Organocatalytic olefins

As a third example for an organocatalytic reaction, based on multiple hydrogen bonding and mechanistically investigated by DFT, we selected olefin epoxidation with hydrogen peroxide in fluorinated alcohol solvents, such as 1,1,1,3,3,3-hex-afluoro-2-propanol (HFIP) (Scheme 8). Here we encounter a new type of catalytic hydrogen bond the cooperative hydrogen bond. 

In this section, we review the development of organocatalytic ylide-based epox-idation methods which allow a one-step route from carbonyl compounds, and therefore compete with the more traditional two-step approach of olefination followed by epoxidation of the resulting alkene (see Scheme 10.1) [13]. Indeed, ylide-based methodologies side-step the construction of a C=C double bond and achieve the whole transformation in one step thus, they are potentially more atom-efficient (see Scheme 10.1). However, there are greater challenges as both the absolute and relative stereochemistries must be controlled in one step [14-22]. 

Organocatalytic Enantioselective Reduction of Olefins, Ketones, and I mines... 

Asymmetric Organocatalytic Reduction of Olefins 395 Table 11.1 Organocatalytic reduction of conjugated aldehydes by Hantzsch ester 4 [14]. 

Shi Y (2004) Organocatalytic asymmetric epoxidation of olefins by chiral ketones. Acc Chem Res 32 488... 

Organocatalytic asymmetric epoxidation of olefins by chiral ketones 04ACR488. 

Organocatalytic Asymmetric Epoxidation of Olefins by Chiral Ketones ... 

Several organocatalytic variants for the conjugate addition of electron-rich aromatic substrates to electron-deficient olefins have been reported in the last few years which apply the concept of activation of the electrophile by hydrogen-bonding interactions. In this context, chiral bifunctional thiourea ent-91 has been employed as an excellent promoter for the enantioselective conjugate... 

Rondan, N. G., Paddon-Row, M. N., CarameUa, R, Houk, K. A. (1981). Nonplanar Alkenes and Carbonyls A Molecular Distortion which Parallels Addition Steroselectivity. J. Am. Chem. Soc., 103,2436. Ess, D. H. Houk, K. N. (2007). Distortion/Interaction Energy Control of 1,3-Dipolar Cycloaddition Reactivity. J. Am Chem. Soc., 129, 10646-10647. Lopez, S. A., Houk, K. N. (2013). Alkene Distortion Energies and Torsional Effects Control Reactivities, and Stereoselectivities of Azide Cycloadditions to Norbomene and Substituted Norbomenes. J. Org. Chem., 78(5), 1778-1783. Hong, X., Liang, Y, Griffith, A. K., et al. (2013). Distortion-Accelerated Cycloadditions and Strain-Release-Promoted Cycloreversions in the Organocatalytic Carbonyl-Olefin Metathesis. Chem. Sci., 5(2), 471-475. 

Organocatalytic Oxidation. Asymmetric Epoxidation of Olefins Catalyzed by Chiral Ketones and Iminium Salts Wong, O.A. Shi, Y. Chem. Rev. 2008,108,3958. 

The organocatalytic asymmetric conjugate addition of heteroatom nucleophiles to different electrophilic olefins has become a very popular reaction during the last few years. Different nitrogen, oxygen, sulfur, and selenium nucleophilic species have been successfully used leading to enantiomerically emiched heterofunctionalized derivatives. 

An organocatalytic asymmetric formal [3 + 2] cycloaddition reaction of isocya-noesters 218 to nitroolefins 210 leading to highly optically active dihydropyrroles 220 was reported by Gong, et al., Scheme 3.70 [87], The proposed mechanism is depicted in Scheme 3.70 the cinchona alkaloid chiral base 219 promote an asymmetric Michael addition of isocyanoesters to electron-deficient olefins (nitroolefins), and subsequent intramolecular cyclization of the intermediate to afford the dihydropyrroles 220. 

The nucleophilic 1,4-addition of stabilized carbon nucleophiles to electron-poor olefins, generally a,fS-unsaturated carbonyl compounds, is known as Michael addition, although it was first reported by Komnenos [14] in 1883. Michael-type reactions can be considered as one of the most powerful and reliable tools for the stereo-controlled formation of carbon-carbon and carbon-heteroatom bonds [15], as has been demonstrated by the huge number of examples in which it has been applied as a key strategic transformation in total synthesis. As a consequence, in recent years, many different organocatalytic versions of this important transformation... 

Scheme 19.33 Organocatalytic asymmetric vinylogous Michael (AVM) reaction of 3-alkylidene oxindoles with nitro-olefins promoted by thiourea 17.

In addition to the electron-deficient olefins, alkynones were also suitable electrophiles. In 2004, Jprgensen and Bella [88] developed the first organocatalytic enantioselective conjugated addition of 1,3-dicarbonyl compounds to alkynones utilizing cinchona alkaloids catalyst 85 (Scheme 5.43). Both aromatic and aliphatic... 

The tertiary phosphine catalyzed [3+2] cycloadditions of allenoates 98 and electron-deficient olefins 99 was first discovered by Zhang and Lu [61] in 1995. Only two years later, the first enantioselective organocatalytic version of this reaction was reported by Chen and co-workers [62]. They showed that chiral phosphabicyclo[2.2.1]heptanes 100 catalyzes this reaction to give synthetically interesting optically active cyclopaitene derivatives 102 (Scheme 6.23). The mechanism for this reaction was later investigated... 

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