Urea catalysts

Meanwhile, chiral (thio)urea catalysts have been employed for a variety of imine addition reactions consisting of Mannich, aza-Henry, Pictet-Spengler, and hydrophosphonylation reactions. ... 

The asymmetric Mannich addition of carbon nucleophiles to imines catalyzed by the cyclohexane-diamine catalysts has developed significantly in the past decade. List and co-workers reported the asymmetric acyl-cyanantion of imines catalyzed by a cyclohexane-diamine catalyst [103], Using a derivative of Jacobsen s chiral urea catalyst, the authors optimized reaction conditions and obtained chiral iV-acyl-aminonitriles in high yield and enantioselectivities (Scheme 51). The scope of the reaction was explored with both aliphatic and aromatic imines, providing good to high selectivities for a variety of substrates. 

Schreiner[1,114,125] guidelines for (thio)urea catalyst structure design, DA reactions and 1,3-dipolar cycloadditions ("catalytic amount" 1 mol% 12)... 

Figure 6.3 Stereoselective, chiral thiourea derivatives of achiral benchmark thiourea organocatalyst N,N -bis [3,5-(trifluoromethyl)phenyl]thiourea 9 stereoselective hydrogen-bonding thiourea organocatalysts incorporating the privileged 3,5-bis(trifluoromethylphenyl)thiourea moiety. The (thio)urea catalyst structure is the leitmotif for the chapter organization.

Urea 32, the bis-(mono-trifluoromethyl)phenyl derivative of urea catalyst 16 [178], was reported to operate as double hydrogen-bonding organocatalyst in the diastereoselective synthesis of y-butenolide products substituted at the y-position... 

Scheme 6.36 Products obtained from the addition of indols to various styrene oxides in the presence of N-tosyl urea catalyst 37.

Scheme 6.37 Product range of the styrene oxide opening with anilines promoted by N-tosyl urea catalyst 37.

Figure 6.12 Polystyrene-bound Schiff base (thio)urea catalysts HTS-optimized in the asymmetric Strecker reaction between N-allyl-protected benzaldimine and TBSCN key results obtained from the different libraries.

Scheme 6.89 Proposed mechanistic picture for the asymmetric alcoholytic DKR of racemic aziactones promoted by bifunctional (thio)urea catalysts 64, 77, and 78 (A) hydrogen-bonded azlactone-64 complex supported by NMR methods (B).

Based on the modular structure of Schiff base catalysts such as first-generation Strecker urea catalyst 42 [196, 198] (Figure 6.15 Schemes 6.41 and 6.45), Yoon... 

Figure 6.40 (Thio)urea catalysts derived from dihydroquinine and dihydroquinidine screening results obtained from the asymmetric Michael addition of dimethyl malonate to frans-p-nitrostyrene.

Thio)urea Catalysts Derived from Chiral Amino Alcohols... 

Figure 6.59 Structural modifications of glucosamine-derived urea catalysts screening in the formation of Strecker adduct 12 (Scheme 6.174).

Fig. 3. Solvent effect on the yield of 2-phenylpyrrole [89KGS29I] I, DMSO 2, HMPA 3, l-methyl-2-pyrrolidone 4, sulfolane 5, PEG 6. tetramethyl urea. Catalyst KOH (0.5 mol/L), for other reaction conditions see Fig. 1.

For related chiral (thio)urea catalyst-mediated electrophilic activation of... 

Cyclohexanediamine-derived amine thiourea 70, which provided high enantio-selectivities for the Michael addition [77] and aza-Henry reactions [78], showed poor activity in the MBH reaction. This fact is not surprising when one considers that a chiral urea catalyst functions by fundamentally different stereoinduction mechanisms in the MBH reaction, and in the activation of related imine substrates in Mannich or Streclcer reactions [80]. In contrast, the binaph-thylamine thiourea 71 mediated the addition of dihydrocinnamaldehyde 74 to cyclohexenone 75 in high yield (83%) and enantioselectivity (71% ee) (Table 5.6, entry 2) [79]. The more bulky diethyl analogue 72 displayed similar enantioselectivity (73% ee) while affording a lower yield (56%, entry 3). Catalyst 73 showed only low catalytic activity in the MBH reaction (18%, entry 4). 

Cook reported that a 3,3 bis(trifluoromethyl) BINOL catalyzed asymmetric addition of allylindium to hydrazones proceeds in modest to good enantioselec tivities (10 92% ee) [90]. The stoichiometric version of this reaction yields much higher enantioselectivities (84 97% ee). Jacobsen later found that a chiral urea catalyst is effective in catalyzing a similar transformation [96]. The bifunctional catalyst 55 bearing a hydrogen bond donor and a Lewis base that are properly... 

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