Asymmetric carbenes

In addition, a proline- or phenylalanine-based Rh(II) can catalyze intramolecular asymmetric carbene reactions such as aromatic ring expansion and C—H insertion with moderate selectivity (Scheme 95) (229). Rh(II) carboxamides are also effective catalysts for asymmetric C—H or N—H insertion (228c). 

With respect to the application of asymmetric carbene catalysis as a tool for enantioselective synthesis, the last decade s major success is based on substantial improvements in catalyst development. Early reports dealt with implementing chirality in thiazolium scaffolds (Sheehan and Hunneman 1966 Sheehan and Hara 1974 Dvorak and Rawal 1998), but their catalytic performance suffered from either low yields or low ee-values. In this regard, the investigation of triazole heterocycles as an alternative core structure (Enders et al. 1995) has played a crucial role to provide heterazolium precatalysts improving both asymmetric benzoin and Stetter reactions. An intramolecular Stetter reaction yielding chromanones upon cyclization of salicylaldehyde-derived substrates is commonly used as a benchmark reaction to compare catalyst efficiency (Scheme 1 Ciganek 1995 Enders et al. 1996 Kerr et al. 2002 Kerr and Rovis 2004). 

Note Phosphanes can have an asymmetric phosphorus atom, but can NHC have an asymmetric carbene centre ... 

Dinuclear Rh complexes modified with optically active BNPPA catalyze asymmetric carbene reactions with moderate enantiose-lectivity (eq 3 and eq 4). ... 

It is possible to exactly identify and characterize the radical species and chain structures of the reaction intermediates, which are determined by their different reactive or unreactive chain ends. The reactive intermediates are best described by diradical (DR), asymmetric carbene (AC) and dicarbene (DC) oligomer molecules of different lengths. The respective singlet (S = 0), triplet (S = I) or quintet (S = 1) states and their roles in the polymerization process are investigated in detail by solid state spectroscopy. A one-dimensional electron gas model is successfully applied to the optical absorption series of the DR and AC intermediates as well as on the different stable oligomer SO molecules obtained after final chain termination reactions. 

From spectroscopic data, presented in the following, we conclude that the mechanism of polymerization is described by three series of intermediate states differing by the number of reactive radical or carbene chain ends these are the diradicals DR , the dicarbenes DC , and the asymmetric carbenes AC . Via a final chain termination reaction an additional series of reaction products is obtained. These are the stable oligomers SO with two unreactive chain ends. The schematic structures of the DR, DC, AC, and SO molecules are shown by example of the trimer in Table 2. The lengths of the dimer-, trimer-, tetramer-... units are characterized by the numbers n = 2, 3,4,... of the respective monomer molecules. The symbols and the schematic structures as well as the notation of the optical and the ESR absorption lines, are summarized in Table 2. 

The absorption lines of the low temperature photoreaction products in TS-6 monomer crystals are summarized in the diagram of Fig. 7. The correlation of the A, B, C,. .. photoproduct series to diradical DR intermediates and of the b, c, d,... photoproducts to asymmetric carbene AC intermediates is based on the ESR experiments discussed below. The correlation of the y, 8,6,... series to stable oligomers SO is based on their thermal and optical stability. The correlation of dimer, trimer, tetramer,... molecules follows from the chemical reaction sequences observed in the time resolved optical and ESR measurements as well as from the widths of the one-dimensional potential wells used in the simple electron gas theory , which already has proved successful in its application to dye molecules. Following Exarhos et al. the explicit dependence is given by... 

Fig. 12. High field part of the triplet ESR spectrum of the asymmetric carbenes. Only the high field partners of the pair lines have been assigned by the numbers...

Fig. 13. Formation of the asymmetric carbenes upon UV-irradiation, The calculated dependencies have been fitted to the experimental points...

Fig. 14. Transformation of the diradical ESR line 1 to the asymmetric carbene ESR line 2 upon resonant irradiation into the photoproduct A absorption. The concentration of the triplet species has been deduced from the evaluation of the ESR spectra...

The individual chain ends of the DC intermediates exhibit the same mesomeric structures (4) of the corresponding asymmetric carbenes AC and a carbon backbone with acetylene structure. It has been shown in a quantitative theory of the DC quintet states that the fine structure parameters Dq of all DC intermediates are... 

The photoinitiation reaction (phi) is defined by the reaction Eq. (9). The dimer generation rates G2 of the diradical and asymmetric carbene dimer molecules are therefore given by the bimolecular rate equations... 

As we have seen above there are certain probabilities x in all low temperature photoaddition reaction steps that the first termination reaction will occur, i.e. the transformation of the diradical intermediates to the asymmetric carbene intermediates (DR -+AC +i). The second termination reactions, in which finally the stable oligomers are produced from the AC intermediates (AC -+ SO +i) may be characterized by the probabilities y . Therefore, a simplified reaction scheme is given by ... 

This asymmetric carbene reaction has been extended successfully, but in an unexpected direction [37]. Thus, as illustrated in Scheme 10, the cyclopropane synthesis is now used for the industrial synthesis of Cilastatin (36), which acts as an excellent in vivo stabilizer of the antibiotic Imipenem (37) (Merck Co., USA, and Sumitomo Chemical Co. Ltd., Japan). Chiral bisoxazolidine-Cu complexes (Structures 38 and 39) also exhibit high efficiency in asymmetric cyclopropanation [38]. 

Photolyses of l-azi-2-methylcyclohexane (26) were performed within a-, /)- and y-CyDs to alter the selectivity of the carbene intermediate, 2-methylcyclohexanylidene (27). It was hypothesized that constriction of asymmetric carbene 27 within the CyD hosts would suppress the formation of 1-methylcyclohexene (28) and concomitantly enhance that of 3-methylcyclohexene (29) and bicyclo[4.1.0]heptane (30). However, no 30 was observed. 

The asymmetric carbene transfer is governed by the chirality at iron, while the chiral phosphine ligand, required for resolution of the complexes, is of negligible influence. A broad mechanistic discussion has been presented83. 

Ru=CH-, <5h=21.7 ppm (s), <5 =305.7 ppm (7c-h= 142.4 Hz) [57]. Complex24released only trans-phenylcyclopropanecarboxylate at 60 °C by tbe reaction with styrene in 82% yield and 97% ee. Moreover, complex 24 acted as a catalyst in tbe same way as tbe etbylene complex 8 at 50 °C, 95% yield, 98 2 trans-to-cis ratio with 93% ee for tbe trans form. Thus, tbe mechanism of AGP catalyzed by Ru Pybox was explained by isolation of tbe corresponding carbene complexes and realization of tbe asymmetric carbene transfer reaction. 

More recently, chiral Ru-porphyrin polymers were used for catalytic asymmetric carbene transfer. A C2-symmetric group containing two norbomane moieties fused to the central vinyl substituted benzene ring of a porphyrin was chosen in order to induce the chirality. Then the chiral ruthenium vinylporphyrin 101 was involved into radical copolymerization with styrene and DVB or EGDMA to lead respectively to monolithic resins chiral 102 and 103 which were crushed (Scheme 48). 

Polarized optical absorption spectra of the diradical (DR), the asymmetric carbene (AC) and the stable oligomer (SO) molecules. The dimer (n=2) spectra (A,a,ot) are given by the upper part. The spectra with n > 2 are shown in the lower part. 

All ESR lines show partially resolved hyperfine structure as shown in Figure 8, due to hyperfine interaction of the electron spin with the nuclear spins = I2 = 1/2 of the two protons of the CH2-rest group. In the case of the diradicals and dicarbenes two CH2 groups of the two chain ends are involved in the hyperfine interaction. In the case of the asymmetric carbenes only one chain... 

Fig. 13 Absorption energy of diradicals (DR), asymmetric carbenes (AC) and stable oligomers (SO) as a function of chun length in partially polymerized PDA-TS.

Ferrand Y, Le Maux P, Simonneaux G (2005) Macroporous chiral mthenium porphyrin polymers a new solid-phase material used as a device for catalytic asymmetric carbene transfer. Tetrahedron Asymmetry 16 3829-3836... 

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