Cycloadditions also

The 27T-electrons of the carbon-nitrogen double bond of 1-azirines can participate in thermal symmetry-allowed [4 + 2] cycloadditions with a variety of substrates such as cyclo-pentadienones, isobenzofurans, triazines and tetrazines 71AHC(13)45). Cycloadditions also occur with heterocumulenes such as ketenes, ketenimines, isocyanates and carbon disulfide. It is also possible for the 27r-electrons of 1-azirines to participate in ene reactions 73HCA1351). 

For the synthesis of estradiol methyl ether 4-319, the cydobutene derivative 4-317 was heated to give the orthoquinonedimethane 4-318 which cydized in an intramolecular Diels-Alder reaction [109]. The thermally permitted, conrotatory elec-trocyclic ring-opening of benzocyclobutenes [110] with subsequent intramolecular cycloaddition also allowed the formation of numerous complex frameworks (Scheme 4.70). 

An intramolecular cycloaddition also occurred with 3-ylidenepiperazine-2,5-diones such as 124 or 125, obtained by Wittig-Horner-Emmons reaction from phosphonate 121 and aldehydes 122 or 123, respectively. The products of the Diels-Alder reaction are the bridged bicyclo[2.2.2]diazaoctane rings 126 and 127 that have been found in biologically active secondary metabolite such as VM55599 and brevianamide A. The different type of structures employed in this case requires a chemoselective reaction in order to produce the expected products as single diastereoisomers after 20 days (Scheme 18) <2001JOC3984>. 

Such 2 + 2 cycloadditions also confirm the generality of Woodward-Hoffinann rule. 

Elliott et al. [155] proposed a concerted cycloaddition also for the reaction of 417 with 1,1-dimethylallene to yield 426. However, even the 1,2-bismethylenecyclobu-tane entity of 426 provides support for a diradical intermediate, since it is characteristic of the dimers of many allenes (see, for example, Schemes 6.10 and 6.25). It is generally accepted that these [2+ 2]-cycloadditions proceed via diradicals as intermediates. 

Like the nitrone-olefin [3 + 2]-cycloaddition, the nitrone-allene [3 + 21-cycloaddition also takes place regioselectively to furnish methylene-substituted isoxazoli-dine derivatives. The substituents of the 3- and 4-positions of the cycloadducts 72a and 72b are disposed cis in contrast, the reaction of 70 with allenyl sulfone 71c gives rise to the trans-cycloadduct 72c exclusively (Table 12.4). On treatment with base or heating, methyleneisoxazolidines 72 readily rearrange to isoxazo-lines via a 1,3-hydrogen shift. 

This section shall consider the effects of substitution on both the nitronate as well as the dipolarophile, as they relate to both the inter- and intramolecular versions of the dipolar cycloaddition. Also included will be a discussion of facial selectivity in the reaction of a chiral dipolarophile. 

Harwood and co-workers (105) utihzed a phenyloxazine-3-one as a chiral derived template for cycloaddition (Scheme 4.50). An oxazinone template can be formed from phenylglycinol as the template precursor. The diazoamide needed for cycloaddition was generated by addition of diazomalonyl chloride, trimethyl-dioxane-4-one, or succinimidyl diazoacetate, providing the ester, acetyl, or hydrogen R group of the diazoamide 198. After addition of rhodium acetate, A-methylmaleimide was used as the dipolarophile to provide a product that predominantly adds from the less hindered a-face of the template in an endo fashion. The cycloaddition also provided some of the adduct that approaches from the p-face as well. p-Face addition also occurred with complete exo-selectivity. Mono- and disubstituted acetylenic compounds were added as well, providing similar cycloadducts. 

An intramolecular nitrile oxide cycloaddition also served as the key step in the stereoselective assemblage of the skeleton of angular triquinane sesquiterpenes of the isocomene series. Tetracyclic isoxazoline 203 was obtained from oxime 202 [derived from tetrahydroindandione 201] and on treatment with sodium hypochlorite... 

Intramolecular nitrile oxide-alkene cycloadditions also provide efficient access to six-membered rings such as cyclohexanes or decalins that are heavily adorned with functional groups and side chains. For example, this strategy was used to prepare racemic hemaldulcin (213), which is a 3,6-disubstituted cyclohexenone found in a Mexican plant that possesses a strong sweet taste. Starting from (2Z,6E)-famesal (209) (328) (Scheme 6.88), the aldehyde was treated with hydroxylamine... 

Thus, (2R)-pumiliotoxin C (214) has been prepared from (R)-norvaline (212). The asymmetric center in the triene (213) controls the configuration at three carbon atoms 210). a-Kainic acid, isolated from the algae Digena simplex and Centrocerus clavulatum, was prepared by total synthesis. Its enantioselective synthesis involved a stereocon trolled intramolecular cycloaddition of a (S)-glutamic acid211). Asymmetric cycloadditions also play a decisive role in the synthesis of chiral cytochalasins. In this case 212> the primary chiral information was carried by (S)-alanine and (S)-phenylalanine, respectively. 

We focused on 3-cyanochromone derivatives, for the dienophilic reactivity of these compounds has gone unnoticed.18 In addition, these 3-cyanochromones could serve as excellent model systems for exploring the potential of our strategy and investigating the scope [i.e. regio- and stereoselectivity] of y-pyrones in [4 + 2] cycloadditions. As a result, this cycloaddition also became a subject of research by other groups.19... 

Intermolecular cycloaddition also proceeds smoothly. The 2,8-dioxabicyclo-[3,2.1]octane core system 379 of zaragozic acid 380 was constructed by the intramolecular carbonyl ylide formation from 376 catalysed by Rh2(OAc)4, followed by intermolecular 1,3-dipolar cycloaddition of the electron-deficient dipolarophile 377 as shown by 378 as a single diastereomer out of four possible diastereomers [124],... 

The dihydrothiopyran unit has been fused onto [60]fullerene through reaction with a thioacrylamide and an acyl chloride (95CC565). Cycloadditions also feature in the synthesis of... 

Especially fast 1,3-dipolar cycloadditions also can be expected whenever the denominator... 

Especially fast 1,3-dipolar cycloadditions also can be expected whenever the denominator of the second term is very small, so that the magnitude of the second term is high. This scenario characterizes the so-called Sustmann type III additions. Therein, it is essentially the HOMOdip0iar0phiie/LUMOdip0le interaction which stabilizes the transition state (Figure 12.35, column 4). 

Other types of tungsten-alkene complexes that merit mention include the first group six jj -benzene complex, TpW(NO)(PMe3) ((( -CeHe), that contains a tt-bound benzene ligand activated toward Diels-Alder cycloaddition.Also, the jj -fiillerene complexes, mgr-W(CO)3(L-L)(jj -C6o) (65), have been prepared from W(CO)4(L-L) (L-L = a bidentate N- or P-donor ligand) in the presence of In some... 

Intramolecular [2 + 2] cycloaddition also occupies a pivotal position among the methods available for the synthesis of highly strained compounds. Owing to the proximity effect, this reaction occurs easily even in sterically encumbered cases. The synthesis of one of the first representatives of exotic hydrocarbons, Dewar benzene 388 by van Tamelen, was achieved by a surprisingly short route (Scheme 2.130). The readily available Diels-Alder adduct 389 was first converted into diene 389a. The latter underwent intramolecular [2 -i- 2] cycloaddition which led to the formation of the [2.2.0] bicyclohexene framework of the key intermediate 390. 

Diels-Alder Reactions. Chiral a,p-unsaturated imides participate in Lewis acid-promoted Diels-Alder cycloaddition reactions to afford products in uniformly excellent endo/exo and endo diastereoselectivities (eq 50 and 51). Unfortunately, this reaction does not extend to certain dienophiles, including methacryloyl imides, p,3-dimethylacryloyl imides, or alkynic imides. Cycloadditions also occur with less reactive acyclic dienes with high diastereoselectivity (eq 52). Of the auxiliaries surveyed, the phenylalanine-derived oxazolidinones provided the highest diastereoselectivities. This methodology has been recently extended to complex intramolecular processes (eq 53). In this case, use of the unsubstituted achiral oxazolidinone favored the undesired diastereomer. 

Both Diels-Alder and hetero-Diels-Alder reactions can be rendered stereoselective using l copper(II) salts, but inferior levels of stereoselection were observed relative to other pybox derivatives. Lanthanide-catalyzed 1,3-dipolar cycloaddition also exhibited moderate (61%) enantioselection. ... 

Silyl enolates of a,a-dialkoxy ketones react with furans to form [3 4- 4] cycloaddition products in the presence of SbCls (Eq. 6) [17], Cycloaddition also occurs when 2,2-dialkoxycyclopropanecarboxylic esters and carbonyl compounds are treated with SbCls [18]. 

---