Schiff base thioureas

Schiff base thiourea catalysts (2 mol%) first enantioselective (polymer-bound) thioureas, Strecker reactions (92% yl. 91% ee)... 

Schiff base thiourea derivative 11 incorporating the (lR,2R)-diaminocyclohex-ane unit as chiral backbone was synthesized independently in solution on the basis... 

Figure 6.15 Polymer-bound Schiff base thiourea catalyst 41 bearing 5-pivaloyl-substitution and its nonimmobilized urea analog 42 optimized for the asymmetric Strecker reaction of aromatic and aliphatic aldimines.

Scheme 6.43 Recycling study Polymer-bound Schiff-base thiourea 41 catalyzed the Strecker reaction of pivalaldimine without loss of activity or enantioselectivity even after 10 catalytic cycles.

It was found that both the replacement of the secondary amide unit with a bulkier tertiary amide and the incorporation of a thiourea moiety instead of the urea unit resulted in a significant improvement in stereoinduction (from initial 80% ee obtained with 42 to 97% ee). This led to the identification of hydrogen-bonding Schiff base thiourea catalyst 47, while the urea derivatives 43-46 gave lower ee values (Figure 6.16). 

This tertiary amide-functionalized Schiff base thiourea was found to efficiently catalyze the asymmetric Strecker reaction [157] of N-benzyl-protected aldimines and also one ketimine in high enantioselectivities (86-99% ee) and proved superior to 42 examined under the same conditions (1 mol% loading, toluene, -78 °C, HCN) (Scheme 6.46) [198]. 

Figure 6.16 Structure optimization of 42 in the asymmetric Strecker reaction of N-benzyl-protected 2-methylpropionaldehyde imine identified tertiary amide-functionalized Schiff base thiourea 47 as the most enantioselective catalyst stmcture.

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... 

A pioneer in the field of the asymmetrie (thio)urea organocatalysis was Eric Jacohsen, who first reported a chiral (polymer-hound) Schiff base thiourea derivative for asymmetric Strecker reactions optimised from parallel synthetic libraries/ These catalysts can be used either in solution or immobilised to a polystyrene resin, with the latter retaining efficiency, after repeated recycling/ The key factors responsible for high enantioselectivities were the presence of bullqr substituents at both the amino acid position and at the 3-position of the aromatic ring (Scheme 19.3). 

Systematic investigations of the catalyst structure-enantioselectivity profile in the Mannich reaction [72] led to significantly simplified thiourea catalyst 76 lacking both the Schiff base unit and the chiral diaminocyclohexane backbone (figure 6.14 Scheme 6.88). Yet, catalyst 76 displayed comparable catalytic activity (99% conv.) and enantioselectivity (94% ee) to the Schiff base catalyst 48 in the asymmetric Mannich reaction of N-Boc-protected aldimines (Schemes 6.49 and 6.88) [245]. This confirmed the enantioinductive function of the amino acid-thiourea side chain unit, which also appeared responsible for high enantioselectivities obtained with catalysts 72, 73, and 74, respectively, in the cyanosilylation of ketones (Schemes 6.84 and 6.85) [240, 242]. 

The modification of thiourea catalyst 93 through incorporation of the (S,S)-diaminocyclohexane backbone as an additional chirality element and a Schiff base imidazoyl-moiety led to the bifunctional catalyst 94 that, in contrast to 93 in the Strecker reaction (Scheme 6.99), exhibited enantioinduction (83-87% ee) in the nitro-Michael addition of acetone to trons-P-nitrostyrenes. The desired adducts were isolated in moderate yields (46-62%) as depicted in Scheme 6.100) [259]. 

Aiiiino-4-phenylthiazoles, from o-diazo-acetophenone and thiourea, 231 2-Amino-5-phenylthiazole, diuretic prope ties of Schiffs bases of, 167 synthesis of, by condensation of ammonia with At(ary 1-1,3-oxathiol-2-yIidine) tertiary iminium salts. 300 2-(p-Ammophenyl) thiazoles, syntheses of, 4,5-disubstituted derivatives of, 191 2-Amino5-substituted thiazoles, from o-haloaiddiydes and thiourea, 224, 225 /V,At -bis (2-Amino-4 substituted thiazolyl)-p biphenylene, from p-biphenylene dithiourea and o-halocarbonyl compounds, 243... 

The reactions of 2-aminobenzimidazoles have been reviewed <83S86l>. The compounds form Schiffs bases with carbonyl compounds, with isocyanates and isothiocyanates they give ureas and thioureas, they are subject to 1,3-dipolar addition reactions, and to the formation of carbamates on acylation and aroylation. When aminoimidazoles are acylated there is frequently competition between the annular and exocyclic nitrogen (see above). Add chlorides and anhydrides (soft) acylate the amino group chlorocarbonic acid esters (hard) are specific for the heteroatom <84CHE204>. When heated, the A -acyl products isomerize (Scheme 91). 

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