Rhodium-catalyzed C—H amination

Scheme 17.23 Sulfamide substrates for rhodium-catalyzed C-H amination...

The use of substrate control in rhodium catalyzed C H aminations is covered in detail in Espino and Du Bois recent review of rhodium catalyzed oxidative amina tion [51]. A brief summary of relevant material is provided here, leading to a discussion of recent advances in the synthesis of chiral amines from achiral substrates. Rhodium catalyzed C H amination proceeds via a concerted insertion process rendering it a stereospecific transformation. Thus, the appropriate choice of an enantioenriched starting material can facilitate the synthesis of enantioenriched amines, which would often be particularly difficult to access in any other manner. As exemplified in Scheme 12.9, the C H insertion reaction of enantiomerically pure carbamate 9 was accomplished with complete retention of configuration providing the chiral oxazolidinone 10 in greater than 98% ee [13]. 

J. Du Bois, Rhodium catalyzed C-H amination and enabling method for chemical synthesis. Organic Process Research and Development 15 758-762 2011. 

Good to excellent diastereoselectivities, favoring the syn-product are obtained for the rhodium-catalyzed C—H amination with a- and P-substituted sulfamates (Figure 5.1) [65]. 

A titanium-mediated amination followed by a directed rhodium-catalyzed C-H functionalization of an olefinic C-H leads to heterocycles (Equation (184)).149... 

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. 

Attempts have recently been made to extend the scope of rhodium-catalyzed C-H alkynylation beyond olefins and arenes functionalization via a classical five-membered metalacycle. Li and co-workers developed the directed C-H alkynylation of benzaldehydes (Scheme 24) [140]. Both alcohols and sulfonyl amines could be used as directing groups. With alcohols, an iridium catalyst in methanol was used, giving ynones in good yields. With sulfonyl amines the best results were obtained with a rhodium catalyst in dichloromethane. 

Scheme 40 Rhodium- and silver-catalyzed C—H amination of pleuromutilin carbamate 39.

An elegant example of the cascade processes involving rhodium-catalyzed C—H bond activation is the three-component reaction of benzaldehydes, amines, and alkynes, which led to the one-pot synthesis of isoquinoUnium salts 58 (Scheme 5.39) [39], The process involves generation of imine, C—H bond activation, and annula-tion. The mechanism proposed is strongly supported by the isolation of the five-membered rhodacycle A and an intermediate (Scheme 5.40). The significance of this cascade C—H activation/annulation reaction has been demonstrated by its application to the total synthesis of the isoquinohnone alkaloid oxychelerythrine 59 with excellent yield (Scheme 5.41). 

Various chiral amines were tested and the best selectivi-ties and yields were obtained with chiral benzylic amines, particularly with aminoindane derivatives. After acidic hydrolysis, the rhodium-catalyzed C H functionalization led to the aldehyde 58. Whatever the aminoindane derivative used, the yields and selectivities were good and the 7-fluoroaminoindane was the best chiral auxiliary (70% yield, 90% ee). After recrystaUization, the chiral aldehyde 58 was isolated in 99% ee and then used in a Knoevenagel condensation. During this late reaction, the C-20 position has been epimerized to give the more stable thermodynamic anti-diastereoisomer 57 as the major product. The total synthesis... 

Scheme 17.6 Stereospecific C-H amination under rhodium-catalyzed conditions.

Intramolecular C-H Amination with Rhodium(II) Catalysts 391 Tab. 17.2 Rhodium-catalyzed insertion of sulfamates. 

Padwa has shown that rhodium-catalyzed oxidation of indolyl carbamate 67 employing either Phl(OAc)2 or Phl=0 follows a path similar to that of the D-aUal carbamate (Scheme 17.26) [95]. In principle, indole attack of the putative rhodium-nitrene generates zwitterion 68, which is trapped subsequently by an exogenous nucleophile. Spiro-oxazolidinone products (for example, 69) are isolated as single diastereomers in yields ranging from 50 to 85%. As an intriguing aside, Padwa has found that certain carbamates react with Phl=0 in the absence of any metal catalyst to furnish oxazoHdinone products. This result may have implications for the mechanism of the rhodium-catalyzed process, although it should be noted that control experiments by Espino and Du Bois confirm the essential role of the metal catalyst for C-H amination [57]. 

Asymmetric C-H amination has progressed through the apphcation of rathenium(II) porphyrin catalysts. Che has employed fluorinated ruthenium porphyrin complexes with added AI2O3 (in place of MgO) to catalyze suifamate ester insertion (Scheme 17.31) [98]. These systems show exceptional catalyst activity (>300 turnovers) and afford product yields that are comparable to rhodium tetracarboxylate-promoted reactions. Of perhaps greater significance is that the use of the chiral rathenium complex... 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

Recently, efficient rhodium-catalyzed intermolecular C—H amination reactions have been reported where a sulfonimidamide is used as the nitrene precursor [46]. The functionalizations of various C—H bonds proceed smoothly in this type of intermolecular amidation reaction (Equation 11.20) [47]. When chiral sulfonimida-mides are used, moderate to excellent diastereoselectivities can be achieved. 

Rhodium dimer complexes are the most widely used catalysts to perform C—H aminations. Other metal complexes that catalyze metal nitrene C—H insertion reactions, include metalloporphyrins [12, 39], silver [21, 40], copper [22], palladium [41] and gold [42] complexes. 

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