Enamide chiral

Asymmetric cyclization using chiral ligands has been studied. After early attempts[142-144], satisfactory optical yields have been obtained. The hexahy-dropyrrolo[2,3-6]indole 176 has been constructed by the intramolecular Heck reaction and hydroaryiation[145]. The asymmetric cyclization of the enamide 174 using (S j-BINAP affords predominantly (98 2) the ( )-enoxysilane stereoisomer of the oxindole product, hydrolysis of which provides the ( l-oxindole aldehyde 175 in 84% yield and 95% ec. and total synthesis of (-)-physostig-mine (176) has been achieved[146]. 

N O Y O R I Chiral homogeneous hydrogenation Homogeneous chiral hydrogenation ol unsaluraled alcohols, or cartMxyNc acids, enamides, ketones in the presence ol BINAP Ru or Rh complex 8 as catalyst. 

A series of chiral binaphthyl ligands in combination with AlMe3 has been used for the cycloaddition reaction of enamide aldehydes with Danishefsky s diene for the enantioselective synthesis of a chiral amino dihydroxy molecule [15]. The cycloaddition reaction, which was found to proceed via a Mukaiyama aldol condensation followed by a cyclization, gives the cycloaddition product in up to 60% yield and 78% ee. 

A representative example is the cyclic enamide 1, containing an optically active A-camphanoyl substituent as a chiral auxiliary82. Treatment of 1 at — 78 C with hydrogen chloride and then a Lewis acid leads to the chiral A -acyliminium intermediate that is alkylated with high stereoselectivity to provide optically active piperidine derivatives. 

Enamide hydrogenations have become a routine test reaction for evaluation of the effectiveness of new chiral Hgands [5,11,20,56,59,104]. In addition to being a test reaction, it stands as one of the most powerful and economic methods for the production of enantiomerically pure a-amino acid derivatives. Our group... 

The asymmetric reduction of enamides using hydrogenation conditions is a well documented reaction with a number of groups reporting excellent results [14]. Syn delivery of hydrogen from the same face of the molecule ensures that the enamide geometry defines the relative stereochemistry obtained, and a range of chiral catalysts have been developed to control the absolute stereochemistry. However, a... 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

High facial diastereoselectivity has been reported in the [2+2] photocycloaddition of aromatic aldehydes with a chiral enamide to give the ds-2,3-disubstituted oxetanes 11 and 12 with only minor amounts of the trans-oxetanes <99TL9003>. The same group of workers have investigated the photocycloaddition of m-substituted benzaldehydes to 3,4-dihydro-l.H-pyridin-2-ones to give mainly 13 <99JA10650>. 

In this reaction, a rhodium atom complexed to a chiral diphosphine ligand ( P—P ) catalyzes the hydrogenation of a prochiral enamide, with essentially complete enan-tioselectivity and limiting kinetic rates exceeding hundreds of catalyst turnovers per second. While precious metals such as Ru, Rh, and Ir are notably effective for catalysis of hydrogenation reactions, many other transition-metal and lanthanide complexes exhibit similar potency. 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

In addition to standard cyclic and acyclic enamides, the effective hydrogenation of several more unusual enamides has been reported (Fig. 24.13). A concise method for the synthesis of chiral yS-amino alcohols, amino oximes and chiral 1,2-diamines has been described by Burk et al. via the enantioselective hydroge-... 

One method of accessing chiral alcohols is through the enantioselective hydrogenation of the corresponding enol acetates. Despite this substrate class having similar structures to enamides, far fewer successful examples of this reaction... 

Until now, only a few effective ligands of this type have been identified (Fig. 25.4). Kagan and co-workers [5] prepared one of the few chiral diphosphines with only planar chirality and obtained 95% ee for the hydrogenation of DM IT with LI (Table 25.1, entry 1.1.), but enantioselectivities for several enamide derivatives were below 82% ee (the best results were with the cyclohexyl analogue of LI). For the reactions with DM IT or MAC, the cationic Rh-kephos complex showed comparable or better performance than corresponding duphos catalysts. 

Rh-catalyzed hydrogenation of simple enamides has attracted much attention recently. With the development of increasingly efficient chiral phosphorus ligands, extremely high ee-values can be obtained in the Rh-catalyzed hydrogenation of a-aryl enamides. E/Z-isomeric mixtures of -substituted enamides can also be hydrogenated, with excellent ee-values. Some efficient examples (>95% ee) of hydrogenation of a-phenylenamide and E/Z-isomeric mixtures of / -methyl-a-phenylenamide are listed in Table 26.3. 

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