Cyclization reactions 1,3-dipolar

In addition to this, asymmetric 1,3-dipolar cyclization reactions of nitrones with olefins,40 41 catalytic enantioselective cyanation of aldehydes,42 catalytic enantioselective animation,43 and aza-Michael reactions44 have been reported, and high enantioselectivities are observed. 

The 5,6-double bond in activated pyrimidines can participate in thermal [4-1-2] cyclization reactions as demonstrated by the 1,3-dipolar cycloaddition reactions of O-protected thymidine derivatives 483 with the nonstabilized azo-methine ylide 484, which is generated from trimethylamine AT-oxide by reaction with EDA <2002SC1977>. 

Condensation of the sodium salt of phenylacetonitrile with 1,3-dibromobulane gives an isomeric mixture of l-cyano-2-methyl-1-phenylcyclobutanes 21 and 22.30 The effects of solvents on this cyclization reaction have been studied. While solvents of low dielectric constants seem to favor the formation of 21, the ratio of 21 to 22 was found to be almost 1 1 in dipolar aprotic solvents, as can be seen in the following table.30... 

A very short and elegant synthesis of the 16-rtiembered dilactone ( )-pyrenophorin (515) has been accomplished by the dipolar cycloaddition reaction of a trialkylsilyl nitronate (81TL735). Nitromethane was added to 3-buten-2-one and the carbonyl group of the product reduced with sodium borohydride. The nitro alcohol (511) was converted to the acrylate (512) which was then subjected to a dimerization-cyclization reaction by treatment with chlorotrimethylsilane and triethylamine in dry benzene. Hydrogenation of the mixture of isoxazoline products (513) over palladium on charcoal followed by double dehydration of the intermediate bis-/3-hydroxyketone (514) led to ( )- and meso-pyrenophorin (Scheme... 

There is less evidence for the participation of azomethine ylides 88 in the early examples of the thermal cyclization reactions of Meldrum s acid derivatives 86. This reaction, conducted under flash vacuum pyrolysis conditions, may proceed via the methyleneketene 87. Hydrogen transfer from this highly unstable species may lead to the dipolar intermediate 88, which could cyclize either in a 6zr, to give 89, or 8tt, to give 90, manner (Scheme 27) [83JCS(CC)988 85TL833 87JCS(CC)140]. 

A 1,3-dipolar cycloaddition of indanoneenamines and nitrilimines produces the indeno[2,1 -cjpyrazole (52).135 The yields of such cyclization reactions are high (60-80%). Reactions of A-alkylpyridine-3-ylides with picryl chloride involving cyclization give a mixture of pseudoazulenes 35 and 36.103 An additional preparation of pyrindine 26 is from 1,2- and 1,4-oxides of azonine.55... 

Intermodular cyclization reactions which do not involve 1,3-dipolar cycloaddition reactions 128... 

Numerous methods of preparing bicyclic systems from monocyclic precursors have been reported and four general strategies can be identified. These are (i) intermolecular cyclization reactions which do not involve 1,3-dipolar cycloaddition reactions (ii) intermolecular 1,3-dipolar cycloaddition reactions (iii) nonoxidative intramolecular cyclizations and (iv) oxidative intramolecular cyclization reactions. These four general methodologies are now considered. 

Although in most cyclization reactions the 5(4//)-oxazolones react as 1,3-dipolar reactants (azo-methine ylides) through the mesoionic tautomers, they serve as dipolarophiles with nitrile imines <92H(34)315>. The nitrile imines, generated by the thermal decomposition of tetrazoles (82), add across the 2,3 double bond to generate triazoles (83) after further reaction (Scheme 26). Since the 5(4//)-oxazolones with a hydrogen at position 4 are in equilibrium with the 5(2//)-oxazolones under the reaction conditions, the addition of the nitrile imine also occurs across the 3,4-double bond of these compounds to afford an isomeric triazole (84). Pyrazines (85), which are products of the thermal decomposition of 5(4 0 Oxazolones <76HCA2149>, as well as diarylethylenes (86), are also formed. 

Selective synthesis and cycloaddition reactions of new azomethine imines 109 containing a 1,2,4-triazine ring have been reported. 4,5-Dihydro[l,2,4]triazolo[3,4-c]benzo[l,2,4]triazines 108 with aromatic aldehydes gave stable iminium salts which were deprotonated to give new mesomeric betaines 109. These underwent 1,3-dipolar cyclization reactions affording tetra- and pentacyclic heterocycles 110 <05EJO3553 05H1889>. 

There are numerous reviews on 1,3-dipolar cycloadditions. We will mention only those published since 1984, first of all the two-volume handbook, edited by Padwa (1984), then reviews by Drygina and Garnovskii (1986), Samuilov and Konovalov (1986), Huisgen (1988), Tsuge et al. (1989), Carruthers (1990), Padwa and Schoffstall (1990), Padwa (1991a, 1991b), Wade (1991) and Rank (1994). This extensive literature clearly demonstrates the current interest in these cyclization reactions. 

In this section we discuss first experimental data that are helpful for providing an answer to the question whether in 1,3-dipolar cycloadditions the two o bonds are formed in a concerted process, i. e., with one transition state (as shown in 6.13), or stepwise via a zwitterionic or biradical intermediate. We include investigations with dipole reagents other than diazo compounds, when appropriate or even necessary for understanding mechanistic problems in cyclization reactions of diazoalkanes. 

Diastereomeric cycloadducts are obtained when the dipole and the dipolarophile each form a chiral center in the cyclization reaction. Two different types of diastereospecificity occur in dipolar cycloadditions ... 

Thiadiazolopyridines, e.g. (32), result from the base-catalysed reaction of alkylamines with 3,4-diaroyl-thiadiazoles, e.g. (31), (Scheme 15). The yield of compound (32) is 88%, but the corresponding oxadiazolopyridine is only obtained in 13% yield. As many diaroyl-substituted five-membered heterocycles are easily obtainable from 1,3-dipolar cyclization reactions with diaroyl-alkynes, this reaction may provide a useful method for preparing fused pyridines. ... 

Carbon-carbon double bonds directly attached to indole rings have been shown to participate in cyclization reactions. The vinyl ether (395), on treatment with A -methylhydroxylamine, undergoes a 1,3-dipolar cycloaddition to the adduct (396) (Equation (110)) <85JA2569>. The intramolecular addition of a nitroalkane anion to an allylsulfinate gives a similar ergot alkaloid precursor (Equation (111)) <86TL3169>. 

Pyridines have also been used in cyclization reactions. Two noteworthy examples are shown in scheme 3. The reaction of substituted pyridine 32 with a nitrile affords imidazo[l -ajpyridine 33 in excellent yield <01JOC2862>. Oku and co-workers have reported the use of tetrahydroquinolizinium ylides in a 13-dipolar cycloaddition reaction (34- 35) <01JOC1638>. Sieburth has also published an account of the [4+4] photocyclization reaction of pyridones on route to fusicoccin <01S1185>. 

Coldham et al. reported on a cascade reaction sequences involving condensation, cyclization, intramolecular dipolar cycloaddition for preparation of fused tricyclic heterocycles which can be converted in two steps to a 1,3-oxazine present in some yuzurimine-type Daphniphyllum alkaloids under some conditions [57], In another study, addition of hydroxylamine to substituted 4-chlorobutanals gives intermediate nitrones that imdergo tandem cyclization and then intramolecular dipolar cycloaddition to give the core... 

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