Rhodium -mediated

The rhodium-mediated reaction of 69 with 2,3-dihydrofuran (a formal dipolar cycloaddition of a cyclic diazo dicarbonyl compound with a vinyl ether) yields 70. Corrqiound 70 can be transformed in a number of steps to 71 a,b <96TL2391>. 

In recent years, much attention has been focused on rhodium-mediated carbenoid reactions. One goal has been to understand how the rhodium ligands control reactivity and selectivity, especially in cases in which both addition and insertion reactions are possible. These catalysts contain Rh—Rh bonds but function by mechanisms similar to other transition metal catalysts. 

A mechanism involving Ir(m) and Ir(v) has been proposed (Scheme 19).84,84a 84c Similar rhodium-mediated borylations are known (Equation (90)).85... 

Optically active aldehydes are important precursors for biologically active compounds, and much effort has been applied to their asymmetric synthesis. Asymmetric hydroformylation has attracted much attention as a potential route to enantiomerically pure aldehyde because this method starts from inexpensive olefins and synthesis gas (CO/H2). Although rhodium-catalyzed hydrogenation has been one of the most important applications of homogeneous catalysis in industry, rhodium-mediated hydroformylation has also been extensively studied as a route to aldehydes. 

Kotha and Brahmachary353 prepared some constrained a-amino acids using a rhodium mediated [2 + 2 + 2] cycloaddition reaction. The indane type of a-amino acids were synthesized by reacting diynes with monoynes using Wilkinson s catalyst354. Thus, the reaction of diyne 615 with 616 afforded a-amino acid derivative 617 (equation 176). 

Catalysts 1, 3 and 5 employed in the modification of a polyhydrosiloxane chain via rhodium mediated Si-H addition to a C-C double bond appeared to be very efficient in giving a high conversion of Si-H bonds. With 1, the catalytic activity of the catalyst portion initially used remained unchanged even up to 10 cycles this makes these catalysts suitable for use in the commercial synthesis of modified polysiloxanes. 

Rhodium catalysis has played a critical role in the development of this type of reaction. The rhodium-mediated [4 + 2] carbocyclization between dienes and unactivated olefins or alkynes is a notable early example of this concept [2]. Further investigations demonstrated the extension of this methodology to the reaction between a diene and an allene [3]. Expansion of the scope of this strategy, to both the intra- and intermolecular [5-1-2] homologs of the Diels-Alder reaction, was accomplished with a vinylcyclopropane and either an alkyne or an olefin to afford the carbocyclization adducts (Scheme 11.1) [4, 5]. 

An understanding of the mechanism [10] for rhodium-mediated intramolecular C-H insertion begins with the recognition that these a-diazo carbonyl derivatives can also be seen as stabilized ylides, such as 15 (Scheme 16.4). The catalytic rhodium(II) car-boxylate 16 is Lewis acidic, with vacant coordination sites at the apical positions, as shown. The first step in the mechanism, carbene transfer from the diazo ester to the rhodium, begins with complexation of the electron density at the diazo carbon with an open rhodium coordination site, to give 17. Back-donation of electron density from the proximal rhodium to the carbene carbon, with concomitant loss of N2, then gives the intermediate rhodium carbene complex 18. 

A central assumption of this mechanism is that the actual C-H insertion is concerted, and that it proceeds with retention of absolute configuration. We had already, in a related case [12], demonstrated that rhodium-mediated C-H insertion proceeds with retention of absolute configuration. 

Sterically (Mechanics), there is no significant energy difference between the competing transition states 22 and 23. We therefore assume that the difference is electronic, and that conformation 22 makes electron density more readily available from the target C-H bond than does conformation 23. This interplay between steric and electronic effects will be important throughout this discussion of rhodium-mediated intramolecular C-H insertion. 

Using this approach, we have successfully predicted the major product from the cyclization of more than 30 a-diazo esters and a-diazo yS-keto esters [15]. Not all rhodium-mediated intramolecular C-H insertion reactions will proceed to give a single dominant diastereomer. Our interest in this initial investigation was to develop a model for the transition state that will allow us to discern those cyclizations that will proceed with high diastereoselectivity. 

While we have had some success, we are aware of the hmitations inherent in a transition state model for rhodium-mediated C-H insertion that attempts to predict product ratios on the basis of Mechanics calculations. Arbitrary decisions limiting the several degrees of freedom possible in the transition state could lead one to a model for the point of commitmenf to cyclization that would be far from reahty. The work described herein is important because it offers experimental evidence for a key rotational degree of freedom in the dihedral angle between the ester carbonyl and the rhodium carbenoid. 

Our initial objective, in this investigation, had been to design a useful chiral auxihary. We were pleased to find that naphthylborneol 31, upon optimization of the catalyst and the reaction temperature, served effectively. Until useful chiral catalysts are developed, naphthylborneol 31 will be of significant practical value for directing the absolute course of cyclopentane construction by rhodium-mediated intramolecular C-H insertion. 

We had expected that we might observe some correlation between two or more of these four measures of reactivity, but in fact plots of one versus the other showed no such correlation. We project that the study outlined here will lay the basis for a more detailed understanding of the mechanism of rhodium-mediated intramolecular C-H... 

Cyclopentane construction by rhodium-mediated intramolecular C-H insertion has been established as a powerful tool for the construction of carbocycHc systems, but there is much yet to be learned about the factors governing selectivity in the C-H insertion process [33]. We look forward to exciting developments in this area in years to come. 

For general reviews of rhodium mediated C-H insertions, see (a) Taber, D.F. Comprehensive Organic Synthesis Pattenden G., Ed., Pergamon Press Oxford, 1991 Vol. 3, pp. 1045-1062. (b) Padwa, A. ... 

Preliminary efforts to examine the mechanism of C-H amination proved inconclusive with respect to the intermediacy of carbamoyl iminoiodinane 12. Control experiments in which carbamate 11 and PhI(OAc)2 were heated in CD2CI2 at 40°C with and without MgO gave no indication of a reaction between substrate and oxidant by NMR. In Hne with these observations, synthesis of a carbamate-derived iodinane has remained elusive. The inability to prepare iminoiodinane reagents from carbamate esters precluded their evaluation in catalytic nitrene transfer chemistry. By employing the PhI(OAc)2/MgO conditions, however, 1° carbamates can now serve as effective N-atom sources. The synthetic scope of metal-catalyzed C-H amination processes is thus expanded considerably as a result of this invention. Details of the reaction mechanism for this rhodium-mediated intramolecular oxidation are presented in Section 17.8. 

Chemical Aspects of Rhodium-Mediated 1,3-Dipolar Cycloaddition... 

A rhodium-mediated carbonyl ylide approach to di- and tetrahydrofurans (Scheme... 

Although Padwa et al. (25) extensively studied and developed sihcon mediated technologies in azomethine ylide generation, he also developed other entries into azomethine ylides. In particular, the development of rhodium mediated transmuta-... 

Rhodium-mediated decomposition (60) of diazoamide (158) led to formation of the mesoionic oxazolium ylide 159, which was efficiently trapped by the pendant alkene to produce the oxo-bridged tricyclic amide 160. 

Peptide-Based Oxazoles by Rhodium-Mediated Carbenoid Insertion of Diazocarbonyl Compounds into an Amide N-H Bond Followed by... 

Substituted 4,5-dihydroazepines 321 (e.g., R1 = Bn, R2 = R3 = H, R4 = M e 82% yield) may be prepared in high yield by a rhodium-mediated hetero-[5+2]-cycloaddition of the cyclopropyl imines derived from 318 on reaction with the primary amines 319, with dimethyl acetylenedicarboxylate 320 (Equation 48) <2002JA15154>. 

M. C. Pirrung and Y. R. Lee, Hydroxy direction of the rhodium-mediated dipolar cycloaddition of cyclic carbenoids with vinyl ethers, J. Chem. Soc., Chem. Commun., (1995) 673-674. 

A few experiments have been performed to evaluate the potential of the P-menthyl-substituted class of phosphe-tanes 76 in rhodium-mediated alkene-hydrogenation reactions <1998S1539>. Within this series, monodentate ligands show low catalytic activity and poor enantioselectivity when employed in the hydrogenation of model dehydroamino acid derivatives. This observation is clearly consistent with the observed lability of their rhodium complexes, due to steric hindrance. 

Scheme 6.12 Rhodium-mediated coupling of cinnamyl alcohol andp-tolylboronic acid...

A key feature of intramolecular C-H insertion is the inherent ability to transform an acyclic tertiary stereogenic center into a cyclic quaternary stereogenic center, with retention of absolute configuration [12]. This was first demonstrated by rhodium-mediated cyclization of 29 to 30, leading to (+)-a-cuparenone (31) [13]. 

The a-diazocarbonyl derivatives used in these studies are easily prepared, and the rhodium-mediated cyclizations proceed rapidly, with high catalyst turnover (ca. 100-1000). The catalysts are stable at room temperature for years, and are not air sensitive. The reactions work best in inert solvents such as dichlor-omethane or benzene, and the solvent must be dry. Slow addition of the diazocarbonyl compound to the catalyst is not usually necessary. 

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