Catalyst guanidine

The chiral guanidine s role as a strong Brpnsted base for the reactions of protic substrates has been proposed. In 1999, Corey developed a C -symmetric chiral guanidine catalyst to promote the asymmetric Strecker reaction [117]. The addition of HCN to imines was promoted high yields and high enantioselectivities for both electron-withdrawing and electron-donating aromatic imines (Scheme 64). 

The group proposed that the hydrocyanate underwent a formal Brpnsted base interaction with the guanidine catalyst, thus activating the nucleophile for addition (Fig. 9). In contrast to the bifunctional catalysts, the guanidines are basic enough to activate the substrates without the need for secondary moieties. 

Ma and co-workers extended use of chiral guanidine catalysts to the addition of glycine derivatives to acrylates [121], Addition products were achieved in high yield with modest enantioselectivity (Scheme 67). The ferf-butyl glycinate benzophenone imines generally provided better enantiomeric ratios than the ethyl glycinate benzophenone imines. Based on this observation, the authors hypothesized that an imine-catalyst complex determines the stereochemical outcome of the product. 

Another structurally modified guanidine was reported by Ishikawa et al. as a chiral superbase for asymmetric silylation of secondary alcohols [122]. Soon after, Ishikawa discovered that the same catalyst promoted asymmetric Michael additions of glycine imines to acrylates [123]. The additions were promoted in good yield and great asymmetric induction under neat reaction conditions with guanidine catalyst 250 (Scheme 68). The authors deduced that the high conversion and selectivity were due to the relative configuration of the three chiral centers of the catalyst in... 

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. 

Terada expanded the phospha-Michael reaction to include diphenyl-phosphites [128]. A novel binaphthol-derived guanidine catalyst promoted the addition in high yields and enantioselectivities (Scheme 73). Functionalizing the external nitrogen with a diphenylmethine moeity enhanced selectivities for a large scope of nitro-olefm derivatives. 

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... 

Scheme 7. Asymmetric Strecker synthesis with chiral guanidine catalyst 19 (Corey and Grogan).

Corey and co-workers reported the use of a C2-symmetric guanidine catalyst (53) for the Strecker reactions of N-benzhydryl aldimines [65]. The catalyst is be-... 

Vanaken, E., Wynberg, H. and Vanbolhuis, F. Nitroalkanes in C-C bond forming reactions - A crystal-structure of a complex of a guanidine catalyst and a nitroalkane substrate, J. Chem. Soc., Chem. Commun., 1992, 629-630. 

Blanc, A. C., Macquarrie, D. J., Valle, S., Renard, G., Quinn, C. R. and Brunei, D. The preparation and use of novel immobilised guanidine catalysts in base-catalysed epox-idation and condensation reactions, Green Chem., 2000, 2, 283-288. 

GUANIDINE CATALYSTS SUPPORTED ON SILICA AND MICELLE TEMPLATED SILICAS. NEW BASIC CATALYSTS FOR ORGANIC CHEMISTRY... 

Guanidine Catalysts Supported on Silica and Micelle Templated Silicas... 

Table 3 Conversion of heptanal to non-3-enoic acid using supported guanidine catalysts.

Novel supported guanidine catalysts, based on 1,1,3,3-tetramethylguanidine have been prepared using a variety of synthetic routes. The catalysts have been shown to be efficient catalysts for the base-catalysed epoxidation of electron-deficient alkenes, and show promise in the Linstead variation of the Knoevenagel condensation. 

There are reports that extend the nature of the catalyst beyond an oxazaborolidine framework. One such example made use of a chiral guanidine catalyst.11 Proline-derived 25 was converted to guanidine 26 in good yield. This species was capable of reducing ketones 27 to alcohols 28 by the addition of BH3-SMe2. 

With these results in hand, the Corey labs were able to utilize a readily available chiral C2-symmetical bifunctional guanidine catalyst 59.34 They rationalized the origin of the enantioselectivity to a pre-transition state assembly of the catalyst 59, the imine 60, and cyanide. Additionally, DFT modeling studies using the B3LYP method gave rise to two competitive pathways for the catalytic cycle.34b Concomitant hydrolysis of the nitrile and deprotection of the amine converted 61 to amino acids 62. 

P-lO - Guanidine catalysts supported on silica and micelle templated silicas new basic catalysts for organic chemistry... 

A C2-symmetrical pentacychc guanidinium salt like 16 (Figure 4.5) was used for the conjugate addition of pyrrolidine to y-crotonolactone, in which structural requirement such as the size of the cavities and substituents on tetrahydropyran rings of the guanidine catalysts is critical for asymmetric induction [23]. 

An axially chiral and highly hindered binaphthyl-derived guanidine catalyst 18a with an internal guanidine unit (Figure 4.6) facilitates the highly enantioselective 1,4-addition... 

A review elsewhere discusses catalytic Strecker reactions including guanidine catalysts [64]. 

Macquarrie, D.J., Modoe, J.E.G., Brunei, D. et a/. (2001) Guanidine catalysts supported on silica and micelle templated sihcas. New basic catalysts for organic chemistry. Royal Society of Chemistry, 266, 196-202. 

Jerome, R, Kharchafi, G., Adam, I. and Barrault, J. (2004) One pot and selective synthesis of monoglycerides over homogeneous and heterogeneous guanidine catalysts. Green Chemistry, 6, 72-74. 

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