Thiourea derived catalysts addition

Wenzel and Jacobsen, in 2002, identified Schiff base thiourea derivative 48 as catalyst for the asymmetric Mannich addition [72] of tert-butyldimethylsilyl ketene acetals to N-Boc-protected (hetero)aromatic aldimines (Scheme 6.49) [201]. The optimized structure of 48 was found through the construction of a small, parallel... 

The Takemoto group synthesized a series ofdiaminocyclohexane-based thiourea derivatives (e.g., 12, 40, 57, and 58) for catalysis of the Michael addition [149-152] ofmalonates to trons-j3-nitrostyrenes (Figure 6.18) [129, 207]. In the model, Michael addition of diethyl malonate to trons-]3-nitrostyrene at room temperature and in toluene as the solvent tertiary amine-functionalized thiourea 12 (10mol% loading) was identified to be the most efficient catalyst in terms of catalytic activity (86%... 

Figure 6.27 Representative (R,R)-l,2-diaminocyclohexane-derived thiourea derivatives incorporating a phthalimide (Phthal) and tetraphenylphthalimide (TPhP) moiety catalyst screening was performed in the Michael addition of acetophenone-derived morpholine enamine to trans-()-nitrostyrene in toluene as the solvent.

The Jacobsen group independently focussed on the development of primary amine-functionalized thiourea derivatives and published, in 2006, the thioureas 100-103 incorporating the established tert-leucine (amide) motif (Figure 6.14) and the diaminocyclohexane or diphenylethylenediamine chiral backbone, respectively (Figure 6.31) [262]. The catalyst screening was carried out in the asymmetric Michael addition [149-152] of 2-phenylpropionaldehyde, an a,a-disubstituted aldehyde, to 1-nitrohex-l-ene (at 20mol% loading, DCM, rt, variable equiv. of H2O)... 

The Soos group, in 2005, prepared the first thiourea derivatives from the cinchona alkaloids quinine QN (8S, 9R-121), dihydroquinidine DHQD (8S, 9S-122), C9-epi-QN (8S, 9P-123), and quinidine QD (SR, 9R-124) via an experimentally simple one-step protocol with epimerization at the C9-position of the alkaloid starting material (Figure 6.39) [278]. The catalytic efficiency of these new thiourea derivatives and also of unmodified QN and C9-epi-QN was evaluated in the enan-tioselective Michael addition [149-152] of nitromethane to the simple model chal-cone 1,3-diphenyl-propenone resulting in adduct 1 in Scheme 6.119. After 99h reaction time at 25 °C in toluene and at 10 mol% catalyst loading QN turned out to be a poor catalyst (4% yield/42% ee (S)-adduct) and C9-epi-QN even failed to accelerate the screening reaction. In contrast, the C9-modified cinchona alkaloid... 

The simultaneous use of urea, or thiourea [76] and DABCO catalyst was introduced by the Connon group for the addition of methyl acrylate and benzaldehyde [39]. The study revealed that, although both ureas and thioureas accelerated the reaction relative to the uncatalyzed process, urea was superior to thiourea in terms of stability and efficiency. Chiral thiourea derivatives may offer, however, superior enantioselectivity. It was postulated, that the catalysts operate mainly via a Zimmerman-Traxler-type transition state 69 for addition of the resulting enolate anion to the aldehyde (Scheme 5.15). 

Disubstituted flavanones and chromanones are produced with good enantioselectivity from chalcones activated by an a-fert-butyl ester function through an intramolecular Michael addition catalysed by a chiral thiourea derivative. In situ decarboxylation enhances the ee and yields remain high <07JA3830>. A comprehensive study of the asymmetric cyclisation of 2 -hydroxychalcones to flavanones has refuted the ability of camphorsulfonic acid to achieve enantioselectivity but has shown that cinchona-based catalysts can be effective <07EJO5886>. 

The reaction of ( )-3,3-dimethyl-l-butene-l,2-r/2 with hydrogen cyanide and of ( )-3,3-dimethyl-l-butene-l-d2 with deuterium cyanide stereospecifically proceeds in a cis fashion with Pd(Diop)2 used as the catalyst precursor20,24. The stereochemistry of the products is verified by NMR and characterization of the thiourea derivatives of the corresponding amine obtained with lithium aluminum deuteride. No //wu-addition products exceeding a limit of 5-10% can be detected. 

With respect to aliphatic ifltrooleflns, 2-aminobenziinidazole-derived catalyst 163 [251 ] and thiourea 165 [253] have been d onstrated to catalyze the conjugate addition of 1,3-diketones to P-alkyl substituted nitrooleflns, generally with slightly... 

A different approximation was reported by Tang, Li, and co-workers [56] by using Seebach s nitroallylic acetate reagent 85, cyclohexanones, and proline-thiourea derivative XXVI as a catalyst. Nitroallylic acetate reacts with cyclohexanones via a double Michael addition, affording the final fused bicyclic ketones 86 in excellent yields and stereoselectivities (Scheme 10.24). 

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