Asymmetric reactions diazo compounds

Since their first introduction by Brunner and McKervey as chiral catalysts for the asymmetric cyclopropanation of alkenes with diazo compounds, chiral dirhodium tetra(A-arylsulfonylprolinates) complexes have been widely used by Davies,in particular, in the context of these reactions. Therefore, the use of... 

In 1966, Nozaki et al. reported that the decomposition of o-diazo-esters by a copper chiral Schiff base complex in the presence of olefins gave optically active cyclopropanes (Scheme 58).220 221 Following this seminal discovery, Aratani et al. commenced an extensive study of the chiral salicylaldimine ligand and developed highly enantioselective and industrially useful cyclopropanation.222-224 Since then, various complexes have been prepared and applied to asymmetric cyclo-propanation. In this section, however, only selected examples of cyclopropanations using diazo compounds are discussed. For a more detailed discussion of asymmetric cyclopropanation and related reactions, see reviews and books.17-21,225... 

Certain transition metal complexes catalyze the decomposition of diazo compounds. The metal-bonded carbene intermediates behave differently from the free species generated via photolysis or thermolysis of the corresponding carbene precursor. The first catalytic asymmetric cyclopropanation reaction was reported in 1966 when Nozaki et al.93 showed that the cyclopropane compound trans- 182 was obtained as the major product from the cyclopropanation of styrene with diazoacetate with an ee value of 6% (Scheme 5-56). This reaction was effected by a copper(II) complex 181 that bears a salicyladimine ligand. 

An important competing process with significant practical consequences is the catalytic dimerization of diazoacetate to form maleate and fumarate esters. Most catalysts suffer from this side reaction, leading to the use of the alkene as solvent in order to accelerate the productive pathway and the slow addition of diazo compound in order to minimize dimerization. Since this problem is generally shared across most catalyst architectures, it will be mentioned in discussions of individual asymmetric catalyst systems only in those instances where these precautions prove to be unnecessary. 

In summary, the chemistry of the donor/acceptor-substituted carbenoids represents a new avenue of research for metal-catalyzed decomposition of diazo compounds. The resulting carbenoids are more chemoselective than the conventional carbenoids, which allows reactions to be achieved that were previously inaccessible. The discovery of pan-tolactone as an effective chiral auxiliary, and rhodium prolinates as exceptional chiral catalysts for this class of rhodium-carbenoid intermediate, broadens the synthetic utility of this chemistry. The successful development of the asymmetric intermolecular C-H activation process underscores the potential of this class of carbenoids for organic synthesis. 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

Mark Elliott was born in Doncaster. He studied in Loughborough, where he obtained a BSc in 1991 and a PhD in 1994 working with Prof. C. J. Moody on transition-metal-catalyzed reactions of diazo compounds. After postdoctoral work with Prof A. Pfaltz, initially in Basel under the auspices of a Royal Society European Exchange Fellowship, and later at the Max-Planck Institute in Miilheim, he returned to the UK in 1996 to take up his current position as lecturer in chemistry at Cardiff His reseach interests include asymmetric heterocyclic chemistry, asymmetric catalysis, and natural product chemistry. 

The glyoxime-Co(II)-catalyzed asymmetric cyclopropanation shown in Scheme 94 is noteworthy (226). The results of the detailed kinetic study are consistent with the mechanism of Scheme 92, however, the intermediary Co carbenoid species has substantial radicaloid properties, and only styrene and other conjugated olefins can be used as substrates. Simple alkenes are not cyclopropanated by diazo compounds. The reaction of deuterated styrene proceeds in non-stereospecific manner without retention of geometrical integrity. 

The range of alkenes that may be used as substrates in these reactions is vast Suitable catalysts may be chosen to permit use of ordinary alkenes, electron deficient alkenes such as a,(3-unsaturated carbonyl compounds, and very electron rich alkenes such as enol ethers. These reactions are generally stereospecific, and they often exhibit syn stereoselectivity, as was also mentioned for the photochemical reactions earlier. Several optically active catalysts and several types of chiral auxiliaries contained in either the al-kene substrates or the diazo compounds have been studied in asymmetric cyclopropanation reactions, but diazocarbonyl compounds, rather than simple diazoalkanes, have been used in most of these studies. When more than one possible site of cyclopropanation exists, reactions of less highly substituted alkenes are often seen, whereas the photochemical reactions often occur predominantly at more highly substituted double bonds. However, the regioselectivity of the metal-catalyzed reactions can be very dependent upon the particular catalyst chosen for the reaction. 

A vast array of chiral catalysts have been developed for the enantioselective reactions of diazo compounds but the majority has been applied to asymmetric cyclopropanations of alkyl diazoacetates [2]. Prominent catalysts for asymmetric intermolecular C-H insertions are the dirhodium tetraprolinate catalysts, Rh2(S-TBSP)4 (la) and Rh2(S-DOSP)4 (lb), and the bridged analogue Rh2(S-biDOSP)2 (2) [7] (Fig. 1). A related prolinate catalyst is the amide 3 [8]. Another catalyst that has been occasionally used in intermolecular C-H activations is Rh2(S-MEPY)4 (4) [9], The most notable catalysts that have been used in enantioselective ylide transformations are the valine derivative, Rh2(S-BPTV)4 (5) [10], and the binaphthylphosphate catalysts, Rh2(R-BNP)4 (6a) and Rh2(R-DDNP)4 (6b) [11]. All of the catalysts tend to be very active in the decomposition of diazo compounds and generally, carbenoid reactions are conducted with 1 mol % or less of catalyst loading [1-3]. 

Rh(II) carboxylates, especially Rh2(OAc)4> have emerged as the most generally effective catalysts for metal carbene transformations [7-10] and thus interest continues in the design and development of dirhodium(II) complexes that possess chiral51igands. They are structurally well-defined, with D2h symmetry [51] and axial coordination sites at which carbene formation occurs in reactions with diazo compounds. With chiral dirhodium(II) carboxylates the asymmetric center is located relatively far from the carbene center in the metal carbene intermediate. The first of these to be reported with applications to cyclopropanation reactions was developed by Brunner [52], who prepared 13 chiral dirhodium(II) tetrakis(car-boxylate) derivatives (16) from enantiomerically pure carboxylic acids RlR2R3CC OOH with substituents that were varied from H, Me, and Ph to OH, NHAc, and CF3. However, reactions performed between ethyl diazoacetate and styrene yielded cyclopropane products whose enantiopurities were less than 12% ee, a situation analogous to that encountered by Nozaki [2] in the first applications of chiral Schiff base-Cu(II) catalysts. 

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 required chiral sulfur ylide of type 59 is formed in a reaction with a diazo compound in the presence of an achiral metal catalyst. Subsequently, asymmetric reaction of the chiral ylide 59 with the C=N double bond of the imine proceeds diastereoselectively and enantioselectively, giving the optically active aziridine 57. The chiral sulfide catalyst released is then used for the next catalytic cycle. The cat-alytically active species in the asymmetric process is the sulfide, so this concept can also be regarded as an organocatalytic reaction. 

Intermolecular insertion to aryl C—H bonds is possible. The asymmetric intramolecular reaction of the a-diazo compound 354 catalysed by Rh2[(S)-PTTL]4, Rh2[(S)—PTTL]4 = dirhodium tetrakis[N-phthaloyl(S)—t—leucinate], afforded indane... 

Nozaki, H., Takaya, H., Moriuti, S. and Noyori, R. (1968) Homogeneous catalysis in the decomposition of diazo compounds by copper chelates. Asymmetric carbenoid reactions. Tetrahedron, 24, 3655. 

Reaction of a ruthenium carbenoid species, formed from a diazo compound, with an alkene produces cyclopropanes. A variety of ruthenium catalysts, notably chiral catalysts, have been developed to lead to efficient asymmetric cyclopropanation of alkenes as in the following example [105] (Eq. 81). 

Incidentally, cyclopropanation, one of the carbon-carbon bond formation reactions, is a useful reaction by using diazo compounds to give a variety of keto or alkoxycarbonyl cyclopropane derivatives, for example, crythantimates and their analogues as popular insectsides [2]. The cyclopropanation reactions have often been carried out with the use of copper or rhodium catalysts however, this results in stereochemical problems of trans-cis selectivity or asymmetric induction [3]. 

The control of carbene reactions from diazo compounds as precursors is classically mediated by copper catalysts and all the carbene reactions discussed in Section 8 are, in fact, improved by such catalysts. Moreover, the use of ligands on the metal allows some control of the stereochemistry of the products, the most striking example being the asymmetric synthesis of cyclopropanes with an excellent optical yield (>90S ce) [35]. 

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