H«- amine

In 1982, Breslow and coworkers reported the first example of iron-catalyzed nitrene C-H bond insertion [29]. They used [Fe(TTP)] as catalyst and PhINTs as nitrene precursor to achieve C-H bond amination of cyclohexane. However, the product yield was low (around 10%). Subsequently, the same authors found that iminoio-dane 7 derived from 2,5-diisopropylbenzenesuIfonamide underwent intramolecular C-H amination efficiently with [Fe(TPP)Cl] as catalyst at room temperature, giving the insertion product in 77% yield (Scheme 29) [85]. 

The transition metal-catalyzed C-H insertion reaction of carbenes to organic compounds is a well-established synthetic method, as shown in the first two sections in this chapter. However, nitrene C-H insertion, the corresponding reaction of carbene analog, is much less known. In the past decade, considerable advances have been made in the development of this chemistry into a generally useful C-H amination process by using improved catalysts and protocols, in which readily available amines or amides are used as the starting substrates. Moreover,... 

As shown in the previous two sections, rhodium(n) dimers are superior catalysts for metal carbene C-H insertion reactions. For nitrene C-H insertion reactions, many catalysts found to be effective for carbene transfer are also effective for these reactions. Particularly, Rh2(OAc)4 has demonstrated great effectiveness in the inter- and intramolecular nitrene C-H insertions. The exploration of enantioselective C-H amination using chiral rhodium catalysts has been reported by several groups.225,244,253-255 Hashimoto s dirhodium tetrakis[A-tetrachlorophthaloyl-(A)-/ r/-leuci-nate], Rh2(derived rhodium complex, Rh2(i -BNP)4 48,244 afforded moderate enantiomeric excess for amidation of benzylic C-H bonds with NsN=IPh. 

Metal porphyrins have been employed for intermolecular G-H amination with allylic, benzylic, and some saturated... 

Metal/Ligand Imine Reaction time (h) Amine Yield [%) e.e. (%) (config.)... 

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

Muller has explored enantioselective C-H insertion using optically active rhodium complexes, NsN=IPh as the oxidant, and indane 7 as a test substrate (Scheme 17.8) [35]. Chiral rhodium catalysts have been described by several groups and enjoy extensive application for asymmetric reactions with diazoalkanes ]46—48]. In C-H amination experiments, Pirrung s binaphthyl phosphate-derived rhodium system was found to afford the highest enantiomeric excess (31%) of the product sulfonamide 8 (20equiv indane 7, 71% yield). 

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. 

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

The established activity of ethereal a-C-H bonds toward carbene and nitrene insertion has evoked new applications for sulfamate oxidation [76-78] In principle, a C-H center to which an alkoxy group is attached should be a preferred site for amination irrespec-hve of the addihonal functionality on the sulfamate ester backbone (Scheme 17.20). Such a group can thus be used to control the regiochemistry of product formation. The N,0-acetal products generated are iminium ion surrogates, which may be coupled to nucleophiles under Lewis acid-promoted conditions [79]. This strategy makes available substituted oxathiazinanes that are otherwise difficult to prepare in acceptable yields through direct C-H amination methods [80]. 

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

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]. 

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