Guanidines thioureas

Figure 6.55 Uncharged tris-thiourea 190 without guanidinium moiety and charged guanidinium structure 191 without a thiourea group appeared catalytically inactive in the Henry reaction of cyclohexane carboxaldehyde with nitromethane, while guanidine-thiourea 183 gave 99% yield and 95% ee under identical (optimized) conditions.

Scheme 6.168 Syntheses of 4-ep/-cytoxazone and cytoxazone utilizing guanidine-thioureas 183 and 186 for the initial asymmetric Henry reaction step.

Scheme 6.169 Screening reaction to identify (R,R)-configured guanidine-thiourea 186 as matching catalyst for the anti-diastereoselective and enantioselective Henry reaction of (S)-a-amino aldehydes with nitromethane.

Utilizing 10mol% of (R,R)-guanidine-thiourea catalyst 186 under optimized biphasic condihons for the Henry reaction [224] of (S)-a-amino aldehydes with nitromethane furnished the corresponding nitroalcohols 1-6 in yields ranging from 33 to 82% and with excellent diastereoselechvities (up to 99 1 anti/syn) and enanhoselectivihes of the major isomer (95-99% ee) (Scheme 6.171) [328]. 

Scheme 6.170 Suggested transitions states for the anti-diastereoselective Henry (nitroaldol) reaction promoted by (R,R)-catalyst 186 (TS 1) and its (S,S)-isomer 183 (TS 2) to demonstrate the match/mismatch relationship between guanidine-thiourea catalyst and (S)-a-aldehyde.

Scheme 6.173 Proposed transitions-state geometry for the nitroaldol reaction of nitroalkanes with a-ketoesters in the presence of (S,S)-configured guanidine thiourea 183.

Other amidine components are arranged according to their reactivity guanidine thiourea > dicyandiamide > acetamidine > S-methylisothiourea > urea. 

Ambident nucleophiles, such as guanidine, thiourea, and urea attack 1,3-dimethyluracil first at the 6-position. After cleavage of the uracil ring and displacing ring closure, novel pyrimidines are formed extruding di-... 

Guanidines. Thioureas containing at least one electron-withdrawingiV-substituent are... 

Instead of the ester function as in the examples above, a (dimethylamino)methylene group may be used in a similar way to incorporate a carbon atom into the pyrimidine part of 5,6-dihy-dropyrido[.3.4-<7 pyrimidin-8(7//)-oncs. The reaction of 4-[(iV,A -dimethylamino)methylenc]-piperidine-2,3-dione (14) with guanidine, thiourea, or acetamidine yields the corresponding 5,6-dihydropyrido[3,4- /]pyrimidin-8(7//)-one 15 in low yield.474... 

Catalytic enantio- and diastereoselective nitroaldol reactions were explored by using designed guanidine-thiourea brfunctional organocatalysts like 15 (Figure 4.4) under mUd and operationally simple biphasic conditions. These catalytic asymmetric reactions have a broad substrate generality with respect to the variety of aldehydes and nitroalkanes [43]. On the basis of studies of structure and catalytic activity relationships, a plausible guanidine-thiourea cooperative mechanism and a transition state of the catalytic reactions are proposed. 

Figure 4.4 Structure of guanidine-thiourea bifunctional organocatalyst 15...

Scheme 2.46 Nitroaldolisations of a-keto esters catalysed by guanidine-thiourea.

Sohtome, Y Hashimoto, Y Nagasawa, K. Guanidine-Thiourea Bifunctional Organocatalyst for the Asymmetric Henry (Nitroaldol) Reaction. Adv. Synth. Catal. 2005,347,1643-1648. 

Finally, a new guanidine-thiourea has been developed to further expand the Takemoto s family of organocatalysts, and applied to the addition of malonates to nitroalkenes. DFT calculations, including solvent effects and dispersion corrections, were employed to formulate a plausible mechanism. ... 

Conformationally flexible guanidine-thiourea catalyst 174 has unique solvent-dependent properties in the catalytic Mannich-type reaction. Based on detailed kinetic analyses, the origin of solvent-dependent stereo-discrimination is controlled by enthalpy-entropy compensation. The stereoselectivities of (S)-selective Mannich-type reactions in non-polar solvents such as m-xylene are predominantly due to differences in the entropies of activation (Table 28.9, entries 1-3), whereas the stereo-discrimination of (R)-selective reactions in polar solvents such as acetonitrile result from differences in the enthalpies of activation (Table 28.9, entries 4-6) [89]. 

Sohtome Y, Hashimoto Y, Nagasawa K. Diastereoselective and enantioselective Henry (nitroaldol) reaction utilizing a guanidine-thiourea bifunctional organocatalyst. Eur. J. Org. Chem. 2006 2894-2897. 

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