Formal Cycloaddition Reactions

The Saigo group disclosed the first highly enantioselective self-annulation of enals catalyzed by the cyclophane-type chiral NHC to afford y-butyro-lactones (91-99% ee for the trans isomers). a,a,a-Trifluoroacetophenone 

Cheong, Schiedt, and their co-workers have developed a highly efficient synthesis of enantioenriched y-butyrolactones by NHC-catalyzed annula-tion of enals and a-keto phosphonates (up to 93% yield, 2.9 1 dr, 91% ee). Enhanced levels of enantioselectivity were achieved through a rational 

The Scheidt group reported a highly enantioselective NHC-catalyzed addition of a,p-unsaturated aldehydes to isatins activated by lithium cations (up to 93% yield, 20 1 dr, 97% ee). The addition of lithium chloride as a Lewis acid with p-aryl substituted enals generates lactone products with high enantioselectivity (up to 93% ee) which result from an organized transition 

Seheme 7.38 NHC-catalyzed as)mimetric cross-annulation of aromatic enals and isatins reported by Ye. 

In 2013, the She group reported an efficient NHC-catalyzed addition of alkynyl aldehydes to P,y-unsaturated a-keto esters to generate butenolides 

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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 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. 

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>. 

Formal Cycloaddition Reactions 15.2.5.1. Diels-Alder reactions of silyloxydienes... 

Several examples of the formal cycloaddition reaction mediated effectively by KHMDS were described (eq 91). 

Synthesis of Aromatic Compounds. (Formal) Cycloaddition Reactions... 

Synthesis of saturated heterocycles via metal-catalyzed formal cycloaddition reactions that generate a C—N or C—O bond 13THC(32)225. Synthesis of saturated heterocycles via metal-catalyzed alkene carboami-nation, carboalkoxylation diamination, aminoalkoxylation, dialkoxyla-tion hydroamination or hydroalkoxylation reactions 13THC(32)1, 13THC(32)39, 13THC(32)109. 

The gold-catalyzed formal cycloaddition reactions of 2-ethynylbenzyl ethers with 8-methylquinoline oxide and ethyl diazoacetate led to a skeletal rearrangement of the benzo[c]furan motif through an attack of the diazo compound on the initial oxonium species in the alkyne activation route, followed by a Roskamp-type rearrangement and ring closure (13AGE7559). 

Transition metal catalysts can exert an important influence on the regio-selectivity of formal cycloaddition reactions. Cycloaddition of butadiene and XLIV in the absence of metal catalysts takes place at 135° giving a 20 1 mixture of XLV and XLVI. Catalysis by the Ni(acac)2-triphenylphosphine-triethylaluminum system affords XLVI, XLVII as the major product, and only a trace of XLV (Garratt and Wyatt, 1974). A bis(7r-allyl)nickel(0) complex (XLVIII) has been suggested as a reaction intermediate. 

It is widely appreciated that the 1,3-cycloaddition is a pericyclic reaction, which proceeds through a concerted mechanism. However, many other cycloaddition reactions do not perform via a concerted manner, which could be called formal cycloaddition reactions. Studer and coworkers reported the first examples of highly enantioselective formal [3-1-2] cycloadditions of allyltin derivatives 48 with 2-nitrosopyridine 49 to give substituted isoxazolidines 50 [26]. It was found that the use of [Cu(MeCN)4]PF6 and Walphos-CFj ligand 51 was essential for obtaining high yield and enantioselectivity (Scheme 2.14). 

I 2 TMS-Prolinol Catalyst in Organocatalysis Formal cycloaddition reactions (as "diene") ... 

Building on the shoulders of these predecessors, we continued our own efforts and developed a more general solution to render acyclic enals useful in this formal cycloaddition reaction. To solve the competing reaction pathway problem or to improve the pathway leading to the desired... 

The control of regioselectivity by using preformed a,(3-unsaturated iminium salts in this formal cycloaddition reaction was recently validated in an account by Cravotto et al. (Scheme 12.7) [26]. Reactions of 4-hydroxycoumarin 43 with a series of a,(3-unsaturated iminium salts, pregenerated from their respective enals under conditions similar to those we have reported, led to pyranocoumarins such as 45a-45d all in good yields with notably (3-unsubstituted enal also being suitable (see 45a). No stereochemical information was provided for 45c and 45d but they appeared to be single isomers. 

The chemistry of copper carbenoids involved in the catalytic decomposition of diazo compounds and related tosylhydrazones has been reviewed. Many aspects of these catalytic transformations are covered including not only the classical cyclopropanation and X-H insertion processes but also a range of formal cycloaddition reactions, the reactions involving ylide formation, and the various coupling reactions of diazo derivatives. An account more focused on asymmetric metal-catalysed X-H insertion has been published. Through this review, the dependence on the nature of the metal and its i ligands can be evaluated for these 0-H, N-H, S-H, and Si-H insertions of carbenoids. 

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