Acetophenone derivatives, prochiral

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Assuming that the enantioselection mechanism for artificial transfer hydroge-nases using biotinylated d -piano-stool complexes should be similar to the homogeneous systems, we initially focused on the reduction of prochiral acetophenone derivatives [57-59]. Systematic variation of the pH revealed that these systems perform best at pH 6.25. As the pH rises during catalysis, we used a mixed buffer consisting of a sodium formate and boric acid mixture. Addition of MOPS further contributed to stabilization of the pH and improved the selectivity of the system. 

The hydride-donor class of reductants has not yet been successfully paired with enantioselective catalysts. However, a number of chiral reagents that are used in stoichiometric quantity can effect enantioselective reduction of acetophenone and other prochiral ketones. One class of reagents consists of derivatives of LiAlH4 in which some of die hydrides have been replaced by chiral ligands. Section C of Scheme 2.13 shows some examples where chiral diols or amino alcohols have been introduced. Another type of reagent represented in Scheme 2.13 is chiral trialkylborohydrides. Chiral boranes are quite readily available (see Section 4.9 in Part B) and easily converted to borohydrides. 

A different MS-based ee-assay makes use of a proline-derived mass-tagged acylating agent.95 In the course of derivatization it is necessary that some degree of kinetic resolution comes about. The sensitivity of the method was reported to be 10% ee. It can also be applied to the reaction of a prochiral compound lacking enantiotopic groups, as in the transformation of acetophenone to phenylethanol. 

Sinou and coworkers evaluated a range of enantiopure amino alcohols derived from tartaric acid for the ATH reduction of prochiral ketones. Various (2R,iR)-i-amino- and (alkylamino)-l,4-bis(benzyloxy)butan-2-ol were obtained from readily available (-I-)-diethyl tartrate. These enantiopure amino alcohols have been used with Ru(p-cymene)Cl2 or Ir(l) precursors as ligands in the hydrogen transfer reduction of various aryl alkyl ketones ee-values of up to 80% have been obtained using the ruthenium complex [93]. Using (2R,3R)-3-amino-l,4-bis(benzyloxy)butan-2-ol and (2R,3R)-3-(benzylamino)-l,4-bis(benzyloxy)butan-2-ol with [lr(cod)Cl]2 as precursor, the ATH of acetophenone resulted in a maximum yield of 72%, 30% ee, 3h, 25 °C in PrOH/KOH with the former, and 88% yield, 28% ee, 120 h with the latter. 

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). 

The reduction of prochiral and/or sterically hindered ketones with and ammonium cations 40a, b derived from ephedrine afforded optically active alcohols in optical yields up to 13.7% the Edition of nitromethane to chalcone in the presence of KF occurs with an enantiomeric excess up to 26.2% . In the case of the reduction of ketones, the asymmetric induction dropped to values very close to zero for substrates lacking appreciable steric hindrance near the carbonyl group such as 2-octanone, acetophenone or propiophenone (Eq. (30)). 

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