Imines organocatalytic reduction

An alternative method for the organocatalytic reduction of imines employs Bronsted acids as catalysts and Hantzsch dihydropyridine as a reducing reagent. This topic is described in Chapter 11 (on Bronsted acids) [86]. 

Based on the above activation mechanism we wondered whether it would be possible to develop a biomimetic, organocatalytic reductive amination or transfer hydrogenation of ketimines. We reasoned that the activation of the imine by catalytic protonation through the Brpnsted acid should enable the hydrogen transfer from a suitable NADH mimic to yield the corresponding amine (Fig. 2). Hence, initial experiments focused on the examination of various Brpnsted acids in combination with different hydride sources (Rueping et al. 2005a). 

Soon afterward, MacMillan s group properly explored this organocatalytic reductive amination, observing that the ortho-triphenylsilyl phosphoric acid 17n in the presence of 5-A MS facilitates the desired coupling of acetophenone and 4-OMe-aniline in high conversion and with excellent levels of enantiocontrol at 40 C (87% yield, 94% ee) [55]. Authors report also the reduction of the pyruvic acid-derived cyclic imino ester with excellent enantioselectivity. However, implementation of the corresponding ethyl-substituted imine resulted in a dramatic decrease in... 

Although natural amino acids are readily available, there is a continuing need for unnatural amino acids. Jon C. AntiUa of the University of South Florida has described J. Am. Chem. Soc. 2007,129, 5830) a promising approach, based on the enantioselective organocatalytic reduction of imines such as 1 derived from a-keto esters. The aryl group is easily removed to give the primary amine. 

Rueping M, Sugiono E, Azap C, Theissmann T, Bolte M. Enantioselective Brpnsted acid catalyzed transfer hydrogenation organocatalytic reduction of imines. Org. Lett. 2005 7 3781-3783. 

Organocatalytic Enantioselective Reduction of Olefins, Ketones, and Imines... 

The organocatalytic enantioselective reduction of C=C, C=0, and C=N double bonds is a relatively young area for which many new and exciting developments can be expected in the near future. Hantzsch esters are useful organic hydrides, and a recent review has summarized the results obtained to date in organocataly-sis [27]. The case of silicon hydrides is convenient for imine or ketone reductions, as a chiral base can act as an organic catalyst. The asymmetric reductions of ketones catalyzed by oxazaborolidines and pioneered by Itsuno [28] and Corey [29] could not be included in this chapter. 

Using their earlier developed organocatalytic methods for imine reduction, they... 

In 2006, Enders and Vrettou [32] reported a concise total synthesis of (-l-)-poly-oxamic acid (82) through an organocatalytic Mannich reaction (Scheme 17.12). Asymmetric Mannich reaction of ketone 79 and Boc-protected imine 80 using L-proline 24 afforded the adduct 81 in 85% yield as a mixture of diastereomers with 92% ee (>98 2 dr). A stereoselective reduction of 81 using L-selectride, followed by ozonolysis and subsequent acid deprotection completed the total synthesis of (-l-)-polyoxamic acid (82). 

Since these seminal organocatalytic reports, other groups have used the same strategy for the reduction of different interesting imine derivatives such as MacMillan [62] [It is important to remark that as declared by the authors, the complete details of MacMillan s group concerning reductive amination were first... 

While most successful asymmetric organocatalytic imine reduction methodologies are limited to N-aryl imines. Sun et al. reported in 2008 that a new chiral sulfinamide catalyst 90 derived from L-proline is highly efficient for the reduction... 

Borane is one of the most common agents for reducing C=0 and C=N bonds and its applications for the enantioselective reduction of ketones and imines have been extensively studied in past decades [77]. Among such agents, the Corey-Bakshi-Shibata (CBS) catalyst, a chiral oxazaborolidine complex, which was discovered by Itsuno in 1981 [78] and further developed by Corey in 1987 [79], was widely considered as the most successful catalytic system. Several excellent reviews are already available [77a, 80]. In this chapter, we only give limited coverage of the organocatalytic asymmetric reduction of ketones by catalytic systems other than chiral oxazaborolidines. 

Chiral alcohols, respectively hydroxy groups, are a common motive in natural products and bioactive compounds. Therefore, the asymmetric reduction of ketones is a frequently used procedure. In contrast to the asymmetric reduction of imines vide infra), only few organocatalytic methods to reduce ketones are known, and mostly transition metal catalysis or enzymatic methods are used. The... 

The organocatalytic activation of electrophiles through (double) hydrogen bonding has been exploited in the transfer hydrogenation of imines and nitroolefins using Hanztsch esters. Unsubstituted thiourea was reported as efficient catalyst for the one-pot reductive animation of both aldehydes [77] and ketones [78] with various... 

---