Thiourea catalysis amine-thioureas

Chiral amines and diamines are readily available substrates for the synthesis of ligands for transition metal-catalysed reactions since they can easily be transformed into chiral ureas and thioureas. Therefore, several groups have prepared chiral symmetrical ureas and thioureas, dissymmetrical ureas and thioureas, amino-urea and thiourea derivatives. Finally polyureas and non-soluble polythioureas were also prepared and tested as ligands for asymmetric catalysis. 

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%... 

The Tsogoeva group, in 2006, reported the introduction of newly designed bifunctional secondary amine-functionalized proline-based thioureas (95 and 96) and the primary amine-functionalized thioureas (97-99) for catalysis of the asymmetric addition of ketones to trans-P-nitrostyrenes (Figure 6.30) [260, 261]. Using... 

Scheme 6.102 Bifunctional catalysis with primary amine thiourea 99 Proposed transition states to explain the onfi-diastereoselectivity (A) and the syn- diastereoselectivity (B) of the Michael addition of both acylic and cyclic ketones to frans-P-nitrostyrene.

Catalysis by other nucleophiles has also been found for secondary aliphatic amines, e. g., by thiocyanate (Fan and Tannenbaum, 1973), and by thiourea and its tetramethyl derivative (Meyer and Williams, 1988, and earlier investigations mentioned there). The results are comparable to those of aromatic diazotizations (Zollinger, 1994, Sect. 3.3). 

A -Aroyl-A -substituted thiourea derivatives have been prepared from reaction of aroyl isothiocyanate with amines under solid-liquid phase transfer catalysis condition using polyethylene glycol-400 (PEG-400) as catalyst. Reaction of isothiocyanates with lithiated chiral secondary amines has provided chiral thioureas (Scheme 40). °... 

Anthrones [204] and 3-substituted oxindoles [205] possess activated methylenes which have been able to react under asymmetric iminium catalysis with a,p-unsaturated aldehydes. The reaction with 3-substituted oxindoles is especially attractive, since chiral quaternary stereocenters are generated. For this purpose, chiral primary amine thiourea catalyst 132 has been demonstrated as a very efficient promoter for the addition of 3-alkyl substituted oxindoles to P-aryl substituted enals in the presence of benzoic acid as cocatalyst in toluene at rt to afford the corresponding Michael adducts in good diastereoselectivities (dr up to >19/1) and good enantioselectivities (73-93% ee) (Scheme 2.75) [205a], P-Alkyl substituted enals are not suitable partners for the reaction affording very low diastereo- and enanti-... 

In many examples of Brpnsted base catalysis, the combination of a chiral tertiary amine and a hydrogen-bonding donor, such as a urea or thiourea moiety, significantly enhances the selectivity of the formation of carbon-carbon bonds. Catalysts possessing this combination of functional groups have proven useful due to their ability to simultaneously stabilize and activate both electrophilic and nucleophilic components. 

Later, Melchiorre and coworkers accomplished a challenging direct vinylogous aldol reaction of 3-methyl-2-(yclohexen-l-one with a-keto esters utilising a bifunctional primary amine-thiourea. Catalyst 48 based on the (l/ ,2/ )Kiiphenylethylene-l,2-diamine backbone combined with benzoic acid as cocatalyst promoted the reaction by means of a concomitant activation of both reacting partners (see TS in Scheme 19.55), the ketone via dienamine catalysis and the ester via hydrogen-bonding interactions (Scheme 19.55). 

The asymmetric a-allqrlation of carbonyl compounds constitutes one of the fundamental organic transformations for the construction of carbon-carbon bonds, and has long been the Achilles heel for asymmetric aminocatalysis. Towards a solution to this long-standing problem, Jacobsen and coworkers have shown that the enantioselective a-allqrlation of a-arylpropionaldehydes with diarylbromonethane can be carried out under the catalysis of primary-amine thiourea 39 (Scheme 19.60). Catalyst 39 reacted with the aldehyde to form an enamine, followed by a S -l-type substitution induced by the bromide anion. 

FIGURE 2.41. Takemoto s (A) and Papai s (B) alternative transition states for the bifunctional amine-thiourea catalysis of Michael addition to nitroolelins. 

Enantioselective organocatalytic a-chlorination of aldehydes, via enamine catalysis, was independently reported by the groups of MacMillan and Jprgensen in 2004 (Scheme 13.20) [46, 47]. MacMillan utilized his imidazolidinone catalyst and a perchlorinated quinone as the chlorine source, to obtain the S-enantiomer of the a-chloroaldehyde products. Jprgensen employed NCS as the chlorine source, and either a prolinamide catalyst to access the / -enantiomer of the a-chloroaldehyde products, or a Ci-symmetric amine catalyst to access the 5-enantiomer. A recyclable fluorous pyrrolidine-thiourea bifunctional organocatalyst was later employed as an enamine catalyst in this transformation [48]. 

In a similar manner, conjugate addition of azlactones possessing isopropyl or isobutyl groups at the C4-position to a series of acyl phosphonates proceeded with y-selectivity and high stereoselectivity under the catalysis of quinine-derived thiourea 19c. The phosphonate moiety of the resulting adducts was readily replaced with various heteronucleophiles such as alcohols and amines in situ under the influence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Scheme 17) [33]. The synthetic utility of azlactones as an acyl anion equivalent in this y-selective addition... 

The catalytic potential of base functionalities has been referred to in the previous chapter (see Sect. 7.4), wherein the interplay between an acidic (thio-)urea and a basic amine separated by a chiral linker was shown to enable the simultaneous activation of both the electrophile and nucleophile. In addition to such brfunctional thiourea-containing acid-base catalysts, chiral catalysts containing Lewis or Br0nsted-) base functionality as the sole catalyticaUy active group as weU as those having another H-bond donor like a hydroxy group e.g. Cinchona alkaloids) have found widespread applications in asymmetric catalysis (443-449). 

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