Indoles asymmetric reduction

Asymmetric reduction of carbonyls has also been achieved by Dupas and coworkers by reaction of achiral NADH equivalents mediated by chiral aluminum Lewis acids [23]. They reduced methyl benzoyl formate with the dihydropyrido[2,3-h]indole 86 and chiral aluminum Lewis acids whose structures are drawn and 89 and 90 (Sch. 12). Asymmetric induction was quite low. Details of the reaction, including the conditions used, were not provided nor were the procedures used for the preparation of the chiral Lewis acids 89 and 90. 

Synthesis of left-hand segment began with 7-benzyloxyindole 197. A Vilsmeier-Haack formylation followed by condensation afforded nitroalkene 198. Reduction, acylation with succinic anhydride, and subsequent Bischler-Napieralski cyclization provided dihydro-p-carboline 199. Noyori asymmetric reduction of 199, further treatment with A-iodosuccinimide, followed by activation with silver triflate in the presence of dimethoxy-N,N-diallylaniline furnished the desired coupling product 200. Subsequent saponification and cyclization via a ketene intermediate gave the rearrangement precursor 201. Oxidative skeletal rearrangement initiated by m-CPBA followed by removal of the Fmoc group and conversion of the aniline to the hydrazine furnished Fischer indole precursor 202 (Scheme 35). 

K. Takahashi, H. Yokomizo, K. Ishiyama, M. Kitsuta, M. Ohashi, New aspects of cyclodextrin chemistry induced by outside type complex formation asymmetric reduction of indol-3-pyruvic acid with NaBH4, J. Incl. Phenom. Macrocyc. Chem., 2006, 56, 95-99. 

The direct asymmetric reduction of unprotected l//-indoles to chiral indolines with up to 93% ee progressed via electrophilic indolenium ions formed by C(3) protonation by in situ generated HCl the chiral Lewis base (149) then mediated enantioselective hydride transfer from HSiCl3. ... 

Enantioselective hydrogenation of pyrroles has also been conducted, and is somewhat more complex than that of indoles. These reactions were conducted with N-Boc-substituted pyrroles and a ruthenium-TRAP catalyst. The pyrroles can be mono-, di-, or tri-substituted. For example, the asymmetric reduction of 4,5-dimethylpyrrole-2-carboxylate gave the product from addition of hydrogen to the same face of both olefin units to form products containing three stereocenters in high enantioselectivity. These reactions occur by initial reduction of the less-substituted carbon-carbon double bond. 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Kadyrov R, Riermeier TH (2003) Highly enantioselective hydrogen-transfer reductive amination catalytic asymmetric synthesis of primary amines. Angew Chem Int Ed Engl 42 5472-5474 Kang Q, Zhao ZA, You SL (2007) Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. J Am Chem Soc 129 1484-1485... 

The asymmetric reaction of cyclic ketones can be performed with chiral bi-naphthylphosphines (Eq. 8) [47-50]. The reaction of acetophenones with ortho-bromonitrobenzenes followed by reduction affords indole derivatives (Eq. 9)... 

Davies has further exploiled his previously reporied approach to (he tropanc skeleton related to cocaine based on the rhodium catalyzed decomposition of the vinyidiazomethane 81 in the presence of A/-Boc-pyrroIe (82) <01BMCL487>. Reduction of the non-conjugated double bond followed by A -deprotection and N-alkylation provided substrate 83 which was susceptible to conjugate addition of nucleophiles such as 84 in the presence of CuBr to afford 3-p-aryl tropanes which exhibited potent binding affinity for both the dopamine and serotonin transporters. Additionally, this author described the synthesis of various methyl heteroaryldiazoacetate analogues of 81, (me of which possessed an indole function, for use in catalytic asymmetric cyclopropanations . 

Dixneuf, Bruneau and coworkers have reported an interesting reduction of the unsaturated acyl oxazolidinone (2.90). The reduction works with high yield and asymmetric induction, and the product (2.91) is effectively propionic acid with a chiral auxiliary attached. The chiral auxiliary was then used to induce asymmetry in a subsequent step. 2,3-Substituted N-Boc indoles imdergo hydrogenation to... 

A pioneering application of C-H activation to natural-product synthesis is in a synthesis of ibogamine 3.24 (Scheme 3.11). ° An asymmetric Diels-Alder reaction set up the chirality. The chirality was controlled by the use of a chiral auxiliary on the diene 3.18. Reductive amination then connected the Diels-Alder product 3.19 to an indole moiety. Palladium-catalysed cyclization then generated the bicyclic alkene 3.23. In this reaction. 

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