Six-Membered Rings Diels-Alder Reactions

Reactions with Cyclic Transition states 1. Six-Membered Rings Diels-Alder Reactions 

3//-Pyrazoles 14, having R2, and sometimes also R1, as electron-withdrawing substituents, act as dienophiles at the C=C double bond. Thus with cyclopentadiene high yields of mixed endo (180) and exo (181) 

Compounds 98 behave as 1,3-dipoles in cycloaddition reactions with DMAD, ethyl cyanoformate, and alkenes the structure of the adduct 186 from ethyl cyanoformate suggests that reaction is via form 98b.131 

Cycloaddition reactions of 3/f-pyrazoIe A/-oxides do not appear to have been studied. 

Dietrich-Buchecker, D. Martina, and M. Franck-Neumann, J. Chem. Res., Synop., 78 (1978) J. Chem. Res., Miniprint, 1014 (1978). 

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In [4 + 2]-cycloadditions the diene reacts in the cisoid conformation,530 which is essential for p-orbital overlapping in the diene and the dienophile and to form the new double bond in the six-membered ring. Diels-Alder reactions are regioselec-tive. Of the two possible isomers formed in the cycloaddition of nonsymmmetri-cally substituted reactants [Eq. (6.87)], usually one predominates depending on the structure of the reacting molecules and reaction conditions ... 

Formation of six-membered rings - Diels-Alder Reactions [245, 246]... 

SYNTHESIS OF SIX-MEMBERED RINGS (DIELS-ALDER REACTION)... 

First, draw the diene and dienophile so that each molecule is properly aligned to form a six-membered ring. Then complete the reaction to form the six-membered ring Diels-Alder adduct. 

Six-membered Rings.—Diels-Alder cyclizations using heterodienophiles provide a useful route to 1,2-thiazine derivatives immonium salts (300) derived from 7V-sulphinylmethylamine react across the N=S grouping. 1,3-Thiazinones are prepared " by reaction of thia-acylisocyanates (301) with enamines and enol ethers, and the formation of this ring system is also possible by reaction of JV-monosubstituted dithiocarbamates with a,/8-unsaturated acid chlorides. The reaction involves a series of equilibria, N- to S-transacylation, and cyclization reactions. 

The Diels-Alder reaction (Figure 7.1) is of great value in synthetic organic chemistry. It is a [4 -I- 2] cycloaddition in which a diene (4-tt component) reacts with a dienophile (2-tt component) to provide a six-membered ring. In the reaction six new stereocenters are formed in a single step. The reaction is stereospecific and the absolute configuration of the newly formed asymmetric centers can be controlled efficiently. 

The Diels-Alder (DA) reaction is a pericyclic [4 -I- 2]-cycloaddition reaction where a 47t electron system (a diene) reacts with a 2jt electron system (a dienophile), yielding a new six-membered ring product. The reaction is stereospecific, where the stereochemistry of the starting compounds is preserved in the products. In a DA reaction with normal electron demand, the dienophile typically bears an electron withdrawing substituent, while the diene is electron-rich. The case of the reverse situation, where an electron-poor diene reacts with an electron-rich dienophile, is known as the Diels-Alder reaction with inverse electron demand. 

In the Diels-Alder reaction (in older literature referred to as the diene synthesis ) a six-membered ring is fonned through fusion of a four-tt component, usually a diene and a two-7C component, which is commonly referred to as the dienophile (Scheme 1.1). 

We must next disconnect the six-membered ring and the only way we know to set up these chiral centres specifically is by the Diels-Alder reaction. Two alternative sites for the double bond are possible if we convert our NHi to give the necessary activating group (NOi)... 

Isoprene is highly reactive both as a diene and through its allyhc hydrogens, and its reactions are similar to those of butadiene (qv) (8). Apart from polymerisation, the most widely investigated isoprene reactions are the formation of six-membered rings by the Diels-Alder reaction ... 

Just as in the Diels-Alder reaction, 1,4-dipolar cycloadditions lead to six-membered rings. Their principal use in five-membered heterocycles is for ring annulations giving [5,6] ring-fused systems. 

Ring expansion of five- to six-membered rings such as oxazole —> pyridine derivatives via a Diels-Alder reaction is a well-established procedure. However, the conversion of a six-membered heterocycle into a five-membered ring system has not been exploited to any great extent, and those systems that have been studied usually involve a cationic species. 

Diels-Alder reactions, 4, 842 flash vapour phase pyrolysis, 4, 846 reactions with 6-dimethylaminofuKenov, 4, 844 reactions with JV,n-diphenylnitrone, 4, 841 reactions with mesitonitrile oxide, 4, 841 structure, 4, 715, 725 synthesis, 4, 725, 767-769, 930 theoretical methods, 4, 3 tricarbonyl iron complexes, 4, 847 dipole moments, 4, 716 n-directing effect, 4, 44 2,5-disubstituted synthesis, 4, 116-117 from l,3-dithiolylium-4-olates, 6, 826 electrocyclization, 4, 748-750 electron bombardment, 4, 739 electronic deformation, 4, 722-723 electronic structure, 4, 715 electrophilic substitution, 4, 43, 44, 717-719, 751 directing effects, 4, 752-753 fluorescence spectra, 4, 735-736 fluorinated derivatives, 4, 679 H NMR, 4, 731 Friedel-Crafts acylation, 4, 777 with fused six-membered heterocyclic rings, 4, 973-1036 fused small rings structure, 4, 720-721 gas phase UV spectrum, 4, 734 H NMR, 4, 7, 728-731, 939 solvent effects, 4, 730 substituent constants, 4, 731 halo... 

Dipolar cycloaddUions. Interest in 1,3-dipolar cycloadditions increased dramatically during the past 20 years, largely because of the pioneering studies of Huisgen [7, 2] The versatility of this class of pericychc reactions in the synthesis of five-membered-ring heterocyclic compounds is comparable with that of the Diels-Alder reaction in the synthesis of six-membered-ring carbocyclic systems (equation 1)... 

The Diels-Alder reaction,is a cycloaddition reaction of a conjugated diene with a double or triple bond (the dienophile) it is one of the most important reactions in organic chemistry. For instance an electron-rich diene 1 reacts with an electron-poor dienophile 2 (e.g. an alkene bearing an electron-withdrawing substituent Z) to yield the unsaturated six-membered ring product 3. An illustrative example is the reaction of butadiene 1 with maleic anhydride 4 ... 

The Diels-Alder reaction is of wide scope. Not all the atoms involved in ring formation have to be carbon atoms the hetero-Diels-Alder reaction involving one or more heteroatom centers can be used for the synthesis of six-membered heterocycles. The reverse of the Diels-Alder reaction—the retro-Diels-Alder reaction —also is of interest as a synthetic method. Moreover and most importantly the usefulness of the Diels-Alder reaction is based on its 5y -stereospecifi-city, with respect to the dienophile as well as the diene, and its predictable regio-and c ifo-selectivities. °... 

The Diels-Alder reaction with triple bond dienophiles gives access to cyclo-hexa-1,4-diene derivatives. Further reaction of a reactive intermediate thus produced or a subsequent oxidation step can then lead to a six-membered ring aromatic target molecule. 

The Diels-Alder reaction is the most important method for the construction of six-membered rings. For example it can be used as a step in a benzo-anellation procedure. The experimental procedure is simple, and yields are generally good side reactions play only a minor role. 

The Diels-Alder cycloaddition is the best-known organic reaction that is widely used to construct, in a regio- and stereo-controlled way, a six-membered ring with up to four stereogenic centers. With the potential of forming carbon-carbon, carbon-heteroatom and heteroatom-heteroatom bonds, the reaction is a versatile synthetic tool for constructing simple and complex molecules [1], Scheme 1.1 illustrates two examples the synthesis of a small molecule such as the tricyclic compound 1 by intermolecular Diels-Alder reaction [2] and the construction of a complex compound, like 2, which is the key intermediate in the synthesis of (-)chlorothricolide 3, by a combination of an intermolecular and an intramolecular Diels-Alder cycloaddition [3]. 

The reaction is classified as a [ 4, + 2 ] cycloaddition 4 and 2 identify both the number of n electrons involved in the electronic rearrangement and the number of atoms originating the unsaturated six-membered ring. The subscript 5 indicates that the reaction takes place suprafacially on both components. There are other [ 4j + 2j] reactions, and therefore it is the term Diels-Alder which specifies this particular type of reaction. 

The retro Diels-Alder reaction is strongly accelerated when an oxide anion substituent is incorporated at positions 1 and 2 of the six-membered ring which has to be cycloreversed, namely at one terminus carbon of the original diene or at one sp carbon of the dienophile [51] (Equation 1.22). 

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