Formal -cycloaddition

The dihydropyrones are not produced directly in the initial BINOL-titanium(IV)-cat-alyzed reaction. The major product at this stage is the Mukaiyama aldol product which is subsequently cyclized by treatment with TFA [19fj. The formal cycloaddition product 3d (97% ee) obtained from a-(benzyloxy)acetaldehyde is an important intermediate for compactin and mevinolin. Scheme 4.13 outlines how the structural subunit 13 is available in three steps via this cycloaddition approach [19 fj. 

As in CHEC-II(1996), the material gathered in this section concerns all reactions that are formally cycloadditions to the oxadiazole ring (or to the ring and a side chain), including those, which may be stepwise but where no evidence for the mechanism has been provided. 

In the first structurally characterized complexes of type A the metal-phosphorus triple bonds are kinetically stabilized by bulky substituents at the amido ligands. Therefore, these compounds reveal exclusively end-on reactivity via the phosphorus lone pair. This reactivity pattern seems also valid for the solution stable alkoxide derivative [(C/0)3Mo=P], for which the reaction potential is under investigation [13]. In contrast, due to their lesser degree of kinetic stabilization by bulky substituents the short-lived alkoxide containing complexes [(R 0)3W=Pj (R =t-Bu (3c), Ph (3d)), generated by the metathesis reaction between the alkoxide-dimer and the phosphaalkyne (cf. Eq. 8), show additionally a high side-on reactivity towards the phos-phaalkynes of the reaction mixture. Thus, there occurs a formal cycloaddition reaction with the phosphaalkynes, and a subsequent 1,3-OR shift yields the formation of four-membered diphospha-metallo-cyclobutane derivatives 6(Eq. 8) [15,31, 37]. 

Some selected reactions of 21b were investigated [32]. In the reaction with [(Ph 0)4W=0j the dinuclear compound 24 is formed (Eq. 16) containing an almost planar W2OP four-membered ring system. The structure of 24 reveals that after the formal cycloaddition reaction a reductive W-W bond formation occurs under loss of OPh moieties. 

The trienes were then subjected to a formal Diels-Alder reaction using conditions developed by Gilbertson and others (Scheme 8.7) [34]. The propargyl tosylamide 40 and the propargyl ether 43 have both afforded the formal intramolecular Diels-Alder adducts 44 and 45 in high yield. To date, the formal cycloaddition of the siHcon-teth-ered alkyne 41 has not been affected and heating triene 42 led to a thermal Diels-Alder reaction to furnish cycloadduct 46, albeit in lower yield than the corresponding rhodium-catalyzed examples. 

Also in 2009, an elegant combination of two original van Leusen reactions was reported, leading to a MCR toward 4,5-disubstituted oxazoles (19) [136]. The MCR involves the base-induced mono-alkylation of TosMIC (8a) followed by the formal cycloaddition with an aldehyde (Fig. 9). Although dialkylation is a problem often... 

Photochemical reaction with disiliranes leads to a [3-i-2]-cycloaddition (Section 4.3.9). Disilylcyclobutanes [67, 68] and cyclotetrasilanes [68, 69] react in a similar fashion. In both cases the four-membered ring is photolytically cleaved and a diradical is formed. This diradical adds in a formal cycloaddition to the [6,6] double bond of CgQ. The cycloadduct 20 (R = 4-MeCgH4) can be obtained from 19 in 13% yield, but it is not the major product (Scheme 6.12). Rearrangement of an H atom leads to 21 in 46% yield. The product distribution depends strongly on R. Changing R from 4-MeCgH4 to phenyl leads to an exclusive formation of 21. 

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]. 

Collapse of the radical ion pairs can give rise to formal cycloaddition products (206) and dienes can also participate (207). 

Despite the obvious synthetic potential of this formal cycloaddition or annulation reaction, its application has remained little known because of the competing reaction pathways due to 1,2- versus 1,4-addition as well as C-addition versus O-addition [Scheme 4], Moreno-Manas reported a... 

The usage of a,P-unsaturated iminium salts clearly represents a general and efficient solution leading to 2//-pyranyl products exclusively via the C-1,2-addition pathway. The reaction of the pyrone 22 led to the pyran product 23 in a much-improved yield relative to Moreno-Manas s study, and also gave previously unknown products 30b and 30c under these reaction conditions [Scheme 5]. The significance of using preformed a,P-unsaturated iminium salts to control regioselectivity of this formal cycloaddition reaction was recently validated in an account reported by Cravotto.39... 

Reversibility of 67t-Electron Electrocyclic Ring-Closure. The high diastereoselectivity obtained in these reactions here is likely a result of the reversible 67t-electron electrocyclic ring-closure.20,37 41 The best evidence for the reversibility of this ring-closure is described in Scheme 12. We were able to isolate both the desired major isomer 10 and the minor isomer 44 from the formal cycloaddition reaction of the iminium salt 56 with pyrone 12. 

For recent reviews on step-wise [3 + 3] formal cycloadditions leading to bridged carbocycles, pyridines or pyridones using enamines, enaminones, enol ethers, or (J-... 

J. Marco-Contelles, Synthesis of polycyclic molecules via cascade radical carbocycliza-tions of dienynes the first SnPh3 radical-mediated (2 + 2 + 2] formal cycloaddition of dodeca-l,6-dien-ll-ynes, Chem. Commun. (Cambridge), (1996)2629-2630. 

The synthesis of carbacephems 183 and 186 involving C(4)-N(5) bond formation has been described. Carbacephem 183 has been prepared through aza-Achmatowicz rearrangement of 4-(2-furyl) azetidinones (Scheme 32) <1996CC881, 1998SL105>. Azetidinone 175 was obtained by the formal cycloaddition of suitable ketenes with iV-/>-anisyl-2-furylimines. 

An interesting Darzens-like formal cycloaddition of azirines has also been reported <2004EJ02421>. While this is not a true cycloaddition reaction, two bonds are formed in the same reaction sequence. Reaction of sulfone 114 with lithium diisopropylamide (LDA) generates a carbanion which then adds to the azirine to generate intermediate 115. Cyclization of this intermediate with the allyl halide provides the product aziridine 116. This reaction proceeds in only 13% yield but is nonetheless an interesting route to fused-ring aziridines (Equation 27). 

Another type of oxidative (formal) cycloaddition is exemplified by the oxidation of 1,3-diketones in MeCN in the presence of an olefin to di- or tetrahydrofuran derivatives [136] similar products may be obtained by reduction of 2,2-dibromo-1,3-diketones in the presence of an alkene [136]. 

Indole formation from formal cycloaddition of enemine with dibromobenzene. 

Most common are carbene additions, [2 -1- 2]-cycloadditions, [2 -1- 3] heterodipolar cycoladditions [238], and [2 -1- 4]-cycloadditions that comprise Diels-Alder and hetero-Diels-Alder (HDA) reactions [239]. Apart from these, there are also a number of tandem cyclization or condensation reactions that are formal cycloadditions. 

The highly substituted 6-aryl-2-pyrones 28 react with acetophenones 29 in a stepwise base-induced formal cycloaddition reaction. The reaction proceeds via a sequential Michael and aldol reaction in the presence of an alkali metal hydroxide. In this case, the formal cycloadduct 31 extrudes CO2, providing the diene 32, which subsequently undergoes dehydration to afford aromatic products 33 (Scheme 9) <03TL3363>. 

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