Michael reactions guanidine-catalysed

Scheme 4.15 Axial guanidine catalysed aza-Michael reaction...

Asymmetric nitro-Michael reactions of methyl vinyl ketone (MVK) in the presence of bicyclic guanidine with a benzhydryl group led, disappointedly, to low asymmetric induction (9-12%) [21a] Trials for the reaction of 0 ,p-unsaturated y- or 8-lactones with pyrrolidine in the presence of the conjugate acids of a bicyclic guanidine [50] or the Murphy s guanidine [24a] (R = Me in Scheme 4.7) resulted in the production of racemic compounds. The latter phase transfer catalyst (PTC) catalyses the nitro-Michael addition of chalcone but with limited range (70% yield, 23% ee) [24c]. 

Ma et al. examined guanidine catalysed Michael reaction of ferf-butyl glycinate Schiff base with ethyl acrylate in THF and observed 30% ee as the asymmetric induction when an acyclic guanidine (2) was used as a catalyst [10b]. Ishikawa et al. succeeded in greatly improving the asymmetric induction by the use of guanidine 17a, originally prepared based... 

Excellent conversions and selectivities were observed both with respect to the alkene and the primary oxidant [62]. In nitro-Michael reaction it was noted that the Murphy s PTC does not work as a good chiral catalyst for the Michael reaction of chalcone, but the same PTC effectively catalyses the epoxidation of chalcones with sodium hypochlorite (NaOCl) [24c]. Trials for the epoxidation of chalcone in the combination of hydroperoxides and modified guanidines 19 [27b] resulted in less effective asymmetric induction compared to the Murphy s PTC [53] (Scheme 4.21). 

Chinchilla, R., Najera, C. and Sanchez-Agullo, P. (1994) Enantiomerically pure guanidine-catalysed asymmetric nitroaldol reaction. Tetrahedron Asymmetry, 5, 1393-1402 Ma, D. and Cheng, K. (1999) Enatioselective synthesis of functionalized a-amino acids via a chiral guanidine-catalysed Michael addition reaction. Tetrahedron Asymmetry, 10, 713. 

Ryuda, A., Yajima, N., Haga, T. et al. (2008) ( )-l,2-Bis(2-methylphenyl)ethylene-l,2-diamine as a chiral framework for 2-iminoimidazohdine with 2-methylphenyl pendant and the guanidine-catalysed asymmetric Michael reaction of rert-butyl diphenyhminoacetate and ethyl acrylate. The Journal of Organic Chemistry, 73, 133-141. 

Kumamoto, T., Rhine, K., Endo, M. et al. (2005) Guanidine-catalysed asymmetric addition reactions Michael reaction of cyclopentenone with dibenzyl malonates and epoxidation of chalcone. Heterocycles, 66, 347-359. 

Fu, X., Jiang, Z. and Tan, C.-H. (2007) Bicyclic guanidine-catalysed enantioselectivephospha-Michael reaction synthesis of chiral P-aminophosphine oxides and P-aminophosphines. Chemical Communications, 5058-5060. 

Scheme 6.7 Chiral guanidine catalysed asymmetric Michael addition reaction of t-butyl diphenyliminoacetate with methyl vinyl ketone...

Atom economy is used as the first filter to select suitable guanidine-catalysed enantioselective reactions. Most guanidine-catalysed reactions fit well with this criterion for example, Michael reactions and its variants have perfect atom economy when the guanidine catalyst is used as a Bronsted-base catalyst. Subsequently, we apply the E-factor to give a rough guide on waste generation of these selected reactions. 

Numerous guanidine-catalysed asymmetric Michael reactions and its related variants such as aza-Michael, oxa-Michael, phospha-Michael, sulfa-Michael have been reported in the literature. A nonexhaustive selection of conjugate addition reactions that is relevant to green chemistry will be presented. Glycine imines are commonly employed in Michael additions. They are protected a-amino acids and must he deprotected if an amino acid derivative is desired (Scheme 23.5). The large molecular mass of the imine group then makes waste generation a problem. 

Feng and coworkers reported a highly enantioselective Michael reaction of p-ketoesters and nitro-olefins. Ethyl acetate, the recommended solvent, (Table 23.1), is rarely employed in guanidine catalysed asymmetric reactions. It was found to be optimal for this reaction and 2 to 5 mol% of catalyst gives excellent enantioselectivity and diastereoselectivity. The yields are generally high and a practical application of the reaction was demonstrated with a 2-g-scale synthesis of an intermediate for the synthesis of Ramipril analogues (Scheme 23.8). 

Scheme 1.71 Sulfa-Michael reactions of tert-butyl 2-phthalimido acrylates catalysed by bicyclic guanidine.

The domino Henry-Michael reaction of CH3NO2 with 7-oxo-hept-5-en-l-als RC0CH=CH(CH2)3CH=0, catalysed by the quinine-derived thiourea (288b) (<96% ee), followed by the tetramethyl guanidine (TMG)-catalysed retro-Henry-Henry reaction of the initially formed disubstituted cyclohexanols, led to a refinement of diastereoselectivity (to >99 1 dr) ... 

In 2013, Zhao et al. described a highly diastereo- and enantioselective synthesis of trisubstituted cyclohexanols based on a one-pot sequential tandem Henry-Michael reaction catalysed by a combination of a chiral cinchona alkaloid thiourea and 1,1,3,3-tetramethyl guanidine. This process occurred between nitromethane and 7-oxo-hept-5-en-l-als, providing the corresponding tandem chiral products as almost single diastereomers... 

Chiral bicyclic guanidine (221) has been identified as an excellent catalyst for reactions between anthrones (219) and various dienophiles, such as (220). The catalyst can tolerate a range of substituents and substitution patterns, making several anthrone derivatives suitable for this reaction. Both Diels-Alder and Michael adducts were obtained in excellent yields, high regioselectivities, and high enantioselectivities (<99% ee). This is the first case of a highly enantioselective base-catalysed anthrone Diels-Alder reaction.263... 

Scheme 2.34 Tandem Henry-Michael-retro-Heniy reaction catalysed by a chiral cinchona alkaloid thiourea and 1,1,3,3-tetramethyl guanidine.

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