Diamines, chiral sparteine

D. Reactions with the Chiral Diamine Ligand (—)-Sparteine... 928... 

The rate-determining step occurs during (3-hydride elimination. One model for enantioselection is shown in Figure 12-4, where the diamine ligand, (- sparteine, exhibits Q symmetry48 instead of C2. C2 symmetry is associated with dia-stereomeric structure 22b, (-)-a-isosparteine). C2 is also the inherent symmetry of chiral bisphosphine ligands used for asymmetric hydrogenation.49... 

In the majority of cases, the deprotonation of carbamates occurs in the presence of diamines (TMEDA, sparteine or like-sparteine diamine). Complex s-BuLi with the chiral (-)-sparteine efficiendy and enantioselectively deprotonates N-Boc-pyrrolidine (127), but the same base complex is less effective with N-Boc-piperidine. So, lithiation of N-t-Boc-piperidine with sec-BuLi-(-)/sparteine requires 16 h for completion of the deprotonation and after subsequent addition of trimethylchlorosilane, the yield of (S)-195 is detected to be only 8% (133). However, the replacement of sparteine by other diamine results in the increased yield of (S)-195 (135). 

In 2003, Sigman et al. reported the use of a chiral carbene ligand in conjunction with the chiral base (-)-sparteine in the palladium(II) catalyzed oxidative kinetic resolution of secondary alcohols [26]. The dimeric palladium complexes 51a-b used in this reaction were obtained in two steps from N,N -diaryl chiral imidazolinium salts derived from (S, S) or (R,R) diphenylethane diamine (Scheme 28). The carbenes were generated by deprotonation of the salts with t-BuOK in THF and reacted in situ with dimeric palladium al-lyl chloride. The intermediate NHC - Pd(allyl)Cl complexes 52 are air-stable and were isolated in 92-95% yield after silica gel chromatography. Two diaster corners in a ratio of approximately 2 1 are present in solution (CDCI3). 

Sparteine has been widely studied as a catalyst for asymmetric synthesis. Because only (—)-sparteine 10 is commercially available, there has been much interest in the development of (-l-)-sparteine mimics, among which the most important is diamine 467, which has been employed as a chiral reagent or catalyst in a large number of asymmetric synthesis procedures <2006S2233>. 

The C2 symmetric chiral diether 28" and the naturally occurring chiral diamine, (—)-sparteine (29), have been the most successful external chiral ligands for asymmetric conjugate addition of organolithium reagents. The rest of this review highlights organolithium addition, which is mediated or sometimes catalyzed by 28 or 29. 

A-Boc-A -isopropylimidazolidine (175) is deprotonated by the (—)-sparteine method and alkylated to form imidazolidines 176 (equation 41). The yields remain below 50%, since only a part of 175 exists in the shown conformation, which is required for the directed deprotonation. At low temperature, the interconversion between the s-trans- and i-c -conformation is too slow. Ring cleavage furnishes synthetically useful chiral 1,2-diamines 177. 

Nakajima and co-workers have carried out extensive investigations into the influence of different chiral diamine-copper complexes on the oxidative dimerization of naphthols [146-148]. As emerged from Smrcina s work, the inclusion of an ester moiety on the naphthol precursor is an important factor for optimizing the enantioselectivity. After establishing a catalytic cycle with TMDA as the base and showing that sparteine gave promising results (Scheme 57), they focused their work on other chiral diamines (Table 39) [147]. 

Katsuki and co-workers have investigated asymmetric epoxidation reactions mediated by achiral Mn(salen) complexes in the presence of chiral additives the combination of tetramethyl diamine-derived complex 37 and (—)-sparteine 38 can mediate the oxidation of chromenes with up to 73% ee (Table 2, entry 1) however, the yields were low <1997T9541>. More successful was ethylene diamine-derived complex 39, which promoted the asymmetric epoxidation of several chromenes in good to excellent yields and good levels of ee in combination with chiral... 

The addition of alkyllithiums to allylic alcohols, originally described by Felkin and Crandall [83], has recently acquired new interest due to the enantioselective approach of the carbometallation reaction of cinnamyl derivatives. Indeed, asymmetric carbolithiation of ( )-cinnamyI alcohol in hexane or cumene, in the presence of the readily available chiral diamine (—)sparteine, leads to the carbometallated product in 82% ee. Primary as well as secondary alkyllithiums lead to identical enantioselection [128] (Scheme 7-108). 

Studies suggest that the mechanism of AHRs is quite similar to the achiral version, which includes the same fundamental steps in the catalytic cycles that we have seen already. The major difference is the presence of chiral bidentate ligands, such as bisphosphines [R2P-Y-PR2], phosphine-phosphites [R2P-Y-P(OR)2], bisphospites [(RO)2P-Y-P(OR)2], aminophosphines [R2N-Y-PR2], or diamines (such as (-)-sparteine), which we encountered earlier in Chapter 12. The bidentate variation of the cationic cycle, shown in Scheme 12.15b, seems to explain most aspects of the mechanism of AHR when X = OTf or I (in the presence of halide scavengers). Throughout the cycle, the ligand remains bidentate, and this factor seems to enhance enantioselectivity. The neutral cycle variant, which ought to be... 

As yet the main class of chiral complexes with tetrahedral coordination investigated spectroscopically are the [MW(diamine)X2] series, where M is cobalt, nickel, ot copper X is a haUde or pseudohaUde anion and the diamine is chiral and di-tertiary, notably, (—)-spartein (II), and its epimers, (—)-a-isospartein (HI) and (+)-d-isospartein... 

Sparteine 2 is also an excellent chiral diamine hgand in stoichiometric amounts as shown by the hgand-directed conjugate addition of chirally fixed organolithium species. The choice of ligand for lithium can provide control of 1,2-vs 1,4-addition of organohthium species to a,P-unsatuxated carbonyl substrates... 

More recently, Hoppe has also compared (-)-sparteine 2 with (-)-a-iso-sparteine 28 and N,Ar,AT, Ar -tetramethyldiamine 4 in the enantioselective deprotonation of alkyl carbamates. It was found that a-isosparteine 28 does not support the deprotonation of alkyl carbamates at all, whereas 4 generally gave lower levels of ee (Scheme 13) compared with sparteine [42]. However, the slimmer hgand 4 facilitated enantioselective deprotonation of hindered carbamate 27 (R = t-Bu) in 79% ee, whereas (-)-sparteine 2 failed to effect deprotonation a delicate balance in the steric demand of the CH-acid (alkyl carbamate) and the inducing diamine therefore determines the success of the deprotonation. Quantum-chemical calculations (PM3, ab initio methods) on several models for the competing diastereomeric transition states of the deprotonation under the influence of 2 were found to reflect well the sense and the magnitude of the experimentally observed chiral induction. 

Although early studies by Nozaki examined (-)-sparteine 2 in the asymmetric lithiation of isopropylferrocene (as noted in Sect. 1.1 above), the first enantioselective generation of planar chirality in good ees using an organolithium (Clay-don, in this volume) was reported by Uemura in 1994 in the lithiation of tricar-bonyl(q -phenyl carbamate)chromium complexes using chiral diamines. After quenching with electrophiles, enantioenriched (o-substituted phenyl car-bamate)chromium complexes were obtained in up to 82% ee (Scheme 19) [61]. 

An alternative approach to the asymmetric synthesis of arenechromium tricarbonyls is to use achiral alkylHthiums in the presence of a chiral ligand - the diamine (-)-sparteine 85, for example. In a study of the relative efficiencies of a range of diamines, Uemura showed that the best Hgand for introducing enantio-selectivity into the hthiation of 158 and 161 was the diamine 159 (Scheme 42) [101]. (-)-Sparteine 85 performed relatively poorly with 158. 

Alkyllithiums can be turned into chiral bases in quite a simple way—by complexation with a chiral ligand. A widely used example is the tetracyclic diamine (-)-sparteine. Sparteine s structure looks complex, but it is a relatively widely available natural product which folds around the lithium atom of an alkylUthium and places the base in a chiral environment. 

Since Evans et al. [78] has discovered that prochiral alkyl(dimefliyl) phosphine boranes can undergo the enantioselective deprotonation of one methyl group, using butyllithium and ( )-sparteine 141, these compounds have been widely used for the synthesis of P-chirogenic borane phosphines [79-105]. Lithium alkyls form chiral complexes 142 with sparteine 141 and related chiral diamines, which were investigated by single crystal X-ray analysis (Scheme 43) [82-87]. 

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