Axial chiral backbones

Figure 5.22 Synthesis of a carbene precursor with an axially chiral backbone.

Figure 5.26 Synthesis of a carbene precursor with an axially chiral backbone made from ben-zannulated 1,1 -bipiperidine and its rhodium(l) complexes.

The numerous chiral phosphine ligands which are available to date [21] can be subclassified into three major categories depending on the location of the chiral center ligands presenting axial chirality (e.g., BINAP 1 and MOP 2), those bearing a chiral carbon-backbone (e.g., DIOP 3, DuPHOS 4), and those bearing the chiral center at the phosphorus atom (e. g., DIPAMP 5, BisP 6), as depicted in Fig. 1. 

In 2004, Shi et al. reported Pd-catalysed asymmetric allylic substitutions using axially chiral S/S- and S/O-heterodonor ligands based on the binaphthalene backbone. The test reaction was performed in the presence of... 

Concurrent with studies on cyclometalation, studies on the effects of the structure of phosphoramidite ligand had been conducted. Several groups studied the effect of the stmcmre of ligand on the rate and selectivity of these iridium-catalyzed allylic substitutions. LI contains three separate chiral components - the two phenethyl moieties on the amine as well as the axially chiral BINOL backbone. These portions of the catalyst structure can control reaction rates by affecting the rate of cyclometalation, by inhibiting catalyst decomposition, or by forming a complex that reacts faster in the mmover-limiting step(s) of the catalytic cycle. 

In 2004 and 2005, respectively, Bach and Miller independently described the use of chiral thiazolium salts as pre-catalysts for the enantioselective intramolecular Stetter reaction. Bach and co-workers employed an axially chiral A-arylthiazolium salt 109 to obtain chromanone 73 in 75% yield and 50% ee (Scheme 16) [77]. Miller and co-workers found that thiazolium salts embedded in a peptide backbone 65 could impart modest enantioselectivity on the intramolecular Stetter reaction [78]. In 2006, Tomioka reported a C -symmetric imidazolinylidene 112 that is also effective in the aliphatic Stetter reaction, providing three examples in moderate enantioselectivities (Scheme 17) [79]. 

Connon and co-workers synthesized a small library of novel axially chiral binaphthyl-derived bis(thio)ureas 152-165 and elucidated the influence of the steric and electronic characteristics of both the chiral backbone and the achiral N-aryl(alkyl) substituents on catalyst efficiency and stereodifferentiation in the FC type additions of indole and N-methylindole to nitroalkenes (Figure 6.50) [315]. 

Bach and co-workers developed the axially chiral N-arylthiazolium catalyst 41 bearing a menthol-derived backbone (Fig. 9.6) [45]. Using 20 mol% of this catalyst, they were able to isolate the Stetter product 30 (R = Me) in 75% yield with 50% ee. The low stereoselectivity was ascribed to an atropo-isomerization of the catalyst during the course of the reaction. 

In order to modulate the rotational and inversion processes associated with BIPHOS, the related P-NPr 2-functionalized 2,2 -biphospholes 103 a and 103 b have been prepared from the corresponding aminophospoles 102 a and 102 b, albeit it in low yield, ca. 10% (Scheme 123) <2002EJ0675>. In order to lock the axial chirality of the biphosphole, it proved crucial to have both the P-NPr 2 and phenyl groups on the ring backbone. Unlike compound 103 a, 103 b exists as two stable diastereoisomers. 

As we have seen in Chapter 1, it is very difficult to introduce chirality in the inamedi-ate vicinity of the carbene centre [23,24,46], An elegant way to circumnavigate this is to introduce a functional group on the carbene that can act as the carrier of chirality in the metal complex (see Figure 2.6). Excellent examples are a Cp scaffold for planar chiraUty [47 9] or the binaphthyl group for axial chirahty [50-52], The tether itself can be used as the chiral backbone as is the case in functionalised carbenes derived from 1,2-diamino cyclohexane [53,54],... 

A third example comes from Clyne et al. [358] and concerns the axial chiral binaphthyl backbone [359,360], itself known from phosphorus chemistry [361]. The synthesis starts from the trifluoromethylsulfonato substituted binaphthyl with a Kumada coupling reaction [291,292] with methytmagnesiumbromide. Oxidation with NBS yields the methyl brominated derivative that can be attached to the imidazole ring. Subsequent methylation results in the bis-imidazolium salt that is deprotonated to the bis-carbene and coordinated to the transition metal halide (Pd, Ni), a rather straightforward reaction sequence (see Figure 3.113). The overall yield for the four-step reaction to the bis-imidazolium salt is surprisingly good (65%). 

It is not strictly necessary to introduce the 1,1 -binaphthyl backbone. For axial chirality, the biphenyl scaffold is sufficient, provided that rotation around the phenyl-phenyl axis is sufficiently hindered. Hoveyda combined this reduced axial chiral motif with additional central chirality in the imidazole backbone (O and C ) [6,7], Synthetically, the task is accomplished by Buchwald-Hartwig amination of enantiomerically pure (H ,21 )-diphenylethylenediamine with 1-methoxy-I -iodo-biphenyl and subsequent reaction with mesityl bromide to introduce the bulky wingtip group on the second amino group of the chiral starting material. Ring closure reaction with triethyl orthoformate and hydrolysis of... 

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