Carbenes asymmetric reactions

Enantiomerically pure copper and rhodium complexes enable enantioselective catalysis of carbene-mediated reactions. Such reactions will be discussed more thoroughly in Section 4.2. Experimental Procedure 4.1.1 describes the preparation of an enantiomerically pure rhodium(II) complex which has proven efficient for catalysis of different types of carbene complex-mediated C-C-bond-forming reactions with high asymmetric induction. 

Transfer of a metal carbene moiety from a metal carbene complex to a heteroatom other than oxygen, sulfur, and nitrogen is possible. One such example is the report by Uemura and co-workers, who disclosed catalytic asymmetric reaction of ethyl diazoacetate with ( )-cinnamyl phenyl selenide 193 (Equation (30))." The reaction afforded 194 as a diastereomeric mixture (58 42). Using Rh2(5[Pg.173]

Intramolecular cyclopropanation reactions of alkenyl diazo carbonyl compounds are among the most useful catalytic metal carbene transformations, and the diversity of their applications for organic syntheses is substantial [7,10,24,84]. Their catalytic asymmetric reactions, however, have only recently been reported. An early application of the Aratani catalyst 2 (A = PhCH2) to... 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

Of the numerous examples of asymmetric reactions catalyzed by Lewis bases, this chapter focuses mainly on the activation of silicon reagents and related processes. Various other types of Lewis basic (nucleophilic) activation, namely the Morita-Baylis-Hillman (MBH) reaction, acyl transfer, nucleophilic carbenes, and carbonyl reduction, are described in the other chapters of this book. 

All the examples described above involved the reaction of diazoacetate derivatives with silver salts to initiate the formation of a putative silver carbene however, other pathways exist. For example, Porcel and Echavarren have reported an intramolecular cyclization of an allylstannane to a pendent alkyne (Scheme 8.22) that involves the intermediacy of a silver carbene.52 As can be seen in Table 8.12, the reactions proceeded in moderate to excellent yield, providing the dienylstannane, while in some cases, reductive destannylation occurred. Several asymmetric reactions were reported with substrate ( )-145d, leading to the formation of the expected adduct in reasonable enantioselectivities (ee = 73-78%) in a preliminary screen with a number of different ligands. 

The combination of axial and central chirality in ligands of type 7 does not notably increase the asymmetric induction during coppcr-catalyzed carbene transfer reactions. Phenylethene and ethyl diazoacetatc provide the corresponding cyclopropane with at best 75% ee85. 

The ability of rhodium or copper complexes to promote carbene formation allows the study of asymmetric reactions with chiral ligands attached to the metal centre. Some highly enantioselective transformations are possible in certain cases. For example, the lactone 101 was formed with high optical purity using the complex [Rh2(5S-MEPY)4] (4.79). In the absence of competing intramolecular reactions, intermolecular C—H insertion is possible and such reactions are also amenable to asymmetric induction. Thus, high enantioselectivity in the insertion into a C—H bond of cyclohexane has been reported (4.80). 

By stereoselective additions of carbenes or carbene equivalents to alkenes optically pure cyclopropanes are obtained. " In concerted [2+1] cycloadditions the stereochemistry of the alkene is conserved in the products. (Z)-configurated alkenes lead stereospecifically to cis-cyclopropanes. So far, compared to [2+1] cycloadditions involving alkenes bearing the chiral auxiliary, asymmetric reactions involving chiral carbene precursors proved to be less efficient. 

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. 

Attempts to carry out carbene transfer reactions with chiral palladium catalysts were unsuccessful so far. Demnark et al. conducted a detailed study in which cyclopropana-tions of a,/3-unsaturated carbonyl compounds with diazomethane catalyzed by bis-(oxazoline)palladium(n) complexes were investigated. Virtual no asymmetric induction was obtained in these reactions which led to the conclusion—especially in light of the excellent asymmetric enviromnent bis(oxazolines) metal complexes offer in general—-that partial or complete ligand dissociation must have been occurred during the course of the reaction. 

Rh-catalyzed asymmetric C—H bond functionalization via a carbene insertion reaction was extensively documented in the early days, especially the intramolecular reactions. Thanks to enormous efforts from the groups of Davies and Doyle, asymmetric intramolecular C—H bond insertion by Rh carbenoids has become a reliable methodology and has been employed frequently in the total synthesis of complex natural products. " " ... 

At first glace, it would appear odd that a reaction that principally involves the manipulation of sp -hybridized carbon atoms should lend itself to a useful asymmetric version. If the initially generated carbene is, however, offered the choice of two enantiotopic alkenes, then a useful asymmetric reaction can be contemplated (Scheme 8.103). Either enantiomer of the product can be formed depending on which of the two enantiotopic alkenes is selected. Significant modification of the metathesis catalyst with incorporation of chirality can be needed to achieve this aim. 

Triphase catalysts were also used for C-alkylations (Komeili-Zadeh, 1978) and have been shown to promote asymmetric addition in carbene addition reactions (Chiellini and Solaro, 1977 Colonna et al., 1978). Ammonium groups have been replaced by phosphoric triamides (Tomoi et al., 1978), phosphonium groups (Tundo, 1978), and polyethylene glycol (Regen and Dulak, 1977) to provide alternate phase-transfer agents. 

Synthesis of the chiral catalysts to introduce enantioselectivity in carbene transfer reactions is a subject of great interest. Often copper and rhodium chiral catalysts are of choice for the carbene transfer reactions. In some reports, immobilized chiral dirhodium (II) catalyst were employed successfully in asymmetric cyclopropanation reactions. Ubeda and coworkers reported the immobilization of chiral Rh2(02CR)2(PC)2 (PC = ort/io-metalated phosphine) compounds on cross-linked polystyrene (PS) resin by an... 

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

In 20 years of usage, a,/J-unsaturated Fischer carbene complexes demonstrated their multitalented versatility in organic synthesis, yet new reaction types are still being discovered every year. In view of their facile preparation and multifold reactivity, their versatile chemistry will undoubtedly be further developed and applied in years to come. The application of chirally modified Fischer carbene complexes in asymmetric synthesis has only begun, and it will probably be an important area of research in the near future. 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

The Diels-Alder reaction of simple alkoxy alkenylcarbene complexes leads to mixtures of endo and exo cycloadducts, with the endo isomer generally being the major one [96,97]. Asymmetric examples of endo Diels-Alder reactions have also been reported by the use of chiral auxiliaries both on the carbene complex and the diene. Thus, the reaction of cyclopentadiene with chiral alkenylcarbene complexes derived from (-)-menthol proceeds to afford a 4 1... 

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