Michael additions Brpnsted acid

In 2006, Xu and Xia et al. revealed the catalytic activity of commercially available D-camphorsulfonic acid (CS A) in the enantioselective Michael-type Friedel-Crafts addition of indoles 29 to chalcones 180 attaining moderate enantiomeric excess (75-96%, 0-37% ee) for the corresponding p-indolyl ketones 181 (Scheme 76) [95], This constitutes the first report on the stereoselectivity of o-CSA-mediated transformations. In the course of their studies, the authors discovered a synergistic effect between the ionic liquid BmimBr (l-butyl-3-methyl-l/f-imidazohum bromide) and d-CSA. For a range of indoles 29 and chalcone derivatives 180, the preformed BmimBr-CSA complex (24 mol%) gave improved asymmetric induction compared to d-CSA (5 mol%) alone, along with similar or slightly better yields of P-indolyl ketones 181 (74-96%, 13-58% ee). The authors attribute the beneficial effect of the BmimBr-D-CSA combination to the catalytic Lewis acid activation of Brpnsted acids (LBA). Notably, the direct addition of BmimBr to the reaction mixture of indole, chalcone, d-CSA in acetonitrile did not influence the catalytic efficiency. 

Reactive three-carbon building blocks such as alkynones [32] and 1,3-diaryl pro-penones (chalcones) (for a review on the chemistry of 1,3-diaryl propenones, see e.g. [33]) which can react with bifunctional nucleophiles in a sequence of Michael addition and cyclocondensation open a facile access to five-, six-, and seven-membered heterocycles (Scheme 1). As a consequence, this general strategy has found broad application. However, standard syntheses of alkynones [34] and chalcones [33] are often harsh and require either strongly basic or strongly Lewis or Brpnsted acidic conditions. Therefore, the application in one-pot methodology, where delicately balanced reaction conditions are a prerequisite, is largely excluded. 

It is also worthy to mention that aniline derivatives have been used as nucleophiles in the Michael addition to chalcones [351] and nitrooleflns [352]. Especially interesting has resulted the addition to nitrooleflns, reaction which is catalyzed by the heterochiral [7.7]-P-spirocyclic arylaminophosphonium barfate 196, a novel charged cationic Brpnsted acid catalyst which efflciently promotes the addition of electron-rich anilines to nitrostyrenes and P-alkyl substituted nitrooleflns in toluene at -15°C under very low loading conditions (Scheme 2.124). 

During the last years, organocatalytic asymmetric aza-Michael additions have been thoroughly investigated [62, 63] employing different types of organocatalysis (amine, Brpnsted base, Brpnsted acid, PTC, and enzymatic catalysis). 

Shortly afterward, the same group expanded the scope of Brpnsted acid-catalyzed asymmetric intramolecular aza-Michael addition to activated a,(3-unsaturated... 

As anticipated by the work of Wynberg [7], the presence of a protic group in the catalyst s structure, capable of activating and orienting the electrophile, had a positive impact on the enantioselectivity of the conjugate additions. On this basis, several Brpnsted acid/Brpnsted basic bifunctional catalysts has been applied in the sulfa-Michael addition. A list of them is reported in Figure 14.4. 

When heteronucleophiles react with nitroolefins possessing extended conjuga-ticMi at the p-position, the heteroatoms are appended to a stereogenic allylic or propargylic carlxMi, providing synthetically valuable nitro compounds. For example, aza-Michael addition to nitroenynes under catalysis of the ionic Brpnsted acid, chiral tetraarylaminophosphonium barfate 11, produced the propargylic amine... 

Asymmetric Michael addition of a-cyanoacetates to enones, constructing densely adjacent quaternary and tertiary stereocentres, has been attained by combination of a catalytic action of soft Pd complexes as soft Lewis acids and Brpnsted acids, for example, AcOH. Investigation of the kinetics revealed that the C-C-bond-forming step takes place almost instantaneously with the bis-palladium complex right after the substrate coordination. ... 

Ramachary and coworkers developed an efficient domino reaction between alkyl cyclopentanone-2-carboxylates (109) and 2-(2-nitrovinyl)phenols (78) [61]. The reaction involved a quinine-NH-thiourea (XXX)-catalyzed Michael addition followed by a Brpnsted acid-promoted lactonization, which afforded the spirohydro-coumarins 110 in good to excellent yields (60-90%) and excellent stereoselectivities (up to >99% de up to >99% ee), as shown in Scheme 10.40. 

In 2009, Cai et al. reported a cascade olefin cross-metathesis/intramolecular Friedel-Crafts alkylation for the construction of polycyclic indoles 133 (Scheme 5.89) [90], A Ru complex (134)/chiral Brpnsted acid [(S)-135] binary system was used in this relay catalysis. Recently, the same group reported an enantioselective intramolecular aza-Michael addition of indoles using a similar binary catalyst system (Scheme 5.90) [91]. 

In 2009, Wang et al. reported a tandem reaction with the combination of phase-transfer and Brpnsted acid catalysis for the asymmetric synthesis of chiral N-heterocycles [37]. The one-pot tandem reaction was initiated by Michael addition... 

Beyond secondary amines, various chiral Brpnsted acid and hydrogen-bonding donor catalysts, supported primary amines were also demonstrated to be suitable catalysts to implement metal/organic binary catalytic systems. In 2006, McQuade et al. reported a cascade three-component reaction by combining encapsulated amine and nickel catalysts with high reactivity and chemoselectivity [81]. The reaction proceeded through an encapsulated amine-promoted nitroalkene formation via iminium ion intermediate followed by a nickel complex-promoted chemoselective Michael addition of dimethyl malonate to the newly generated nitroalkene (Scheme 9.76). 

Wabnitz TC, Spencer JB. A general, Brpnsted acid-catalyzed hetero-Michael addition of nitrogen, oxygen, and sulfur nucleophiles. Org. Lett. 2003 5 2141-2144. 

Olefin cross-metathesis followed by intramolecular oxa-Michael addition, catalysed by the second-generation Hoveyda-Gmbbs catalyst, has been developed as a cascade, one-pot procedure for 5-hydroxy olefins (147) and a,/ -unsaturated carbonyl compounds (148) (trani-crotonaldehyde or A-acryloyl-2,5-dimethylpyrrole, etc.) as the reacting partners. In the presence of a Brpnsted acid in CH2CI2 at 25-35 °C, the resulting 2,6-cA-substituted tetrahydropyrans (149) were obtained with excellent diastereoselectivity. The role of ruthenium hydride intermediates has been investigated in detail. 

A one-pot Michael and aza-Michael addition with concomitant ring closure has been achieved on addition of tryptamine (309) to 2 equiv of enones in the presence of the axially chiral phosphoric acid (18) as a Brpnsted catalyst. The resulting adducts (310) were obtained with <83%... 

The modified prolinol derivative (324) has been developed as a readily recyclable catalyst for the Michael addition of malonates CH2E2 (E = C02RO to enals RCH=CHCH=0, which proceeds at 10mol% loading in the presence of PhC02H (40%) as the Brpnsted acid cocatalysts in a mixture of H2O and Pr OH (3 2). The Michael adducts RCH(CHE2)CHCH=0 were thus obtained in <97% ee ... 

Chen et al. [26] reported the use of a bifunctional thiourea catalyst 61 during the organocatalyzed thia-Michael addition of thiophenol to unsaturated imide 58c (Scheme 3.29). Michael adduct 60c was obtained in 60% ee and 97% yield by conducting the reaction in dichloromethane at -78°C. The authors speculated that while the tertiary amine of the bifunctional catalyst 61 would act as a proton shuttle according to a Brpnsted acid/base catalysis, the presence of the thiourea moiety might possibly cooperate in the stabilization of the more stable Z-enolate intermediate via hydrogen bond formation as illustrated in Scheme 3.31. 

Other nucleophiles such as nitromethane can also be used for this reaction. Thus, by the catalysis of (fl)-LPB (LaK3tris((/ )-binaphthoxide) (20 mol %), in which La works as a Lewis acid and K-naphthoxide works as a Brpnsted base, nitromethane reacted with chalcone to give the Michael adduct in 85% yield and 93% ee (Scheme 8D.8) [22], Addition of BuOH (120 mol %) gave a beneficial effect on the reactivity as well as the enantioselectivity of this reaction. 

In 2008, Michael and coworkers [61] reported an intramolecular oxyaminatitHi of urea derivatives 74 having pendant unactivated alkenes using PhIO as an oxidant and Brpnsted or Lewis acid as a promoter to furnish bicycUc isoureas 75 via syn addition (Scheme 18 (l)).Farid et al. [62] recently disclosed the asymmetric version of such a transformation. The authors described an efficient chiral hypervalent iodine 78-mediated oxidative cyclization of alkenyl ureas 76 to optically pure isourea derivatives 77 (Scheme 18 (2)). 

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