1,3-Cycloaddition base catalyzed

The Staudinger reaction [92], a [2 + 2]-cycloaddition of a ketene and a nucleophilic imine, usually proceeds by an initial imine attack on the ketene thus forming a zwitterionic enolate which subsequently cyclizes. This reaction is an expedient route to p-lactams, the core of numerous antibiotics (e.g., penicillins) and other biologically active molecules [93]. In contrast, for Lewis-base catalyzed asymmetric reactions, nonnucleophilic imines are required (to suppress a noncatalyzed background reaction), bearing, for example, an N-Ts [94] or -Boc-substituent [95]. 

Dehydrobromination of 219 with DBU gave rise to allyl propargyl ethers 220, which underwent a base-catalyzed isomerization-[4 +2]-cycloaddition sequence to afford tricyclic enol ethers 221 [179]. 

While arylnitrile oxides dimerize in protic solvents and in pure pyridine (cf. 4.04.8.1.3.), they form bis(adducts) (191) and (192) via zwitterions (189) with pyridine in apolar solvents (Scheme 83) <89JHC757,90Gi>. Significantly, the cycloaddition of the nitrile oxide to pyridine to give (190) is not a concerted process. Heterocycles (191) undergo base catalyzed ring cleavage (Scheme 84). 

Mechanisms that are probably associated, respectively, with these processes are (i) the formation of betaine intermediates (306) (Fig. 3) 103,143,149,197,200 homolysis or heterolysis of the X—Z bond (304) or the X—Z bond (305) giving diradicsd (307) or dipolar (308) intermediates, (iv) 1,3-dipolar cycloaddition yielding intermediate adducts (e.g, 309), The base-catalyzed rearrangements (ii) present very interesting mechanistic problems suitable for speculation and experimental enquiry. 

Reactions by Other Nucleophiles As in the case of the formal cycloadditions of alkenes to allyl cations, the addition of alkenes to gold(I)-activated allenes generates intermediates that determine which cycloaduct formed. Based on this hypothesis, Toste et al. recently developed enantiorich bicycle-[3.2.0] structures by [2+2]-cycloaddition reaction catalyzed by chiral biarylphosphinegold(I) complexes [51]. 

The intramolecular cycloaddition of an alkene to a heterocyclic system has been shown to effect vicinal functionalization of the alkene with formation of two new carbon bonds (75CC502). The dioxopyrimidine (760), prepared by base-catalyzed condensation of... 

Diels-Alder cycloadditions of the readily available spiro[2.4]heptadiene (15) are a useful entry to spiro(cyclopropane-l,7 -norbornene) and related polycyclic compounds (equation 17)38. 1,1 -Diacetylcyclopropane was found to undergo unusual base catalyzed cyclizations resulting in spiroannulated cyclopropanes (equation 18)3,-4°. 

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 cycloaddition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-catalyzed 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] cycloadditions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Intramolecular azomethine ylide cycloaddition to the C—O double bond of an aldehyde was reported in 197369 and cycloaddition to the C—C double bond was first reported in 1975.70 Competition between 1,1- and 1,3-cycloaddition is observed in intramolecular reactions, although intermolecular reactions give only 1,3-cycloaddition. Photolysis of 2//-azirines is one generation method of nitrile ylides applicable to intramolecular cycloaddition.70 Another method involves the base-catalyzed 1,3-elimination of hydrogen halide from alkenyl imidoyl halides. Still other procedures involve thermolytic and photolytic cycloreversions of oxazolinones and dihydrooxazaphospholes. 

Intramolecular cycloaddition of azides and nitriles has often been used for the preparation of fused tetrazoles, tetrazoloazines, or similar compounds. In protic solvents, 2-azidobenzaldehyde undergoes base-catalyzed condensation with cyanocarbanions to yield tetrazolo[l,5-tf]quinolines 553 (Scheme 81) <1997S773>. 

The singlet oxygen ( C ) cycloaddition to electron-rich alkenes is by far the most prevalent method used for the construction of 1,2-dioxetanes. The Kopecky method, which relies on the cyclization of a /3-halo hydroperoxide, is rarely utilized these days but was heavily relied upon in the past. The base-catalyzed cyclization of /3-epoxy hydroperoxides also appears to becoming more popular. There are also several miscellaneous methods that have been utilized for specific dioxetane examples and these are summarized in Section 2.16.7.1.3. 

Steroidal, alicyclic or aromatic annulated pyridines were prepared via a microwave-assisted, base-catalyzed Henry reaction of /1-formyl enamides and nitromethane on an alumina support [97]. Highly substituted tri- and tetrasubstituted pyridines were synthesized in a Bohlmann-Rahtz reaction from ethyl /3-amino crotonate and various alkynones. The reaction involved a Michael addition-cyclodehydration sequence and was effected in a single synthetic step under microwave heating conditions [98]. An alternative approach towards polysubstituted pyridines was based on a reaction sequence involving an inverse electron-demand Diels-Alder reaction between various enamines 45 and 1,2,4-triazines 44 (Sect. 3.6), followed by loss of nitrogen and subsequent elimination-aromatization. Enamines 45 were formed in situ from various ketones and piperidine under one-pot microwave dielectric heating conditions [99]. Furthermore, a remarkable acceleration of the reaction speed (from hours and days to minutes) was observed in a microwave-assisted cycloaddition. Unsymmetrically substituted enamines 45 afforded mixtures of regioisomers (Scheme 35). 

Recently, we reported an entirely new and efficient formal [3 + 2] cycloaddition based on the hydrocarbonation reaction of allenes. The palladium-catalyzed reaction of the activated olefins 4 with allenes 26, bearing an acti-... 

Triazolo-diazocine 12 was obtained through a [6+2] cycloaddition of cycloocta-l,3-dione and 4-pyren-l-yl-l,2,4-triazole-3,5-dione 80. Such a triazole derivative was obtained by in situ oxidation of l,2,4-triazolidine-3,5-dione 81, which was in turn obtained by reacting isocyanates and semicarbazides, followed by base-catalyzed cyclization... 

An important feature, characteristic of virtually all fulvene-mediated strategies thus far described in the literature, is the relative ease with which the addends can be assembled from readily available starting nuterials prior to cycloaddition. Customarily, a simple base-catalyzed condensation of an appropriate ketone substrate with a cyclcqientadienide anion will suffice to provide good yields of the requisite ful-... 

Magnus was the first to develop extensive synthetic applications of the Pauson-Khand preparation of the bicyclo[3.3.0]oct-l-en-3-one system. His efforts amply demonstrate the degree to which the high level of functionality in the Pauson-Khand products can be directly utilized in building more complex structures. A formal synthesis of the antitumor sesquiterpene coriolin illustrates a very efficient sequence for construction of the third ring in the linearly fused triquinane series in the presence of considerable functionality (Schemes 10 and 18). A synthesis of the related triquinane hirsutic acid utilizes the observation that the proper stereochemical relationship between the substituents at C-7 and the ring-fusion carbon (C-5) of the bicyclo[3.3.0]oct-l-en-3-one system, while not controllable in the cycloaddition reaction itself, may be readily established by acid- or base-catalyzed equilibration (equation 54 and Scheme 19). ... 

The decomposition of cyclic sulfones and sulfoxides has attracted increasing attention recently in view of their relationship to cyclic fragmentation reactions and of the dramatic impact of the Woodward-Hoffman rules for intermolecular cycloaddition and electrocyclic ring opening reactions. The simplest cyclic sulfone known is 2,3-diphenyl thiirene-1,1-dioxide (A) which was isolated by Carpino and McAdams by the Ramberg-Backlund base catalyzed dehydrohalogenation of a, a -dibromodibenzylsulfone, viz. 

Pyridinium-7V-(irnidoyI)imides 110, prepared from the base-catalyzed reaction of jV-aminopyridinium salts and JV-ethoxycarbonyl imidates, undergo initial intramolecular cycloaddition in refluxing xylene to afford unstable triazoline intermediates 111, which rearomatize to triazoles in a second step (77JOC443). 

Asymmetric Cycloaddition Reactions Catalyzed by Cinchona-Based Primary Amines 313... 

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