Mannich reaction between ketene silyl

Diastereoselective Mannich-type reactions between ketene silyl acetals and chiral sulfinimines using simple metal-free Lewis bases such as tetraalkylammonium car-boxylates have been reported. The sulfinimine can even be generated in situ (from aldehyde and a chiral sulfonamide), using cesium carbonate, followed by addition of ketene silyl acetal at -78 °C, and as little as 1 mol% of catalyst.32... 

In the addition of indole toiV-benzoyl aldimines, 3 also can be put to use. The catalyst IF is for promoting reaction between ketene silyl acetals and A-(o-hydroxyphenyl)aldimines, ° and the 3,3 -dimesityl analogue for vinylogous Mannich reaction. The imines are suitably activated as shown below. 

Mannich reaction. Reaction between ketene silyl acetals and aldimines occurs in the presence of sulfated zirconia in MeCN at room temperature. The reusable solid catalyst is easily recovered. 

In 2004, Akiyama s and Terada s groups independently pioneered the development of chiral BINOL-derived phosphoric acids 197, which have subsequently found wide resonance as catalysts in various asymmetric transformations [33, 41, 42]. Akiyama reported that silyl ketene acetals such as 237 participate in additions to aromatic aldimines with high diastereo- and enantioselectivity in the presence of catalyst 238 (Equation 21) [146]. In parallel studies, Terada demonstrated that the chiral phosphoric acid 242 readily catalyzes direct asymmetric Mannich reactions between acetylacetone (241) and N-Boc-protected aromatic aldimines such as 240 (Equation 22) [145]. 

Several procedures for a one-pot Mannich-type reaction in water to give (3-amino carbonyl compounds catalyzed by either Lewis acid or Bronsted acid with or without addition of surfactants have been developed. The reactions are high yielding however, the diastereoselectivities are moderate. The HBF4-catalyzed reaction between aldimines and ketene silyl acetals in a water/SDS mixture provides high stereoselectivity with very good yields (Scheme 5.19). 

Ketimines and aldimines proved to be good substrates [73]. Based on the structure modification, nuclear magnetic resonance (NMR) study, kinetic study, and computational study, they proposed a double hydrogen bond structure between the acidic N-H protons and the imine lone pair to activate the electrophile toward the attack by the cyanide ion (Figure 2.15) [74]. The catalyst system is applicable to the Mannich-type reaction of N-Boc-aldimine with ketene silyl acetals to give corresponding P-amino esters in 86-98% ee (Scheme 2.25) [75]. Hydrophospho-nylation of aldimines with bis(2-nitrobenzyl)phosphite by means of (4d) furnished a-amino phosphonates in good enantioselectivity (Scheme 2.26) [76]. 

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