Thiourea asymmetric induction

Chiral thioureas have been synthesized and used as ligands for the asymmetric hydroformylation of styrene catalyzed by rhodium(I) complexes. The best results were obtained with /V-phenyl-TV -OS )-(l-phenylethyl)thiourea associated with a cationic rhodium(I) precursor, and asymmetric induction of 40% was then achieved.387,388 Chiral polyether-phosphite ligands derived from (5)-binaphthol were prepared and combined with [Rh(cod)2]BF4. These systems showed high activity, chemo- and regio-selectivity for the catalytic enantioselective hydroformylation of styrene in thermoregulated phase-transfer conditions. Ee values of up to 25% were obtained and recycling was possible without loss of enantioselectivity.389... 

Dixon et al. screened cinchonine-derived thioureas 117-120 for their performance in the dimethyl malonate Michael addition to tra s-(5-nitrostyrene in dichlo-romethane at room temperature and at -20°C [274]. As shown in Figure 6.38, all candidates revealed comparable activity, but monodentate hydrogen-bond donor 118 exhibited very low asymmetric induction producing the desired Michael... 

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. 

The Michael reactions [149-152] between cyclohexanone and trons-nitroalkenes were also explored by Xiao and co-workers utilizing bifunctional pyrrolidine-thiourea 213 and the pyrrolidine-thioureas 214-217 (Figure 6.61) [344]. The model Michael reaction between cyclohexanone and trons-nitrostyrene identified water as the best solvent and 217 to be the most efficient catalysts concerning the activity and asymmetric induction (90% yield 96% ee dr 98 2 in 12 h at 35 °C) in the presence of benzoic acid (10mol%) as additive. The optimized catalytic system allowed the formation of a broad spectrum of Michael adducts such as 1-6 resulting from... 

Electron-deficient oxazoline thiourea 222 turned out to be the most effective catalyst concerning activity (93% yield/48h/THF) and asymmetric induction (88% ee/rt) in contrast to 218-221, which gave poor results (Figure 6.62). The solvent screening revealed aprotic THF to be the solvent of choice, while polar prohc... 

In 2006, Scheidt and coworkers [44] reported the first enantioselective direct nucleophilic addition ofthe silylated thiazolium salt 148, a precursor of the equivalent acyl anion, to nitroalkene 149 in the presence of tetramethylammonium fluoride (TMAF) and stoichiometric amounts of quinine-based thiourea 81b, producing the chiral [3-nitroketone 150 in 67% yield and with 74% ee (Scheme 9.51). The acyl anion equivalent 152 can be generated by the desilylation of 148 with TMAF, followed by the 1,2-H shift of the resulting alkoxide 151. The observed asymmetric induction indicates that there is a strong interaction between the thiourea and the nitroalkene during the carbonyl anion addition step. 

The scope of this reaction was also examined, and selected results were summa rized in Table 13.8. Control experiments demonstrated that the ee ofthe product was independent of the reaction time and that racemization of the product or autoca talysis was not probable for this catalytic system. Moreover, when the thiourea group in 25a was removed, both the catalytic activity and the level of asymmetric induction became significantly lower. Thus, introducing a thiourea group to the catalyst was pivotal to accelerate the reaction rate and improve the enantioselectivity of the product. Based on the observation and earlier reports, a rational mechanism was also proposed based upon NMR spectroscopic investigations. 

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. 

Thiourea catalyst with additional thoiurea functionality can act as possible bifunctional thiourea catalyst due to the hydrogen bonding ability of the thiourea function. C2-symmetric bisthiourea has been applied to the Baylis-Hillman reaction of cyclohexenone [42] (Table 9.14). Adduct is obtained in moderate to good yields (runs 1-6), but asymmetric induction is dependent upon the aldehyde electrophile (90% ee in run 6). The use of monothiourea as a catalyst results in low conversion (20%). Thus, it could be reasonably deduced that each thiourea function of bisthiourea independently and effectively interact with cyclohexenone and aldehyde in the transition state (Figure 9.10). 

Catalytic Asymmetric Induction with Chiral Thioureas... 

The thiourea derived from the chiral vinyl sulphoxide sulphoraphene (60), a constituent of radish seeds, undergoes cyclization to give unequal amounts of diastereoisomer (61) and its epimer, a consequence of asymmetric induction in the intramolecular addition reaction. ... 

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