Ketones, 3-asymmetric amino

Asymmetric Reduction of Aryl Alkyl Ketones with Amino Alcohol-LAH Reagents... 

Palmer, M.J., Kenny, J.A., Walsgrove, T., Kawamoto, A.M. and Wills, M., Asymmetric transfer hydrogenation of ketones using amino alcohol and monotosylated diamine derivatives of indane. 

The alkylation of metalated imines, hydrazones, 4,5-dihydrooxazoles, 4,5-dihydroisoxazoles, 5,6-dihydro-4/7-1,2-oxazines and 2,5-dialkoxy-3,6-dihydropyrazines (i.e., azaenolates) is a commonly used method in asymmetric synthesis of enantiomerically enriched aldehydes, ketones, spiroacetals, amines, /J-oxo esters, carboxylic acids, lactones, 1,3-amino alcohols, /(-hydroxy ketones and amino acids. 

I.4.I.2. Amino, Hydroxy, and Phenylthio Ketones Asymmetric hydrogenation of amino ketones, in either a neutral or hydrochloride form, has extensively been studied. Both Rh(I) and Ru(II) complexes with an appropriate chiral diphosphine give a high enantioselectivity. As described in Scheme 1.42, a-aminoacetophenone hydrochloride is hydrogenated using a cationic Rh complex with (R)-MOC-BIMOP, an unsymmetricaJ biaryl diphosphine, to give the... 

Since the discoveries of Itsuno32 and Corey,33 remarkable advances have been made in the enantio-selective reduction of prochiral ketones using amino alcohol-derived oxazaborolidines (see Chapter 16).34 35 In most cases, these amino alcohols were obtained from chiral pool sources. Consequently, extensive synthetic manipulations were often necessary to access their unnatural antipode. Didier and co-workers were first to examine the potential of m-aminoindanol as a ligand for the asymmetric oxazaborolidine reduction of ketones.36 Several acyclic and cyclic amino alcohols were screened for the reduction of acetophenone (Scheme 17.2), and m-aminoindanol led to the highest enantioselectivity (87% ee). 

It has long been possible to hydrogenate a wide range of functionalized ketones asymmetrically achieving selectivities of over 90 % ee. Thus, pharmaceutically important 1,2-amino alcohol derivatives have been available since 1979 with... 

Systematic studies on additions to 3-asymmetric amino ketones of general structure (48 equation 16) result in the following conclusions. ... 

Asymmetric amino acid synthesis. The reaction of aralkyl methyl ketones (2) with I as the chiral reagent in the presence of sodium cyanide in acetic acid affords... 

Asymmetric phase-transfer catalysis usually stands somewhat separate from the rest of asymmetric organocatalysis and has always been dominated by metal-free catalysts. The earliest report in asymmetric phase-transfer catalysis dates back 30 years to 1984 when Dolling and coworkers first reported the use of a quaternised Cinchona alkaloid (6) as a phase-transfer catalyst for the asymmetric alleviation of ketone 7 during an asymmetric synthesis of (- -)-Indacrinone (Scheme 1.5). Quaternised Cinchona alkaloids dominated the area of asymmetric phase-transfer catalysis for the rest of the 20th century, and were especially used as catalysts for asymmetric amino... 

Klingler FD (2007) Asymmetric hydrogenation of prochiral amino ketones to amino alcohols... 

The importance of chemical syntheses of a-amino acids on industrial scale is limited by the fact that the standard procedure always yields the racemic mixture (except for the achiral glycine H2N-CH2-COOH and the corresponding amino acid from symmetrical ketones R-CO-R). A subsequent separation of the enantiomers then is a major cost factor. Various methods for the asymmetric synthesis of a-amino acids on laboratory scale have been developed, and among these are asymmetric Strecker syntheses as well. ... 

In asymmetric Strecker synthesis ( + )-(45,55 )-5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane has been introduced as an alternative chiral auxiliary47. The compound is readily accessible from (lS,25)-2-amino-l-phcnyl-l,3-propancdioI, an intermediate in the industrial production of chloramphenicol, by acctalization with acetone. This chiral amine reacts smoothly with methyl ketones of the arylalkyl47 or alkyl series48 and sodium cyanide, after addition of acetic acid, to afford a-methyl-a-amino nitriles in high yield and in diastereomerically pure form. 

Several methods for asymmetric C —C bond formation have been developed based on the 1,4-addition of chiral nonracemic azaenolates derived from optically active imines or enamines. These methods are closely related to the Enders and Schollkopf procedures. A notable advantage of all these methods is the ready removal of the auxiliary group. Two types of auxiliaries were generally used to prepare the Michael donor chiral ketones, such as camphor or 2-hydroxy-3-pinanone chiral amines, in particular 1-phenylethanamine, and amino alcohol and amino acid derivatives. 

The reductive amination of ketones can be carried out under hydrogen pressure in the presence of palladium catalysts. However, if enantiopure Q -aminoketones are used, partial racemization of the intermediate a-amino imine can occur, owing to the equilibration with the corresponding enam-ine [102]. Asymmetric hydrogenation of racemic 2-amidocyclohexanones 218 with Raney nickel in ethanol gave a mixture of cis and trans 1,2-diamino cyclohexane derivatives 219 in unequal amounts, presumably because the enamines are intermediates, but with excellent enantioselectivity. The two diastereomers were easily separated and converted to the mono-protected cis- and trans- 1,2-diaminocyclohexanes 220. The receptor 221 has been also synthesized by this route [103] (Scheme 33). 

Although SiCh 57 has been employed, e.g., in the presence of sodium azide to convert ketones into tetrazoles (Section 5.3), to condense cyclopentanone in high yields into 1.2.3.4.5.6-tris(trimethylene)benzene (Section 9.2), or used for the condensation of amino acids to polyamides (Chapter 14) with formation of Si02, enol-trimethylsilyl ethers 107 a of ketones such as cyclohexanone are cleanly converted by SiCh 57 in the presence of Hg(OAc)2 into the trichlorosilylenol ether 116, which adds benzaldehyde in the presence of the asymmetric catalyst 117 to give... 

Asymmetric addition of acetylide to the ketone Having the two key reagents in hand, we optimized the asymmetric addition reaction on ketone 41. First, chiral modifiers were screened from among readily accessible P-amino alcohols and the results are summarized in Table 1.5. 

The overall process from amino ketone 36 to Efavirenz (1) required four steps with an overall yield of 72% and quite high purity of the isolated 1, as described above. This process supported initial marketing of Efavirenz but there were a few drawbacks. The key asymmetric addition of acetylide required 2equiv of precious cyclopropylacetylene (37). In addition, two steps out of the total four steps were protection with pMB and its deprotection. 

Here, we will discuss the reaction mechanism of the asymmetric lithium acetylide addition to pMB protected amino ketone 41. Then we will discuss some speculation about the asymmetric addition via the novel zinc acetylide addition. 

Organic-Base Catalyzed. Asymmetric direct aldol reactions have received considerable attention recently (Eq. 8.98).251 Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with chiral cyclic secondary amines as catalysts.252 L-proline and 5,5-dimethylthiazolidinium-4-carboxylate (DMTC) were found to be the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding... 

Among the most active catalysts for the asymmetric transfer hydrogenation of prochiral ketones and imines to chiral alcohols and amines are arene-ruthenium(II) amino-alcohol (or primary/ secondary 1,2-diamine)-based systems, with an inorganic base as co-catalyst, developed by Noyori139-141 and further explored by others (Scheme 27).142-145... 

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