Reactions Rauhut-Currier

Also known as Morita-Baylis-Hillman reaction, and occasionally known as Rauhut-Currier reaction. It is a carbon—carbon bond-forming transformation of an electron-poor alkene with a carbon electrophile. Electron-poor alkenes include acrylic esters, acrylonitriles, vinyl ketones, vinyl sulfones, and acroleins. On the other hand, carbon electrophiles may be aldehydes, a-alkoxycarbonyl ketones, aldimines, and Michael acceptors. 

The Rauhut-Currier Reaction is a similar reaction involving two enone coupling partners ... 

Other references related to the Rauhut-Currier reaction are cited in the literature. ... 

Scheme 2.25 Enantioselective intramolecular Rauhut-Currier reaction catalyzed by 31a.

In a completely different context, an A-protected version of the amino acid cysteine has been found to be an excellent promoter for the intramolecular Rauhut-Currier reaction (Scheme 6.20)," in which an enolizable enone played the role of the Michael acceptor, adding to another a,p-unsaturated ketone moiety in already present at the substrate structure. The mechanism of the reaction involved the activation of the enone which has to play the role of the donor by the catalyst via sulfa-Michael addition through the mercapto functionality of the A-protected cysteine derivative. The formed enolate... 

The Morita-Baylis-Hillman reaction is, in general, a carbon-carbon bondforming reaction of an a,(3-unsaturated compound with an aldehyde mediated by an organic nucleophilic base resulting in the formation of an allylic alcohol. Morita reported the use of a phosphine as catalyst and Baylis and Hillman used a tertiary amine. Variation of the electrophile to electron-deficient alkenes in a Michael-Michael elimination sequence leads to homo- and heterodimerisation and is known as the Rauhut-Currier reaction. The electrophilic aldehyde could be substituted by an imine or derivative in the aza-Morita-Baylis-Hillman reaction. Recently, there has been an increase in the use of this reaction for the construction of many different targets using many different amine derived catalysts. Scheme 2.2 shows a general view of this reaction and the accepted mechanism. ... 

In this chapter, asymmetric organocatalyzed umpolung conjugate additions are considered. Particular emphasis on deconjugative Michael additions with a,a-dicyanoalkenes, the intramolecular Rauhut-Currier reaction, and the Stetter reaction is placed. These are very efficient transformations in the synthetic chemist s arsenal, but they are also challenging to control. 

The intramolecular enantioselective Rauhut-Currier reaction [295] generates optically active cycloalkenes from acyclic precursors bearing two tethered Michael acceptors. In 2(X)7, Miller et al. reported the first organocatalyzed intramolecular cyclization of symmetrical bis(a,P-unsaturated ketones) to afford in good yields... 

Scheme 2.107 Enantioselective organocatalyzed Rauhut-Currier reaction of bis(enones)...

The MBH reaction of acrylates CH2=CHC02R with isatins, employing the bifunctional phosphinothiourea catalysts (198), afforded the corresponding 3-hydroxy-2-oxindole derivatives with moderate enantioselectivity (<69% ee). orf/io-Mercaptobenzoic acid and ort/io-mercaptophenols 2-X-QH4SH (X = CO2H or OH) have been shown to act as multifunctional Lewis basic catalysts for both the intramolecular MBH and Rauhut-Currier reaction in aqueous solutions. The catalytic activity of these protic nucleophiles is believed to originate from a Brpnsted acid-induced destabilization of the intermediate thioethers. ... 

The stereoselective Rauhut-Currier reaction catalysed by a cysteine derivative has been explored computationally with DFT (M06-2X). Both methanethiol and a chiral cysteine derivative have been studied as nucleophiles. The complete reaction pathway involves rate-determining elimination of the thiol catalyst from the Michael addition product and the stereochemistry has been found experimentally to be extremely sensitive to the reaction conditions, such as the number of water equivalents and the effect of potassium counterion. 

In addition, a C6 thiourea derivative of P-isocupreidine 25 has been prepared and shown to catalyze the Rauhut-Currier reaction between allenoates and maleimides with the formation of products in a high yield but only moderate ee (Scheme 6.30) [72]. 

More recently. Miller and coworkers reported that ortho-mercaptobenzoic acid and ortho-mercaptophenols 159 could be used as efficient thiol catalysts in both the intramolecular MBH and Rauhut-Currier reaction and they also demonstrated that chiral mercaptophenol afforded the reaction with low to moderate enantiose-lectivities (Scheme 31.53) [64]. Under estabhshed conditions, chiral catalysts (S)-and (R)-160 afforded high yields and moderate asymmetric inductions in the MBH reactions. The obtained enantioselectivities remained largely unaffected by the amount of water and base added, catalyst loading, and substrate concentration but were markedly influenced by the reaction temperature. Interestingly, both increasing and decreasing the temperature from the established value of 70 °C resulted in lower ee values. The complete absence of catalytic activity of (R)-161 further emphasizes the crucial importance of a protic substituent at the ortho-position to the nucleophilic thiol. 

Miller disclosed the first enantioselective intramolecular Rauhut-Currier reaction (also called vinylogous MBH reaction). A stoichiometric amount of protected cysteine derivative 84 and potassium tert-butoxide (1.5 eq.) were employed, and various bis-enones 85 were converted into cyclohexene products 86 in good yields and with high enantioselectivity (Scheme 36.22). Using a lower loading of 84 leads to a reduced yield but nearly identical ee [28a]. 

The prochiral MBH substrates (360) have been converted into a-alkylidene-y-butyrolactones (361) with <98% ee via the intramolecular Rauhut-Currier reaction, catalysed by the L-valine-derived tosylamido phosphine (362). ... 

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