Carbonyl compounds intramolecular cycloadditions

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

As was mentioned in Section 13.2, the [27t + 27i] photocycloaddition of alkenes is an allowed reaction according to orbital symmetry considerations. Among the most useful reactions in this categoty, from a synthetic point of view, are intramolecular [27t + 2ti] cycloadditions of dienes and intermolecular [2ti + 2ti] cycloadditions of alkenes with cyclic a, -unsaturated carbonyl compounds. These reactions will be discussed in more detail in Section 6.4 of Part B. 

Keywords carbonyl compounds, chiral dienophiles, chiral dienes, chiral catalysts, intramolecular cycloadditions, chiral Lewis acids... 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

If the mesomeric stabilization is provided by a double bond, the lithiated species is a homoenolate synthon, as shown in Scheme 44a. Reaction with an electrophile typically occurs at the y-position, yielding an enamine, which can then be hydrolyzed to a carbonyl compound. An important application of this approach is to incorporate a chiral auxiliary into the nitrogen substituents so as to effect an asymmetric synthesis. 2-AzaaUyl anions (Scheme 44b), which are generated by tin-lithium exchange, can be useful reagents for inter- and intramolecular cycloaddition reactions. ... 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

The A -l,2,3,5-thiatriazoline A-oxides (20) are stable at room temperature but are easily hydrolyzed <85TL6155>. Sulfinylamines are known to react with carbonyl compounds and so with R = CHjCOPh, R = Me, an intramolecular trapping of the carbonyl group leading to a 6-membered pyrazine might have been expected. However, even in this case, the 1,2,3,5-thiatriazole S-oxide was formed due to preferential reaction with the highly nucleophilic nitrogen over cycloaddition <86H(24)1193>. 

Intramolecular Cycloadditions of Carbonyl Ylides W. Eberbach, J. Brokatzky and H. Fritz, Angew. Chem., Int. Ed. Engl., 1980, 19, 47-48. a,(3-Unsaturated Heteroatomic Compounds in 1,3-Dipolar Addition Reactions V. A. Galishev, V. N. Chistokletov and A. A. Petrov, Russ. Chem. Rev. (Engl. Transl.), 1980, 49, 880-892. 

Dihydrofurans are valuable synthetic compounds. Nevertheless, little is known about intramolecular cycloaddition of carbonyl ylides to alkynes. In one example, alkynyl pyran-4-one (233) was cyclized to dihydrofuran (234 Scheme 69).128 Possibly this reaction proceeds via an oxidopyrylium ylide intermediate as shown. 

A review of photo-cycloadditions of dienones and quinones has been published.41 The first example of a Lewis acid-catalysed 2 + 2-cycloaddition of styrene with naphthoquinone has been reported.42 FMO methods have been used to investigate the effect of substituents on the regiochemistry of the 2 + 2-photo-cycloaddition of a, fi-unsaturated carbonyl compounds with substituted alkenes.43 Evidence has been presented for the presence of a triplet exciplex intermediate in the photo-cycloaddition of 4,4-dimethylcyclohexenone to 1,1-diphenylethylene.44 The intramolecular 2-1-2-photo-cycloaddition of 2-acyloxy-3-hexenoylcyclohexenones (26) is highly diastereo-selective yielding the tricyclic adduct (27) (Scheme 10).45... 

Most compounds studied have a carbonyl group conjugated with the benzene ring and nearly all reactions are intramolecular cycloadditions. In most cases, the alkenyl moiety is connected to the arene ring via an oxygen atom, ortho or para with respect to the carbonyl group. 

A historic method for 1,2,4-oxathiazolidine synthesis is based on 1,3-cycloaddition reactions, for example, addition of carbonyl compounds across the S-C=N groups of 5-imino-l,2,3,4-thiatriazolines <1996CHEC-II(4)453>. The thermally induced conversion of 677-1,3,5-oxathiazine A-oxides 119 in refluxing benzene results in 1,2,4-oxathiazo-lines 20 in high yields by intramolecular cyclization with extrusion of carboxaldehydes (see Section 6.03.8.2). Oxidative cyclization of A-acylthioureas 114 and iV-acylthiocarbamates 115 by Br2 gives 1,2,4-oxathiazolium hydrobromides 43 and 38, respectively (see Section 6.03.8.1). 

The photochemical cycloaddition of two different alkenes leads to multiply substituted cyclobutanes, and allows for a general access to this class of compounds. More specifically, ever since Ciamician observed the light-induced isomerization of carvone (1 —> 2) (Scheme 6.1) in 1908 [1], the inter- and intramolecular reaction between an a,(3-unsaturated carbonyl compound and an alkene has become the most intensively studied and most widely used class of [2 + 2]-photocycloaddition reactions [2-9]. 

In intermolecular PET processes, radical ions are formed either as close pairs or as free species from neutral molecules (Sch. 1) [2,6]. Most commonly, carbonyl compounds or related derivatives as for example enol ethers, cyclopropyl ketones, and siloxycyclopropanes are used for intramolecular cyclization reactions. With the exception of cycloadditions the ring-building key step is always an intramolecular bond formation. In PET... 

A major problem in the reaction of a,/3-unsaturated carbonyl compounds and alkenes proves to be the competition between hetero Diels-Alder and ene reactions. Intramolecular cycloadditions of 1,6- and 1,7-dienes with ester and cyano groups at the double bond yield the ene product nearly exclusively, but with alkylidene- and benzylidene-ketoesters and 1,3-diketones the Diels-Alder reaction is preferred under thermal conditions, however under Lewis acid catalysis also ene reactions occur [12]. 

Reactions of 3-hydrazino-l,2,4-triazin-5-one derivatives with carbonyl compounds to give triazolotriazine derivatives have been reported <03KGS1376>. Intramolecular inverse electron demand cycloadditions of 2-substituted imidazoles with various 1,2,4-triazines produced both imidazo[4,5-c]pyridines (3-deazapurines) and pyrido[3,2-[Pg.387]

The course of the intramolecular photoreaction of carbonyl compounds with electron-rich alkenyl- or aryl-substituents in the side-chain is dictated essentially by the thermodynamics of the electron-transfer step. This relationship has been intensively studied for phthalimides. When AG°et is positive, [n 2 + 2] cycloaddition reactions were observed with alkenyl substituents and classical Norrish II chemistry for aryl-substituted substrates. When AG°et was negative, electron transfer prod-... 

The simplest ylide generation method among the deprotonation route (Section II,D) consists of the condensation of N-substituted a-amino esters with carbonyl compounds. This procedure must be especially useful for utilization in intramolecular cycloadditions because the substrates for the cycloadditions are simply prepared in situ by reacting the carbonyl compounds (or secondary amines) bearing a trapping chain with secondary amines (or carbonyl compounds). 

Stable five-membered dioxametallacyclic adducts are obtained from the reaction of Group VIII metal-peroxo complexes (Rh, Ir, Pd, R) with nucleophilic ketones and electrophilic alkenes or ketones. The adducts of R02(PPh3)2 with acetone and l,l-dicyano-2-methylpropene have been characterized by X-ray crystallography. The reaction of (Ph3P)2R02 with nucleophilic ketones involves, as the major pathway, the precoordination of the carbonyl compound to the vacant axial site of platinum prior to intramolecular 1,3-dipolar cycloaddition (equation 42). ... 

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