reaction could be done in aqueous environments with a potential for accelerated reaction rates under the right conditions (Rideout and Breslow, 1980 ; Blokzijl and Engberts, 1992 ; Pai and Smith, 1995 ; Otto et al., 1996 ; Wijnen and Engberts, 1997), and the addition of InCl 3 was determined to act as a catalyst in aqueous environments (Loh et al., 1996)...
eBook - ePub- Michael North(Author)
- 2017(Publication Date)
- CRC Press(Publisher)
...The basic Diels–Alder reaction is shown in Scheme 9.30. As was discussed in section 9.2.1, during a chemical reaction the electrons in the HOMO of the nucleophile interact with the LUMO of the electrophile. For a cycloaddition reaction, it does not matter which of the two species is considered as the electrophile and which as the nucleophile although, in practice, most Diels–Alder reactions are carried out on systems containing an electron deficient alkene which is best considered as the electrophile, and an electron rich diene which is considered as the nucleophile. The key orbitals which then need to be considered are the LUMO of the alkene and the HOMO of the diene. Scheme 9.29 Scheme 9.30 Both components of a Diels–Alder reaction contain π -bonds and, in such systems, the HOMO will always be a π -orbital and the LUMO a π * -orbital. Molecular orbital diagrams of the π and π * molecular orbitals of both ethene and butadiene are shown in Figure 9.4, where the HOMO and LUMOs are indicated. For a Diels–Alder reaction (or any other cycloaddition reaction) to take place, there must be a bonding interaction between the LUMO of the alkene and the HOMO of the diene at each atom where a new bond is being formed. Another way of saying this is that the lobes of the HOMO and LUMO which overlap to form the new σ -bonds must have the same phase, the phase being indicated by the shading of the orbitals. As can be seen in Figure 9.5, this is possible for a Diels–Alder reaction provided that the reaction is a syn addition with respect to both the alkene and the diene. Such a reaction is said to be suprafacial, a term which means that both new bonds are formed using lobes of orbitals on the same face of the reactant. Thus the Diels–Alder reaction is suprafacial with respect to both components. The opposite of suprafacial is antarafacial, which implies that the new bonds are formed using the lobes of an orbital on opposite faces of a molecule...
eBook - ePubWhat's Cooking in Chemistry?
How Leading Chemists Succeed in the Kitchen
- Hubertus P. Bell, Tim Feuerstein, Carlos E. Güntner, Sören Hölsken, Jan Klaas Lohmann(Authors)
- 2011(Publication Date)
- Wiley-VCH(Publisher)
...Over the last two decades, reaction methodology directed towards achieving absolute stereocontrol in carbon-carbon bond-forming reactions has been one of the central topics that have been developed in his laboratory. In the early 1980s the diastereoselective addition of chiral enolates to aldehydes was developed by Evans and coworkers (Fig. 1, J. Am. Chem.Soc. 1981, 1 03, 2127). Figure 1. Diastereoselective addition of enolates to aldehydes. Using chiral-pool auxiliaries, this reaction is not limited to aldol additions: chiral enolates can also be alkylated with several electrophiles (Fig. 2). Figure 2. Alkylation of chiral enolates. This synthetic method has been established in the total synthesis of several natural products such as discodermolide (Fig. 3) and is known as the Evans aldol reaction (Evans-alkylation). Figure 3. Discodermolide. A more recent synthetic aspect is developing chiral catalysts for enantioselective catalysis: copper bisoxazoline complexes catalyze the enantioselective addition of silylthioketene-acetals to benzyloxyacetaldehyde in high yields and with excellent enantioselectivity (Fig. 4, J. Am. Chem.Soc. 1 997, 119,7893). Figure 4. Enantioselective addition of silylketeneacetals. Such complexes catalyze a great variety of organic transformations: depending on the metal (e.g., Cu, Sn), the oxidation state, and the counter-ion (OTf, Cl, SBF 6), many transformations are catalyzed, e.g., Diels-Alder reactions, cyclopropanations, and Michael -additions. Brunswick Stew (Lonely Soup) Starting materials (serves 4): I large chicken 4-5 stalks celery-chopped I large onion-chopped I large can (900 g) crushed tomatoes I large package frozen corn I small can (200 g) creamed corn I large package frozen baby lima beans 2 tsp sugar and salt to taste fresh ground pepper and Tabasco sauce (amount depends on who is going to eat it) Boil one large frying chicken in ca. 1.5 qt water for 1 hour; remove, cool, and debone...
eBook - ePubApplied Biocatalysis
Volume 1
- Harvey W. Blanch, Douglas S. Clark, Harvey W. Blanch, Douglas S. Clark(Authors)
- 2021(Publication Date)
- CRC Press(Publisher)
...3 Applications of Enzymatic Aldol Reactions in Organic Synthesis Mark David Bednarski Department of Chemistry, University of California at Berkeley, Berkeley, California INTRODUCTION The development of methods for the stereoselective formation of carbon-carbon bonds using the aldol reaction is a current topic of interest in organic synthesis [ 1 – 6 ]. Many successful strategies rely on chiral auxiliaries [ 7 – 15 ], and a few examples exist that use organometallic [ 16 – 19 ] catalysts. The use of enzymes in synthetic organic chemistry is only now being explored [ 20 – 41 ]. This chapter discusses the utility of readily available carbon-carbon bond forming enzymes as catalysts for the asymmetric aldol reaction. ENZYMES THAT FORM CARBON-CARBON BONDS Three general types of enzymes have been applied for the formation of carbon-carbon bonds in organic synthesis: aldolases, synthetases, and transketolases. Aldolases are a class of enzymes that catalyze the stereoselective construction and degradation of carbon-carbon bonds in monosaccharides [ 42 – 46 ]. Synthetases catalyze an irreversible aldol reaction of activated enols such as phosphoenolpyruvate (PEP) with aldoses to form complex monosaccharides [ 47 ]; transketolases catalyze the transfer of a hydroxyketo group of a keto sugar to an aldose [ 48 ]. These enzymes are discussed individually below, with an outline of their use in organic synthesis. d-FRUCTOSE-1,6,-DIPHOSPHATE ALDOLASE (FDP) d-Fructose-1,6-diphosphate (FDP) aldolase from rabbit muscle (E. C. 4.1.2.13) catalyzes the equilibrium condensation of dihydroxyacetone phosphate (1) (DHAP) with d-glyceraldehyde-3-phosphate (2) (G-3-P) to form dfructose-1, 6-biphosphate (3) (FDP) (Scheme 1) [ 42 – 44 ]. The equilibrium constant for this reaction is K = 10 4 M-1 in favor of the formation of FDP. The stereoselectivity of the reaction is absolute; the configuration of the vicinal diols at C-3′ and C-4 is always threo (i.e. d -glycero)...
- Ahindra Nag, Ahindra Nag(Authors)
- 2018(Publication Date)
- CRC Press(Publisher)
...Then, the naphthyl group of the catalyst shields the bottom face of the alkyne (Figure 11.13). FIGURE 11.13 Formal Diels–Alder/Michael addition organocascade reaction. Once the formal Diels–Alder took place, the cycloadduct 79 undergoes an easy β-elimination of the methyl selenide to render the unsaturated iminium ion 80. Next, the pendant BOC imine reacts with the double bond via a Michael addition to furnish the cis-fused bicyclic ring. After hydrolysis, the tetracyclic ring 72 was obtained with good yield and excellent enantioselectivity (82% yield, 97% ee). Decarbonylation using Wilkinson’s catalyst and treatment with phosgene and methanol introduce the carbomethoxy group at the dienamine position. Next, treatment with DIBAL-H reduces the unsaturated enamine to install the tertiary indoline stereocenter and provides the unsaturated ester. Finally, the treatment with trifluoroacetic acid deprotects the BOC amine and generates compound 85 (Scheme 11.18). SCHEME 11.18 Synthesis of compound 85. Intermediate 85 was converted into the vinyl iodide 87 using a two-step protocol. First, an allylation with allylbromide takes place, followed by reduction with DIBAL-H to furnish the diol 87 (Scheme 11.19). SCHEME 11.19 Synthesis of compound 87. Compound 87 is then converted to the protected Wieland–Gumlich aldehyde 90 through a Jeffery–Heck cyclization sequence (Scheme 11.20). First, Pd inserts in the vinyl iodide and subsequent carbopalladation forms the six-membered ring and an alkyl palladium intermediate that undergoes a fast β-elimination to form the enol intermediate...
eBook - ePubBiochemistry
An Organic Chemistry Approach
- Michael B. Smith(Author)
- 2020(Publication Date)
- CRC Press(Publisher)
...5 Dienes and Conjugated Carbonyl Compounds in Biochemistry This chapter primarily discusses dienes and alkene–ketones, alkene–aldehydes, or alkene–esters with a particular emphasis on those molecules that are conjugated. In conjugated molecules, the π-bonds are directly connected with no intervening sp 3 atoms. Conjugated dienes react similarly to other alkenes, but due to conjugation the carbocation or radical intermediates formed from conjugated dienes are resonance-stabilized. Therefore, there are two sites of reactivity: the carbonyl as well as the C=C unit and so there are differences in product distribution when compared to simple alkenes. 5.1 Conjugated Dienes and Conjugated Carbonyl Compounds A molecule containing one π-bond as part of a C=C unit is called an alkene and when a molecule contains two π-bonds in two C=C units it is called a diene. There are three fundamental structural categories for a diene: (1) those where the C=C units are separated by sp 3 hybridized atoms, (2) those where the C=C units are connected together to form a C=C—C=C unit, and (3) those that contain two π-bonds that share an sp-hybridized atom. Dienes in category (1) are called nonconjugated dienes and an example is hexa-1,5-diene, using the standard nomenclature rules for alkenes introduced in Chapter 1. Dienes in category (2) are called conjugated dienes, illustrated by hexa-1,3-diene, which can exist as a mixture of (E,E), (E,Z), or (Z,Z)-isomers. Dienes in category (3) are 1,2-dienes and an example is buta-1,2-diene, although they have the common name of allenes. An allene is an example of a cumulative π-system, specifically a cumulative diene. Benzene is a conjugated system, but the conjugated π-bonds in a six-membered ring lead to the aromatic stability of benzene (Section 9.1) and it is not a triene. The nomenclature and identification of conjugated and nonconjugated dienes is straightforward. The chemical reactions of such compounds are more complicated...
- Ming Qiu Zhang, Min Zhi Rong(Authors)
- 2022(Publication Date)
- Wiley(Publisher)
...(2010). Synthesis and characterization of epoxy with improved thermal remendability based on Diels‐Alder reaction. Polymer International 59 : 1339–1345. 23 Utracki, L.A. (1990). Polymer Alloys and Blends. Munich: Hanser Gardner Publications. 24 Isayev, A.I. (2010). Encyclopedia of Polymer Blends: Volume 1: Fundamentals. New York: Wiley‐VCH. 25 Xu, W.B., Bao, S.P., Shen, S.J. et al. (2003). Differential scanning calorimetric study on the curing behavior of epoxy resin/diethylenetriamine/organic montmorillonite nanocomposite. Journal of Polymer Science Part B: Polymer Physics 41 : 378–386. 26 Boey, F.Y.C. and Qiang, W. (2000). Experimental modeling of the cure kinetics of an epoxy‐hexaanhydro‐4‐methylphthalicanhydride (MHHPA) system. Polymer 41 : 2081–2094. 27 Chen, X.X. (2003). Novel polymers with thermally controlled covalent cross‐linking. PhD thesis. University of California, Los Angeles. 28 Imai, Y., Itoh, H., Naka, K., and Chujo, Y. (2000). Thermally reversible IPN organic‐inorganic polymer hybrids utilizing the Diels‐Alder reaction. Macromolecules 33 : 4343–4346. 29 Gousse, C. and Gandini, A. (1999). Diels‐Alder polymerization of difurans with bismaleimides. Polymer International 48 : 723–731. 30 Watanabe, M. and Yoshie, N. (2006). Synthesis and properties of readily recyclable polymers from bisfuranic terminated poly(ethylene adipate) and multi‐maleimide linkers. Polymer 47 : 4946–4952. 31 Dewar, M.J.S. and Pierini, A.B. (1984). Mechanism of the Diels‐Alder reaction. Studies of the addition of maleic anhydride to furan and methylfurans. Journal of the American Chemical Society 106 : 203–208. 32 Isaacs, N.S. and Keating, N. (1992). The rates of a Diels–Alder reaction in liquid and supercritical carbon dioxide. Journal of the Chemical Society, Chemical Communications 12 : 876–877. 33 Goiti, E., Heatley, F., Huglin, M.B., and Rego, J.M. (2004)...
