Morita Bronsted acids

Asymmetric organocatalytic Morita-Baylis-Hillman reactions offer synthetically viable alternatives to metal-complex-mediated reactions. The reaction is best mediated with a combination of nucleophilic tertiary amine/phosphine catalysts, and mild Bronsted acid co-catalysts usually, bifunctional chiral catalysts having both nucleophilic Lewis base and Bronsted acid site were seen to be the most efficient. Although many important factors governing the reactions were identified, our present understanding of the basic factors, and the control of reactivity and selectivity remains incomplete. Whilst substrate dependency is still considered to be an important issue, an increasing number of transformations are reaching the standards of current asymmetric reactions. 

Akiyama T, Morita H, Itoh J, Fuchibe K (2005a) Chiral Brpnsted acid catalyzed enantioselective hydrophosphonylation of imines asymmetric synthesis of alpha-amino phosphonates. Qrg Lett 7 2583-2585 Akiyama T, Saitoh Y, Morita H, Fuchibe K (2005b) Enantioselective Mannich-type reaction catalyzed by a chiral Bronsted acid derived from TADDOL. Adv Synth Catal 347 1523-1526... 

Some of the catalyst systems used in the asymmetric aldol reaction are also effective in related reactions. Thus, bifunctional catalysts and L-prohne-based organocatalysts have been used to good effect in the nitroaldol reaction and Mannich reaction. The latter process is also effectively catalysed by enantiomeri-cally pure Bronsted acids. Furthermore, much recent progress has been made in the development of a catalytic asymmetric Morita-Baylis-Hillman reaction using Lewis/Bronsted acid catalysts and bifunctional catalysts. 

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction. ... 

Organocatalytic asymmetric hydrophosphonylation/Mannich reactions using thiourea, cinchona and Bronsted acid catalysts 12SL1108. Organocatalytic asymmetric transformations of modified Morita—Bayhs— HiUman adducts 12CSR4101. 

Sasai et al developed a bifunctional BINOL-derived organocatalyst (37) and reported an aza Morita-Baylis-Hillman reaction (Scheme 2.80) [148]. While the 3-pyridyl moiety functioned as a Lewis basic site, the diol moiety worked as a Bronsted acidic site. It is noted that introduction of N-isopropyl-N-3-pyridinylaminomethyl moiety at the 3-position is essential for attaining excellent enantioselectivity. They subsequently introduced 2-diphenylphosphinophenyl group onto the third position and successfully utilized it in the aza Morita-Baylis-Hillman reaction [149]. 

Scheme 7.43 Bronsted acid catalysis of 24 for the Morita-Baylis-Hillman reaction.

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