Asymmetric synthesis ketone arylation

A-Boc-leucinal may react with allyl- and alkenyhnagnesium hahdes giving syn- and awf/-products in ca 9 1 ratio. This method was used for the asymmetric synthesis of important amino acids like statine and norstatine. An enantioselective desymmetrization of anhydrides was reported. Arylmagnesium chlorides react in toluene in the presence of (—)-sparteine (1 equiv.) with 3-substituted glutaric anhydrides 215, giving aryl ketones with 87-92% ee (equation 145). ... 

Asymmetric induction has also been evaluated in the reaction of a-aryl substituted ketones, esters, and lactones (43). The potential of the method is demonstrated by the synthesis of some naturally occurring or nonnaturally occuring chiral compounds (Scheme 15). Similarly, asymmetric synthesis of ( — )-physostigmine, a clinically useful anticholinesterase agent, is accomplished by using phase-transfer alkylation of... 

Catalytic asymmetric synthesis of enantiopure diaryl-methanols and -methylamines (important pharmaceutical intermediates) has been reviewed (76 references), focusing on (i) aryl transfers on to aryl-aldehydes and -imines and (ii) asymmetric reductions of diaryl-ketones and -ketoimines.284... 

The asymmetric hydrogenation of aryl ketones is an important step in the synthesis of many pharmaceutical intermediates. Blaser and co-workers showed that Ru complexes with Fe-cyclopentadienyl sandwich complexes are good catalysts for this reaction [63]. Figure 1.26 shows the different substrates tested, along with the time, conversion, and substrate/catalyst ratio. Using these data, calculate the catalyst TON and TOF in each case. 

There is no doubt that catalytic asymmetric synthesis has a significant advantage over the traditional diastereomeric resolution technology. However, it is important to note that for the asymmetric hydrogenation technology to be commercially useful, a low-cost route to the precursor olefins is just as crucial. The electrocarboxylation of methyl aryl ketone and the dehydration of the substituted lactic acids in Figures 5 and 6 are highly efficient. Excellent yields of the desired products can be achieved in each reaction. These processes are currently under active development. However, since the subjects of electrochemistry and catalytic dehydration are beyond the scope of this article, these reactions will be published later in a separate paper. 

The oxazaborolidine-catalyzed enantioselective reduction of aryl alkyl ketones was used in the asymmetric synthesis of the naturally occurring molecule (15 )-(—)-salsolidine 4119 (Scheme 4.3o). The ketone 42 underwent oxazaboroli-dine-mediated reduction to furnish the alcohol 43 in excellent yield and greater than 95% ee. The alcohol 43 was then coupled with the reagent 44 under Mit-sunobu conditions to produce the aminoacetal 45. 

Asymmetric reduction of ketones. A complex hydride reagent (2) is prepared in I HF by reaction of equimolar amounts of LiAlH, optically active S)-l, and ethanol. This reagent effects asymmetric reduction of aryl and alkenyl ketones with high enantioselectivity. Reductions of dialkyl ketones are less selective (e.g., 13% ec for benzyl methyl ketone). This method has also been applied to ketones that are intermediates in prostaglandin synthesis. ... 

In an industrial asymmetric synthesis en route to the antiinflammatory agent naproxen, the dimethyl L-tartrate acetals of ethyl aryl ketones are brominated in high yield and selectivity to give the corresponding a-bromo derivatives. Subsequent stereospecific Ag -promoted 1,2-aryl migration provides the 2-alkyl-2-arylacetic acid after hydrolysis of the tartrate auxiliary, which is recovered (e.g. eq 4). 

PALLADIUM-CATALYSED MULTIPLE AND ASYMMETRIC ARYLATIONS OF VINYL ETHERS CARRYING CO-ORDINATING NITROGEN AUXILIARIES SYNTHESIS OF ARYLATED KETONES AND ALDEHYDES... 

L. R. Reddy, N. Bhanumathi, K. R. Rao, D5mamic kinetic asymmetric synthesis of j8-aminoalcohols from racemic epoxides in cyclodextrin complexes under solid state conditions, Chem. Commun., 2000, 2321-2322, M. A. Reddy, N. Bhanumathi, K. R. Rao, Asymmetric synthesis of 2-azido-l-arylethanols from azido aryl ketone-j3-cyclodextrin complexes and sodium borohydride in water, Chem. Commun., 2001, 1974-1975. 

Springer International Publishing Switzerland 2015 R. Doran, Asymmetric Synthesis of Bioactive Lactones and the Development of a Catalytic Asymmetric Synthesis of a-Aryl Ketones, Springer Theses, DOI 10.1007/978-3-319-20544-l l... 

Introduction to the Development of a Catalytic Asymmetric Synthesis of Tertiary a-Aryl Ketones... 

Despite the number of reports of the asymmetric synthesis of tertiary a-aryl cyclohexanones, there have only been three reports which describe the asymmetric synthesis of tertiary a-aryl cyclopentanones. The first of these was reported by Shi via asymmetric epoxidation of benzylidene cyclobutanes and epoxide rearrangement in a subsequent step [76]. Backvall used a dynamic kinetic resolution of aUyhc alcohols-aUylic substitution-oxidative cleavage sequence to access 2-phenylcyclopentanone [77]. The first direct catalytic asymmetric synthesis of tertiary a-aryl ketones was recently described by Kingsbury using a series of Sc-catalysed diazoalkane-carbonyl homologations with bis/tris oxazohne ligands [78]. 

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