Thiourea catalysts 1-phenyl

In 2003, Takemoto and co-workers introduced the first tertiary amrne-function-ahzed thiourea catalyst [129]. This new type of stereoselective thiourea catalyst incorporating both (R,R)-l,2-diaminocyclohexane as the chiral scaffold and the privileged 3,5-bis(trifluoromethyl)phenyl thiourea motif for strong hydrogen-bonding substrate binding, marked the introduction of the concept of bifunctional-... 

The asymmetric alcoholytic ring opening of 4-substituted-2-phenyl-4,5-dihydro-l,3-oxazin-6-ones proved to be a efficient method for the preparation of enatiomerically pure /3-amino acid derivatives <2005AGE7466>. Treatment of 2,4-diphenyl-4,5-dihydro-l,3-oxazin-6-one 208 in the presence of the bifunctional chiral thiourea catalyst 211 resulted in formation of an enantiomerically enriched mixture of the unchanged oxazinone (iJ)-208 and allyl (4)-3-benzoyl-amino-3-phenylpropanoate 209. The resolved material (iJ)-208 and the product 209 could easily be separated by a selective hydrolytic procedure that converted oxazinone (iJ)-208 quantitatively into the insoluble iV-benzoyl /3-amino acid 210 (Scheme 37). 

Nagasawa and co-workers reported the use of a chiral bis-thiourea catalyst (108) for the asymmetric MBH reactions of cyclohexenone with aldehydes [95]. Since others had already shown that thioureas form hydrogen bonds with both aldehydes and enones, it was hypothesized that the inclusion of two thiourea moieties in close proximity on a chiral scaffold would organize the two partners of the MBH reaction and lead to enantiofacial selectivity. Initial studies showed that the achiral 3,5-bis-(trifluoromethyl)phenyl-substituted urea increased the rate of MBH reaction between benzaldehyde and cyclohexenone. These authors then showed that chiral 1,2-cyclohexyldiamine-linked bis-thiourea catalyst 108, used at 40 mol% loading in the presence of 40 mol% DMAP, promoted the MBH reactions of cyclohexenone with various aliphatic and aromatic aldehydes (40) to produce allylic alcohols in moderate to high yields (33-99%) and variable enantio-selectivities (19-90% ee Table 6.33). 

The heterogeneous version of this reaction was quite recently reported by Guo and coworkers [75]. Highly interestingly, in the reaction of the indole with the N-Bs (Bs, benzene sulfonyl) phenyl imine 162, enhanced enantioselectivity (99.2% ee at 40 °C) compared with that (92% ee at 50 °C [74], 93.2% ee at 40 °C [75]) obtained with the homogeneous analogue 40 was achieved using the mesoporous silica (SBA-15) supported epi-quinine thiourea catalyst 161. The increased ee value can be ascribed to the confinement effect [76] of the support (Scheme 8.64). 

Schreiner et al. developed thiourea catalyst as a promising hydrogen donor, which has more benefit in solubility, synthesis and catalytic mrn over number compared with urea catalyst, in the Diels-Alder reaction of A-crotonyloxazolidinone and cyclopentadiene [22,23] (Table 9.7). A,A -Di[3,5-bis(trifluoromethyl)phenyl]thiourea accelerates the reaction and improves stereoselectivity (run 4) similar to a metal catalyst such as aluminium chloride (AICI3) (mn 2) or titanium chloride (TiCls) (run 3). 

A more simple thiourea catalyst with amino functionality catalyses the asymmetric Michael addition of 1,3-dicarbonyl compound to nitroolefin [29,30]. In the reaction of malonate to nitrostyrene (Table 9.11) the adduct is satisfactorily obtained when A-[3,5-bis(trifluor-omethyl)phenyl]-A -(2-dimethylaminocyclohexyl)thiourea is used as a catalyst (ran 1), whereas the reaction proceeds slowly when the 2-amino group is lacking (ran2). In addition, chiral amine without a thiourea moiety gives a poor yield and enantioselectivity of the product (run 3). These facts clearly show that both thiourea and amino functionalities are necessary for rate acceleration and asymmetric induction, suggesting that the catalyst simultaneously activates substrate and nucleophile as a bifunctional catalyst. 

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.

Ricci and co-workers introduced a new class of amino- alcohol- based thiourea derivatives, which were easily accessible in a one-step coupling reaction in nearly quanitative yield from the commercially available chiral amino alcohols and 3,5-bis(trifluoromethyl)phenyl isothiocyanate or isocyanate, respectively (Figure 6.45) [307]. The screening of (thio)urea derivatives 137-140 in the enantioselective Friedel-Crafts reaction of indole with trans-P-nitrostyrene at 20 °C in toluene demonstrated (lR,2S)-cis-l-amino-2-indanol-derived thiourea 139 to be the most active catalyst regarding conversion (95% conv./60h) as well as stereoinduction (35% ee), while the canditates 137, 138, and the urea derivative 140 displayed a lower accelerating effect and poorer asymmetric induction (Figure 6.45). The uncatalyzed reference reaction performed under otherwise identical conditions showed 17% conversion in 65 h reaction time. 

In 2006, Chen and coworkers reported that cinchona-based thioureas (79a or 81b) serve as catalysts for the Michael addition of a-phenyl cyanoacetate (94) to phenyl vinyl sulfone (177) at room temperature, affording the addition product 178. Nearly quantitative yields were obtained. However, the obtained ee values were only moderate (43-54% ee) (Scheme 9.62) [55]. 

Substituted biguanides (19) also react with benzil on heating in alcohol in the absence of any catalyst to give 2-substituted guanilydene-5,5-diphenylhydantoins (20), whose formation involves an anionotropic migration of a phenyl group.41 N-Amidino-O-alkylisoureas and 1-aryl- or 1-alkyl-3-amidino-2-thioureas behave similarly.42... 

DHPM derivatives 246 having phenyl moieties at C-5 and C-6 were prepared by a microwave-assisted, three-component one-pot condensation of an aromatic aldehyde, deoxybenzoin 245 and urea or thiourea, using TMSCl and Co(OAc)2 4H20 as Lewis acid catalyst (Scheme 94) (09PS1796). 

Fig. 3.10 Thiourea-based organocatalysts. a-c Chemical structure of the bifunctional thiourea-tertiary amine catalyst, bis(3,5-trifluoromethyl)phenyl cyclohexylthiourea (thiourea), and N,N-dimethylcyclohexylamine (Moditied from Dove et til. [42]). d Proposed dual activation pathway of lactide ROP [41] (Adapted with permission from Pratt et al. [41]. Copyright 2013 American Chemictil Society)...

The superbase DBU was chosen as catalyst for the ROP of lactide because of its fast kinetics, high efficiency, and prevention of transesterification. However, it was decided to add bis(3,5-trifiuoromethyl)phenyl cyclohexylthiourea (thiourea) as co-catalyst to further increase the efficiency and overcome possible steric hindrance arising from the bulkiness of macromolecular initiators. The thiourea was synthesized according to Pratt et al. [41]. Briefly, 3,5-bis(trifluoromethyl)phenyl isothiocyanate (3.37 ml, 18.5 mmol) and anhydrous tetrahydrofuran (20 ml) were added to a flame-dried two-neck round bottom flask. Cyclohexylamine (2.11 ml, 18.5 mmol) was added dropwise via a syringe at room temperature to the stirring solution. After... 

Kaupp et al. employed ball-milling technique to transform thioureas 79 by reaction with phenacyl bromide to 2-amino-4-phenyl-thiazole-hydrobromides 80 in quantitative yields from stoichiometric mixtures of the reagents at room temperature (Scheme 4.21) [14]. In soUd-state conditions, base catalyst was not needed. The water formed in the reaction does not hydrolyze phenacyl bromide under applied mild conditions and was removed by heating at 80°C in vacuo. When the same reaction was performed in a melt at 110°C, partial hydrolysis occurred, which diminishes yield, while yields obtained in solntion were lower (80-90%). This Hantzsch thiazole synthesis starts with nucleophilic snbstitution on snlfur and formation of the carbon-sulfur bond (S-alkylation), followed by further reaction cascade which results in heterocychc ring. 

An aq. soln. of thiourea dioxide and NaOH added to a stirred mixture of methyl phenyl N-tosylsulfilimine, hexadecyltributylphosphonium bromide as phase transfer catalyst, and isopropyl ether, then stirred 4 hrs. at 70° -> methyl phenyl sulfide. Y 93%. F. e., sdso mercaptans from disulfides (cf. Synth. Meth. 14, 63), s. G. Borgogno, S. Colonna, and R. Fomasier, Synthesis 1975, 529 formulas s. Synth. Meth. 30, 700. 

Schreiner and Wittkopp based on theoretical and experimental studies, developed N,N -bis[3,5-bis(trifluoromethyl)phenyl] thiourea 8, also known as Schreiner s thiourea. Initially, its catalytic activity was examined in a series of Diels-Alder reactions and 1,3-dipolar cycloaddtions. Interestingly, the effectiveness of the catalysts was substituent-dependent, rather than reactant or solvent dependent. In addition, a rigid thiourea is more effective than one with flexible substituents (Scheme 19.6). 

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