Chiral compounds guanidines

The wide applicability of the PK reaction is apparent in the synthesis of pyrroles, for example, 45, en route to novel chiral guanidine bases, levuglandin-derived pyrrole 46, lipoxygenase inhibitor precursors such as 47, pyrrole-containing zirconium complexesand iV-aminopyrroles 48 from 1,4-dicarbonyl compounds and hydrazine derivatives. The latter study also utilized Yb(OTf)3 and acetic acid as pyrrole-forming catalysts, in addition to pyridinium p-toluenesulfonate (PPTS). 

Terada and co-workers reported a novel guanidine catalyst with a chiral binaphthol backbone for the asymmetric addition of dicarbonyl compounds to nitro-olefins [126]. Substitution on the binaphthol backbone dramatically increased enantioselectivity. 

Enantioselective a-animation of carbonyl compounds has been promoted by l-azetidinecarboxylic acid,159 axially chiral guanidine derivative,160 and chiral palladium complexes.161... 

The axially chiral guanidine catalyst (155) (0.4-5 mol%) has been developed to facilitate the highly enantioselective Michael addition of 1,3-dicarbonyl compounds (g to a broad range of conjugated nitroalkenes (<98% ee).211... 

Guanidines have been implemented early as recognition elements, guided by the apparent function of arginine in protein structures. The C2-symmetric, chiral anion receptor 52 was introduced by Lehn, Schmidtchen and de Mendoza consecutively and studied in various modifications (Scheme 13) [23c]. For example, an elaborate system based on 52 provided reasonable enantioselective recognition of amino acids [23c, 28]. Furthermore, bis(guanidinium) compounds catalyze RNA hydrolysis in the presence of external base via phosphodiester complexation [29]. The,se functional elements were joined in receptor 53 to yield a functional transesterification catalyst [30]. 

In the kinetic resolution of 1-indanol with diphenylphosphoryl azide in dichloromethane (DCM) using modified guanidine [68], (7 )-excess azide compound was produced in 58% yield with 30% ee after six hours when a C2-symmetrical bicyclic guanidine 13 [37] was used as a chiral auxiliary (Scheme 4.26). 

Terade, M., Nakano, M. and Uhe, H. (2006) Axially chiral guanidine as highly active and enantioselelctive catalyst for electrophilic amination of unsymmetrically substituted 1,3-dicarbonyl compounds. Journal of the American Chemical Society, 128, 16044-16045. 

Ishikawa, T., Araki, Y, Kumamoto, T. era/. (2001) Modified guanidines as chiral supedrbases apphcation to as3munetric Michael reaction of glycine imine with acrylate or its related compounds. Chemical Communications, 245-246. 

In this chapter, applications of amidine, guanidine and phosphazene superbases to the synthesis of natural products have been discussed. Many structurally complex natural products have been synthesized efficiently and elegantly by making use of the reactions described. Currently, much attention is focussed on the development of chiral superbases and their application to asymmetric reactions. Such catalytic asymmetric reactions are expected to offer exciting and efficient new approaches to the synthesis of natural products and biologically active compounds. 

Scheme 4.33 Chiral guanidine-catalyzed enantioselective Michael addition of 1,3-dicarbonyl compounds to enones.

Both chiral tertiary amine-(thio)ureas 20 [39] and 21 [40] have been able to catalyze the a-amination of 3-ketoesters in excellent yields and high enantioselec-tivity. In these reactions, cyclic 3-ketoesters performed optimum while the acyclic counterparts reacted very slowly, giving very low ee. A transition state model involving dual activation of substrates is supported by DFT calculations [42]. The axially chiral guanidine 22 is another highly active catalyst for a-amination of various cyclic and acyclic 1,3-dicarbonyl compounds. 

More recently, Tan and co-workers reported the reaction of p,7-unsaturated thioesters with di-tert-butyl azodicarboxylate promoted by the chiral guanidine 32 as the Br0nsted base catalyst (Scheme 11.16) [57]. By judicious choice of the double bond geometry of the (3,y-unsaturated thioester compound, the reaction can deliver either enantiomeric product with excellent enantioselectivity. 

Electrophilic amination of 1,3-dicarbonyl compounds were catalyzed by an axially chiral seven-membered guanidine (24) with low catalyst loading (Scheme 2.65) [125]. 

A general procedure for the Michael addition cata-iyzed by chiral guanidine. EtsN (0.2 mL, as solvent) was added to a mixture of 1,3-dicarbonyl compounds (0.06 mmol) and guanidine (2.24 mg, 0.01 mmol). After cooling the mixture at —20°C for about 0.5 hours, 2-cyclo-penten-l-one (4.2 mL, 4.2 mg, 0.05 mmol) was added. The reaction mixture was monitored by thin layer chromatography (TLC), and after complete consumption of enone, the solvent was removed under vacuum. The cmde product was directly loaded onto a short silica gel column, followed by... 

Reviews have featured recent applications of organocatalysts to asymmetric aldol reactions, including particular focus on catalysis by small molecules. The effects of introduction of a diaryl (oxy)methyl group into chiral auxiliaries, catalysts, and dopants have been discussed and applications of amidine-, isothiourea-, and guanidine-based nucleophilic catalysts for a range of reactions of carbonyl compounds have been highlighted. " ... 

---