Enantioselective synthesis ketones

The Pictet-Spengler condensation has been of vital importance in the synthesis of numerous P-carboline and isoquinoline compounds in addition to its use in the formation of alkaloid natural products of complex structure. A tandem retro-aldol and Pictet-Spengler sequence was utilized in a concise and enantioselective synthesis of 18-pseudoyohimbone. Amine 49 cyclized under acidic conditions to give the condensation product 50 in good yield. Deprotection of the ketone produced the indole alkaloid 51. 

This ligand has also been used by the same authors to promote the addition of ZnMe2 to a functionalised a,(3-unsaturated ketone in the asymmetric key step of the first enantioselective synthesis of (-)-frontalin. This synthesis started with the naphthalene-catalysed lithiation of a chlorinated ketal (Scheme 4.15) that, after several transmetalation processes, was trapped by reaction... 

The (2S,4S)-MCCPM-Rh(I) complex was found previously by Achiwa and colleagues to be an efficient catalyst for the enantioselective hydrogenation of /9-amino ketone derivatives, leading to a practical enantioselective synthesis of (F)-fluoxetine [N-methyl-3-(4-trifluoromethylphenoxy)-3-phenylpropylamine] hydrochloride [22 b]. Moreover, the use of AMPP ligands again proved to be efficient for these substrates, as exemplified in Table 33.6 [15 i],... 

Enantioselective synthesis of a-hydroxy phosphonates can also be achieved by asymmetric oxidation with camphorsulfonyl oxaziridines (Scheme 2-60).156 Reasonable yields can usually be obtained. (+)-147a or (+)-147b favors formation of the (S )-product, as would be expected, because these oxidations proceed via a transition state that parallels that previously discussed for the stereoselectivity observed with ketones.157... 

Hoppe D, Marr F, Bruggemann M (2003) Enantioselective Synthesis by Lithiation Adjacent to Oxygen and Electrophile Incorporation. 5 61-138 Hou Z, Wakatsuki Y (1999) Reactions of Ketones with Low-Valent Lanthanides Isolation and Reactivity of Lanthanide Ketyl and Ketone Dianion Complexes. 2 233-253 Hoveyda AH (1998) Catalytic Ring-Closing Metathesis and the Development of Enantioselective Processes. 1 105-132 Huang M, see Wu GG (2004) 6 1-36... 

Nucleophilic additions to (cyclohexadienone)Fe(CO)3 complexes (218) occur in a dia-stereospecific fashion (Scheme 56)197. For example, the Reformatsky reaction of ketone (218a) affords a simple diasteromeric alcohol product19715. The reduction of (1-carbo-methoxycyclohexa-l,3-dien-5-one)Fe(CO)3 (218b) to give 219 has been utilized in the enantioselective synthesis of methyl shikimate. In a similar fashion, cycloadditions of (2-methoxy-5-methylenecyclohexa-l,3-diene)Fe(CO)3 (220) occur in a diastereospecific fashion198. 

Retrosynthetic analysis of 5 and 6 yielded ketone 7 as pivotal intermediate. A key reaction for the synthesis of 7 was the auxiliary-controlled, di-astereoselective biaryl coupling of a phenyl magnesium bromide (from 8 or 9) with aryloxazoline 10 (Scheme 1). This coupling strategy was developed in the Meyers laboratory [12] and previously applied to the enantioselective synthesis of other naturally occurring biaryl lignans, such as steganone [13]. 

More recently a rhodium-catalyzed enantioselective synthesis of duloxetine (3) has been reported (Scheme 14.17). In this work, readily available amino ketone 51 was converted to (6)-aminoalcohol 36 in 75% yield and greater than 99% ee. The intermediate alcohol was subsequently converted into duloxetine (3) in a single step via standard etherification. 

After the successful asymmetric synthesis of a-substituted P-amino ketones (R)-14, we envisaged the diastereo- and enantioselective synthesis of a,P-disubstituted Mannich bases. As shown in Scheme 1.1.4, we were able to use benzaldehyde-N-phenylimine [11] as well as a-alkoxycarbonylaminosulfones [12] as Mannich electrophiles to synthesize in good overall yields and high de- and ee-values the anti-configured P-amino ketones (R,S)-15 and (R,S)-16, respectively [13]. 

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