Chiral carbene

Scheme 27 Rigid chiral carbene complex chelates in diastereoselective benzannulation...

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). 

Herrmann et al. reported for the first time in 1996 the use of chiral NHC complexes in asymmetric hydrosilylation [12]. An achiral version of this reaction with diaminocarbene rhodium complexes was previously reported by Lappert et al. in 1984 [40]. The Rh(I) complexes 53a-b were obtained in 71-79% yield by reaction of the free chiral carbene with 0.5 equiv of [Rh(cod)Cl]2 in THF (Scheme 30). The carbene was not isolated but generated in solution by deprotonation of the corresponding imidazolium salt by sodium hydride in liquid ammonia and THF at - 33 °C. The rhodium complexes 53 are stable in air both as a solid and in solution, and their thermal stability is also remarkable. The hydrosilylation of acetophenone in the presence of 1% mol of catalyst 53b gave almost quantitative conversions and optical inductions up to 32%. These complexes are active in hydrosilylation without an induction period even at low temperatures (- 34 °C). The optical induction is clearly temperature-dependent it decreases at higher temperatures. No significant solvent dependence could be observed. In spite of moderate ee values, this first report on asymmetric hydrosilylation demonstrated the advantage of such rhodium carbene complexes in terms of stability. No dissociation of the ligand was observed in the course of the reaction. 

The employment of silver(i) complexes having a chiral carbene ligand L (Figure 19) and the empirical formula [AgBrL] has been reported for use as both carbene-transfer reagents to the corresponding dichloropalladium(n)... 

Iridium complexes are known to be generally less active in hydrosilylation reactions when compared to rhodium derivatives, although iridium-based catalysts with bonded chiral carbene ligands have been used successfully in the synthesis of chiral alcohols and amines via hydrosilylation/protodesilylation of ketones [46-52] and imines [53-55], The iridium-catalyzed reaction of acetophenone derivatives with organosubstituted silanes often gives two products (Equation 14.3) ... 

Neutral iridium(I) complexes [Ir(Cl)(cod)(L)] [46] consisting of the chiral carbene ligands LI and L2 have been shown as active catalysts for the asymmetric hydrosi-... 

Ortho-directed metallations also allowed the synthesis of ferrocene-based hydroxamic acids such as 17 and 18 [23] as well as the preparation of planar-chiral carbenes 19 and 21 (which were trapped as chromium and rhodium complexes, 20 and 22, respectively) [24], In this context it is noteworthy that 19 was the first carbene with planar chirality ever reported. 

The prochiral aziridine 1 is easily prepared from cyclooctene. Paul Muller of the University of Geneva has shown (Helv. Chim. Acta 2004,87,227) that metalation of 1 in the presence of the chiral amine sparteine leads to the bicyclic amine 3 in 15% , by way of intramolecular C-H insertion by the intermediate chiral carbene 2. The sparteine can be recovered and recycled. 

Hartwig has reported the asymmetric intramolecular arylation of amides using a chiral carbene ligand (5) with up to 76% ee [43]. 

KR of an Aryl Alkyl sec-Alcohol Using Chiral Carbene Catalyst KR of (+)-l-Phenylethanol (Analytical Scale) [73] (p. 299)... 

To a solution of chiral carbene catalyst (0.03 mmol, 5 mol%) and 1-phenyletha-nol (73.2 mg, 72 pL, 0.6 mmol) in THF (2 mL) was added vinyl diphenylacetate (117.5 mg, 0.45 mmol) dropwise at —78 °C. The reaction mixture was stirred at this temperature for 3 h, and then treated with 0.1 M HCl and extracted with ether. The combined organic layers were washed with brine, dried (Na2S04), and concentrated in vacuo. The residue was purified by FC on silica gel (ether hex-anes, 1 50 to 1 2) to afford (P)-l-phenylethyl diphenylacetate (65 mg, 32%, 96% ee by chiral-HPLC) and (S)-l-phenylethanol (44.6 mg, 61%, 52% ee by chiral HPLC). The calculated selectivity value at 34% conversion was s = 80. 

Following this first publication by Bolm s group, Togni et al. reported the synthesis of the C2-symmetric chiral carbene ligand 42 using Ugi s chiral 1-ferrocenylethylamine as starting material (Scheme 32) [88]. 

The chiral carbene 42 contains two types of chiral elements, planar chirality in the ferrocenyl units and chiral centers at the carbon atoms linking the ferrocene with the N-heterocycles. This combination is frequently found... 

The two chiral carbene ligands 22 and 23 are of interest, although the selec-tivities achieved were not high [24,25]. 

A typical reaction involves an in situ generated copper(l) catalyst with an NHC ligand and dialkylzinc [79-81] or EtMgBr [82] as the alkyl source (see Figure 2.10). A typical substrate is the prochiral cyclohexenone [83-85]. Chiral carbenes are therefore preferred and the introduction of an additional functionality (besides an element of chirality) on the carbene is not immediately obvious. 

Note The chiral carbene ligand in Figure 5.9 has its asymmetric centres far removed from the carbene carbon atom (five bonds). This yields a transition metal carbene complex with remote chirality that cannot be expected to efficiently transfer the chiral information to a prochiral substrate resulting in low chiral resolution (% ee) of the product. 

Figure 5.9 Synthesis of palladium(ll) and silver(l) carbene complexes using a chiral carbene ligand derived from 1,2-diaminocyclohexane.

Figure 5.11 A monodentate chiral carbene based on 1,2-diamlnocyclohexane.

A convenient method for chiral carbene complexes is provided by oxidative addition of a C-Cl bond of a suitable precursor to a transition metal centre like palladium(O) [50]. The method has of course limited scope, since not aU transition metals have appropriate precursor complexes in low oxidation states. 

So far, we have considered protocols that result in chiral centres in the C and position (actnally always with the same substiment). Let us now turn to satnrated carbenes that have only one chiral centre in the backbone. Figure 5.15 shows a procedure that utilises a chiral diamine derived from proline, a naturally occurring a-amino acid. Reaction with aniline to the corresponding amide and reduction with LiAlH yields the diamine used [60]. The actual synthesis of the chiral carbene then calls for reaction of the proUne derived diamine with thiophosgene and subsequent S/Cl exchange with oxalyl chloride [50]. The... 

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