backbone (Ar) and that attached on the guanidine nitrogen (G) had a strong impact on the stereoselectivity of the reactions. Chiral guanidine 29a was also utilized in the enantioselective direct vinylogous aldol reaction of furanones, as well as vinylogous Michael addition of furanones to nitroalkenes, to provide the corresponding adducts in high yields with high enantioselectivities (Scheme 3.43) [78].
Scheme 3.43. Enantioselective reactions of furanones as a pronucleophile catalyzed by 29a.
Source: [78].
On the other hand, the catalytic activity of seven‐membered 30 was confirmed by the highly enantioselective amination of β‐dicarbonyl compounds with azodicarboxylate (Scheme 3.44) [79]. In this catalyst design, the reach of the steric demand exerted by the aromatic substituents (Ar) is important to provide an efficient chiral environment around the substrate recognition site at the guanidine moiety. Therefore, the employment of chiral guanidine 30a with para‐biphenyl substituents having a bulky tert‐butyl groups at the 3,5‐positions of the terminal phenyl ring was essential to achieve the high level of stereocontrol. This type of chiral guanidine catalyst was also utilized in the enantioselective [3+2] cycloaddition of glycine imines with maleate [80].
Scheme 3.44. Enantioselective amination of β‐dicarbonyl compounds with azodicarboxylate catalyzed by 30a.
Source: Based on [79].
3.4. OTHER CHIRAL UNCHARGED ORGANOBASE CATALYSTS: CHIRAL ORGANOSUPERBASES
As described in the previous section, chiral bifunctional tertiary amine catalysts have been recognized as a particular class of chiral Brønsted base catalysts and have found a vast number of applications. However, the chiral tertiary amine catalysis still possesses inherent critical limitations; high catalyst loadings and long reaction times are often required, and arguably the range of pronucleophiles and electrophiles that are applicable to the reactions is rather narrow, which stem from the low basicity of tertiary amines. Only highly acidic compounds are applicable as pronucleophiles, and thus the resulting anionic nucleophiles only possess moderate nucleophilicity to react with highly electrophilic compounds. In this context, chiral uncharged organobases having higher basicity than chiral tertiary amines have attracted increased attention. This class of chiral organobases, including conventional chiral guanidines, is often called “chiral organosuperbase” although the definition of the term “organosuperbase” is rather ambiguous [1b]. The application of chiral organosuperbases has significant advantages. Most importantly, the chiral organosuperbases potentially broaden the scope of pronucleophiles to compounds having higher pK a values. In addition, the chiral organosuperbases increase the concentration of anionic nucleophiles. Consequently, they can dramatically accelerate the bimolecular reactions and decrease the catalyst loading and reaction time. Over the last decade, some new types of chiral organosuperbase catalysts have been developed, which is overviewed in this section.
3.4.1. Chiral Cyclopropenimine Catalysts
In 2012, Lambert and Bandar introduced chiral cyclopropenimines as a powerful class of chiral organobase catalysts for the first time (Figure 3.10) [81].
The basicity of 31 was measured and found to be higher than that of guanidines and comparable to that of P1‐phosphazenes. Their high basicity is attributed to the stabilization of the conjugate acid by three nitrogen lone pairs and an aromatic cyclopropenium ion. The superior catalytic activity of 31 was demonstrated in the enantioselective additions of glycine imines to various kinds of Michael acceptors and imines (Scheme 3.45) [82].
The mechanistic rationale was provided based on the experimental results along with computational study (Figure 3.11) [83]. The lowest‐energy enantiodetermining transition state involves the (E)‐enolate hydrogen‐bonded to the N‐H function of the protonated catalyst, with the acrylate hydrogen‐bonded to the catalyst hydroxy group. Interestingly, an unusual intramolecular C‐H… O interaction between a hydroxy group and a cyclohexane ring was identified as a key element in transition‐state organization.
Figure 3.10. Chiral cyclopropenimine catalyst.
Scheme 3.45. Enantioselective additions of glycine imines catalyzed by 31.
Source: Based on [82]. Source: Based on [81] and [82].
Figure 3.11. Mechanistic rationale.
Source: [83].
Jørgensen and co‐workers developed the enantioselective [3+2] cycloaddition of glycine imines with 2‐acyl cycloheptatrienes by using 31 (Scheme 3.46) [84]. 31 was also utilized in the catalytic enantioselective [2,3]‐Wittig rearrangement [85].
Scheme 3.46. Enantioselective [3+2] cycloaddition of glycine imines with 2‐acyl cycloheptatrienes catalyzed by 31.
Source: Based on [84].
3.4.2. Chiral Triaryliminophosphorane Catalysts
Dixon and co‐workers designed and developed a series of chiral bifunctional iminophosphorane (BIMP) catalysts 32 based on their idea of the introduction of an enhanced organobase functionality relative to tertiary amines into chiral acid–base bifunctional catalysts (Figure 3.12) [86].