Cycloaddition, Carbonylative

Chiral Cu(ll)-complexes ofbis-oxazolines as Lewis acids for catalyzed cycloaddition, carbonyl addition, and conjugate addition reactions 99PAC1407. 

Evans D. A., Rovis T., Johnson J. S. Chiral Copper(II) Complexes As Lewis Acids for Catalyzed Cycloaddition, Carbonyl Addition, and Conjngate Addition Reactions. Pure Appl. Chem 1999 71 1407-1415... 

Diazo, carbenoid, cyclization, dipolar-cycloaddition, carbonyl ylide, rhodium, tandem... 

Cycloadditions. Carbonyl ylides generated from 8- and fi-carbonyl-a-diazoketones undergo cycloaddition with quinones. Chemoselectivity (C=C vs. C=0) of the reaction is dependent on the solvent and catalyst. 

Keywords 1,3-Dipolar cycloaddition Carbonyl ylide Diazocarbonyl compounds Heterocyclic compounds Rhodium(II) acetate... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Allylic phosphates are used for carbonylation in the presence of amines under pressure. Carbonylation of diethyl neryl phosphate (389) affords ethyl homonerate (390), maintaining the geometric integrity of the double bond[244]. The carbonylation of allyl phosphate in the presence of the imine 392 affords the /3-lactam 393. The reaction may be explained by the formation of the ketene 391 from the acyl phosphate, and its stereoselective (2 + 2] cycloaddition to the imine 392 to give the /3-lactam 393(247],... 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Hydroxy-THISs react with electron-deficient alkynes to give nonisol-able adducts that extrude carbonyl sulfide, affording pyrroles (23). Compound 16 (X = 0) seems particularly reactive (Scheme 16) (25). The cycloaddition to benzyne yields isoindoles in low- yield. Further cyclo-addition between isoindole and benzyne leads to an iminoanthracene as the main product (Scheme 17). The cycloadducts derived from electron-deficient alkenes are stable (23, 25) unless highly strained. Thus the two adducts, 18a (R = H, R = COOMe) and 18b (R = COOMe, R = H), formed from 7, both extrude furan and COS under the reaction conditions producing the pyrroles (19. R = H or COOMe) (Scheme 18). Similarly, the cycloadduct formed between 16 (X = 0) and dimethylfumarate... 

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). 

Endo adducts are usually favored by iateractions between the double bonds of the diene and the carbonyl groups of the dienophile. As was mentioned ia the section on alkylation, the reaction of pyrrole compounds and maleic anhydride results ia a substitution at the 2-position of the pyrrole ring (34,44). Thiophene [110-02-1] forms a cycloaddition adduct with maleic anhydride but only under severe pressures and around 100°C (45). Addition of electron-withdrawiag substituents about the double bond of maleic anhydride increases rates of cycloaddition. Both a-(carbomethoxy)maleic anhydride [69327-00-0] and a-(phenylsulfonyl) maleic anhydride [120789-76-6] react with 1,3-dienes, styrenes, and vinyl ethers much faster than tetracyanoethylene [670-54-2] (46). 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

Most ozonolysis reaction products are postulated to form by the reaction of the 1,3-zwitterion with the extmded carbonyl compound in a 1,3-dipolar cycloaddition reaction to produce stable 1,2,4-trioxanes (ozonides) (17) as shown with itself (dimerization) to form cycHc diperoxides (4) or with protic solvents, such as alcohols, carboxyUc acids, etc, to form a-substituted alkyl hydroperoxides. The latter can form other peroxidic products, depending on reactants, reaction conditions, and solvent. 

The quiaones have excellent redox properties and are thus important oxidants ia laboratory and biological synthons. The presence of an extensive array of conjugated systems, especially the a,P-unsaturated ketone arrangement, allows the quiaones to participate ia a variety of reactioas. Characteristics of quiaoae reactioas iaclude nucleophilic substitutioa electrophilic, radical, and cycloaddition reactions photochemistry and normal and unusual carbonyl chemistry. 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

Photolysis of 2,3-diphenyl-A -azirine (442) generates benzonitrile ylide (443). Irradiation in the presence of ethyl cyanoformate resulted in a mixture of the oxazoline (444) and the imidazole (445) by 1,3-dlpolar cycloaddition to the carbonyl and nitrile group, respectively (72HCA919). 

Since 1,3-dipolar cycloadditions of diazomethane are HOMO (diazomethane)-LUMO (dipolarophile) controlled, enamines and ynamines with their high LUMO energies do not react (79JA3647). However, introduction of carbonyl functions into diazomethane makes the reaction feasible in these cases. Thus methyl diazoacetate and 1-diethylaminopropyne furnished the aminopyrazole (620) in high yield. 

Cycloadditions of aziridines to diphenylcyclopropenone lead to 4-oxazolines (36) (70CJC89). A mechanism involving initial addition to the cyclopropenone carbonyl group followed by ring opening and recyclization was suggested. 

IH-Azepine, 1-methoxy carbonyl-cycloaddition reactions, 7, 522 with nitrosobenzene, 7, 520 tricarbonyliron complex acylation, 7, 512-513 conformation, 7, 494 tricarbonylruthenium complex cycloaddition reactions, 7, 520 1 H-Azepine, l-methoxycarbonyl-6,7-dihydro-synthesis, 7, 507... 

Azirine, trans-2-methyl-3-phenyl-racemization, 7, 33, 34 1-Azirine, 2-phenyl-reactions, 7, 69 with carbon disulfide, S, 153 1-Azirine, 3-vinyl-rearrangements, 7, 67 Azirines, 7, 47-93 cycloaddition reactions, 7, 26 fused ring derivatives, 7, 47-93 imidazole synthesis from, 5, 487-488 photochemical addition reactions to carbonyl compounds, 7, 56 photolysis, 5, 780, 7, 28 protonated... 

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. 

In general, reaction of diazomethane with a, -unsaturated carbonyl compounds affords pyrazolines in which the nucleophilic methylene group is attached to the carbon atom of the carbonyl compound. According to Huisgen, the reactions belong to the general class of 1,3-dipolar cycloadditions. 

Fluorinated a., -unsaturated carbonyl compounds also are reactive dipo-larophiles Because ol the highly activating carbonyl substituent, these 1,3-dipolar cycloadditions are rapid and regiospecific Good examples are the additions of... 

Heterocyclic enamines often undergo two-step 1,3 cycloaddition with methyl vinyl ketone. This involves electrophilic attacks by an olefinic carbon and by a carbonyl carbon (24,25). For example, 1,2-dimethyl-Zl -pyrroline (14), when treated with methyl vinyl ketone, produces 1,6-dimethyl-2,3,4,5-tetrahydroindole (15) (24). The requirement which must be met so that this type of cyclization reaction can take place is that the a position of the heterocyclic enamine be carbon substituted. This provides... 

Olefins conjugated with electron-withdrawing groups other than a carbonyl group undergo reactions with enamines in a manner similar to the carbonyl-conjugated electrophilic alkenes described above. Namely, they condense with an enamine to form a zwitterion intermediate from which either 1,2 cycloaddition to form a cyclobutane ring or simple alkylation can take place. 

Other advances include the construction of seven- and nine-membered rings via the analogous [4-1-3] and [6-1-3] cycloadditions with dienes and trienes respectively. Heterocycles, such as tetrahydrofurans and pyrrolidines, are accessible using carbonyl compounds and imines as substrates. The following discussion is organized around these recent discoveries. It serves to illustrate the versatility and the high degree of selectivity which are some of the distinctive features of the Pd-TMM chemistry. 

Introduction of an additional methyl group on the donor atom of TMM moiety gives a low 33% yield of the perhydroindans (49, X=H2) and (50, X=H2) with substantial production of the diene by-products [24]. However, it is still remarkable that the reaction works at all since the corresponding intermolecular cycloaddition failed. Incorporation of a carbonyl moiety adjacent to the donor carbon atom doubles the yield of the cycloadducts to 66% (Scheme 2.15). This so-called acyl effect works by making the donor carbon of the TMM unit "softer," thus facilitating the initial step of the conjugate addition, as well as inhibiting base-induced side reactions [22]. 

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