Cycloaddition reactions cyclobutanones

Staudinger observed that the cycloaddition of ketenes with 1,3-dienes afforded cyclobutanones from a formal [2+2] cycloaddition [52] prior to the discovery of the Diels-Alder reaction. The 2+2 cycloadditions were classified into the symmetry-allowed 2+2 cycloaddition reactions [6, 7], It was quite momentous when Machiguchi and Yamabe reported that [4+2] cycloadducts are initial products in the reactions of diphenylketene with cyclic dienes such as cyclopentadiene (Scheme 11) [53, 54], The cyclobutanones arise by a [3, 3]-sigmatropic (Claisen) rearrangement of the initial products. 

Ketenes have cnmnlative bonds and can undergo [2+2] cycloaddition reactions across C=C and C=0 bonds. Interestingly, most of the prodncts obtained are cyclobutanones rather than oxetanes. Thermal [2+2] cycloaddition reactions in the pseudoexcitation band occur between electron donors and acceptors. Alkenes are donors while ketenes are acceptors. In contrast to the experimental observations. 

Cycloaddition reactions of ketenes with alkenes have long been known to give cyclobutanones [123] and to proceed with retention of the configurations [124], The reactions were classified into the symmetry-allowed cycloaddition reactions... 

The regiochemistry of ketene iminium salt cycloadditions can also differ from ketene cycloadditions. Whereas reaction of styrene with a series of ketene iminium salts gave 3-phenyI-cyclobutanones7 (60-70% yield) similar to the regiochemistry of ketene cycloadditions, reaction with a series of acrylates and a,/J-unsaturated ketones gave cyclobutanones 5 with regiochemistry opposite to what would be expected from electrostatic considerations of ketene cycloadditions.s... 

Reaction of an alkene with keteniminium salts resulted in [2 + 2]-cycloaddition reactions (see Section 1.3.5.3). Hydrolysis of the intermediate cyclobutanone iminium salts 3 gave the cy-clobutanone 4.- 12 316 The cyclobutanone iminium salts are usually not isolated since they hydrolyze on aqueous workup. 

There have been three reported syntheses of 1,2-diazocines by means of ring-expansive cycloaddition reactions. In the first case, Sasaki and coworkers reacted 4,4-dimethyl-3,5-diphenylisopyrazole 25 with diphe-nylcyclopropenone to obtain diazocine 26 (73SC249). The second cycloaddition was achieved by Haddadin et al., who condensed cyclobutanone with tetrazine 27 (Ar = Ph) to afford diazocine 28 (Ar = Ph, X = O) or 29, depending on whether methanolic base or diethylamine was used as catalyst (84TL2577). A similar reaction was used to prepare a triazocine see Section IV,A,1. 

The (2 + 2) cycloaddition reactions of ketenes with alkenes are synthetically useful routes to cyclobutanones. Ketenes are particularly useful due to the low steric hindrance at the carbonyl carbon. An example is the reaction of dichloro-ketene with cyclopentadiene which, after reductive dechlorination of the product, gives bicyclo[3.2.0]hept-2-en-6-one (Expt 7.25). 

No reaction occurs with vinyl ethers, silyl enol ethers, or ketene silyl acetals, usually used in thermal [2 + 2]cycloaddition reactions, but the present case is the first example of the preparation of a chiral cyclobutanone by a cycloaddition route. 

P Volume 1,1991,283 pp. 109.50/ 69.50 ISBN 1-55938-180-9 CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Brian Halton. Strain in Organic Chemistry A Perspective, Brian Halton. Gem-Dihalocyclopropanes in Chemical Synthesis, Martin G. Banwell and Monica E. Re-um. 1-Halo- and 1, 2-Dihalocyclopropenes Useful Synthetic Intermediates, Mark S. Baird. Cyciization and Cycloaddition Reactions of Cyclopropenes, Albert Padwa and Glen E. Fryx-ell. New Synthetic Pathways From Cyclobutanones, Edward Lee-Ruff. Cyclic Alkynes, Enynes and Dienynes A Synthetic Challenge, Herbert Meier. Index. 

Cycloaddition Reactions. Chiral acrylamides derived from pyrrolidines (2) or (3) undergo stereoselective [4 + 2] cycloaddition reactions with a variety of cyclic dienes. Similarly, nitroso compounds derivatized with pyrrolidine (2) and generated in situ give cycloadducts with a high degree of stereoselectivity (eq 6). Intramolecular [2 + 2] cycloadditions involving pyrrolidine-derived keteniminium salts have been shown to produce chiral cyclobutanones. ... 

The chiral titanium reagent (6) also catalyzes the [2 + 2] cycloaddition reaction of 1,3-oxazolidin-2-one derivatives of a,(3-unsaturated carboxylic acids and ketene dithioacetals in the presence of MS 4A to give cyclobutanone dithioacetal derivatives with high optical purity (eq 10). Vinyl sulfides, alkynyl sulfides, and 1,2-propadienyl sulfides can also be employed in this reaction to give the corresponding cyclobutanes, cyclobutenes and methylenecyclobutane derivatives with high optical purity (eqs 11 and 12). ... 

The ketene-alkene cycloaddition gives cyclobutanones in a thermal reaction. Most ketenes are not kinetically stable, so they are usually generated in situ, either by E2 elimination of HC1 from an acyl chloride or by a Wolff rearrangement of an a-diazoketone (see Chapter 2). 

When ketenes react with 1,3-dienes, bicyclic cyclobutanones are obtained. The mechanism of this reaction is usually described as a one-step [2 + 2] cycloaddition reaction, but the following two-step mechanism was recently proposed. 

Cychadditions. Moore and Weyler1 noted that t-butylcyanoketene (2) is unusually reactive in cycloaddition reactions. Thus it reacts with cyclohexene (3) to form the cyclobutanone (4) in 63 % isolated yield. Note that phenylcyanoketene does not react with cyclohexene.3... 

Ketenes (R2C=C=0) react at the C=C unit via thermal [2+2]-cycloaddition reactions to give cyclobutanone derivatives. Ketenes are highly electrophilic due to a low-lying LUMO (jt C=0), and the HOMO is relatively... 

Cycloaddition reactions enable easy access to four-membered rings such as yS-lactams, oxetenes, cyclobutanones, and heterocyclic compounds. Only two examples, reaction of ketenes or j5-formyl enamides with imines or alkynes, respectively, have been investigated under the action of microwaves [3j], however. These limitations could be because of the facile polymerization of ketenes. 

The fused cyclobutane derivatives produced via the above cycloaddition reactions have been utilized as synthetic precursors for the preparation of indole-2-acetonitriles (Scheme 6) [23]. First, the acetyl-substituted cyclobutanes 28 were converted to the cyclobutanone derivatives 29, which were in turn treated with hydroxylamine to provide the corresponding oximes. Beckmann fission of oximes 30 in the presence of thionyl chloride then produced the l-benzoylindole-2-aceto-nitrile derivatives 31 in good yield. 

In contrast with the photochemical cycloaddition reaction of two alkenes, the [2+2] cycloaddition of a ketene and an alkene occurs under thermal conditions. The ketene is formed typically from an acid chloride and a mild base such as EtsN, or from an a-halo-acid chloride and zinc. Cycloaddition with an alkene occurs stereospecifically, such that the geometry of the alkene is maintained in the cyclobutanone product. The regioselectivity is governed by the polarization of the alkene, with the more electron-rich end of the alkene forming a bond to the electron-deficient central carbon atom of the ketene. Thus, the product from cycloaddition of dimethylketene with the enol ether Z-171 is the cyclobutanone m-172, whereas with -171, the isomer trans-lll is formed (3.116). ... 

Cycloaddition reactions of ketenes with dienes are rapid and normally lead to the cyclobutanone product, rather than the Diels-Alder adduct. There is evidence that the cyclobutanone forms by a two-step process, involving an initial [4-1-2] cycloaddition of the diene and the ketene carbonyl group, followed by a [3,3]-Claisen rearrangement. 

DicWoroketene is particularly reactive, and reductive dechlorination of the product with zinc and acetic acid allows access to the cyclobutanone from formal addition of ketene itself. Thus, cycloaddition of dichloroketene with cyclopentadiene, followed by dechlorination and Baeyer-Villiger oxidation gave the lactone 173, a usehil precursor to various oxygenated cyclopentane products (3.117). Intramolecular cycloaddition reactions of ketenes can allow the formation of bicyclic and polycyclic products using otherwise unstable ketene intermediates. ... 

Cycloreversion Reactions A cycloreversion reaction is the reverse of a cycloaddition reaction and leads to the formation of the starting reactants through the cleavage of two bonds in the ring [18], A typical example is the formation of C2H4+ and neutral C2H4 from the cyclobutane radical cation. As shown in reaction (6.37), this reaction proceeds through the intermediacy of a distonic ion. The radical cations of a variety of other four-membered cyclic compounds, such as cyclobutanones (3), diketene (4), oxetane (5), cyclobutylamine (6), and thiocyclobutane (7), are known to participate in cycloreversion reactions [27]. 

The cycloaddition reaction of ierf-butylcyanoketene 28 with 1,3-cyclohexadiene 27 gives the cyclobutanone 29 along with some of the ether 30 (Scheme 12). This cycloaddition was found to be reversible. Cyclobutanone 29 is thermally and irreversibly transformed into the bicycHc... 

The Staudinger ketene cycloaddition is the nonphotochemical [2 + 2] cycloaddition of a ketene and an imine to form a P-lactam. Related ketene cycloaddition reactions include the cycloaddition of a keten with an olefin to afford a cyclobutanone, with a carbonyl to give a P-lactone, and with carbodiimides to form 4-imino P-lactams. 

The 2 -I- 2-cycloaddition reactions of chiral Al-alkynylated sulfoximines with ketenes afforded sulfoximine-functionalized cyclobutenes in high yields. The first examples of Lewis-acid-promoted ketene-alkene 2-i-2-cycloadditions yielded cyclobutanone cycloadducts with good yields and diastereoselectivity. " ... 

The inter- and intra-molecular formal 4 -i- 2-cycloaddition reaction between indoles and cyclobutanones was applied to the total synthesis of ( )-strictamine and ( )-aspidospermidine. The Lewis acid activation of the 3-donor-substituted cyclobutanone yielded a zwitterion intermediate that combined with the indole to produce the corresponding hydrocarazoles. The regioselectivity of the cycloaddition was controlled by the indole substituents. ... 

The use of ketene equivalents in 4- -2-cycloaddition reactions for organic synthesis has been reviewed. " a-Carbonyl ketenes behave as dienes in Diels-Alder reactions with 4-aryl-2-methyl-2,3-dihydro-l,5-benzothiadiazepines to yield regiospecific cycloadducts. The reactions of diphenylketene with cyclic ( -cw)-l,3-dienes such as cyclopentadiene and cyclohexadiene initially yield the Diels-Alder adducts, which are converted into the Staudinger cyclobutanones by [3,3]-sigmatropic rearrangementsl-Benzyl-l,3-diazabuta-l,3-dienes react with ketenes to produce the 4 - - 2-cycloadducts, substituted l-benzyl-4-(benzylidenimino)-4-phenylazetidin-2-ones, which rearrange into the more stable 5,6-dihydro-3//-pyrimidin-4-ones. The formal 4 - - 2-cycloaddition reaction of ketenimines has been used to synthesize benzoimidazo[l,2-Z ]isoquinolines. ... 

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