Catalytic Asymmetric Synthesis of α ..

N2 - Chemical equations presented. A simple and efficient method for the preparation of β-stereogenic α-keto esters is described using a copper(II)-catalyzed aerobic deacylation of substituted acetoacetate esters. The substrates for the title process arise from catalytic, enantioselective conjugate additions and alkylation reactions of acetoacetate esters. The mild conditions do not induce racemization of the incipient enolizable α-keto ester. The reaction is tolerant of esters, certain ketones, ketals, and nitro groups and utilizes inexpensive, readily available materials.

A general catalytic asymmetric reductive aldol reaction of allenic esters to ketones is described

In 2008, Lim and Coltart introduced the N- () chiral auxiliaries for the asymmetric alkylation of ketones. In contrast to other methods, these auxiliaries are both easily introduced into and removed from ketones, with near quantitative recovery of the auxiliary. Furthermore, deprotonation of the hydrazones is rapid, and alkylation does not require extreme low temperature; yet it proceeds with excellent stereoselectivity and consistently high yields. Of the ACCs examined to date, the camphor-derived auxiliary has proven to be the most versatile and can be used in the alkylation of a wide range of substrates (Figure ). The structurally more simple phenyl alanine-derived auxiliary produces equally high levels of selectivity with certain types of ketones, as discussed in the next section. With regard to regioselectivity, deprotonation of ACC hydrazones occurs in a manner that is fundamentally different than for ketones, SAMP/RAMP and other dialkyl hydrazones, and imines. This enables regiocontrolled alkylations to be carried out that are not possible using any other means, such as the α,α-bisalkylation of ketones possessing both α- and α'-protons. The Coltart group has employed ACC auxiliaries for the asymmetric synthesis of several biologically important compounds.


Asymmetric α-Alkylation of Aldehydes, Ketones, ..

A catalytic asymmetric synthesis of β-hydroxy-α-amino acid esters was developed using the direct aldol reaction of glycinate Schiff bases with aldehydes.

As early as 1976, azaenolates derived from N,N-dialkyl hydrazones were studied as an alternative to direct ketone and aldehyde enolate alkylations. These species were found to exhibit higher reactivity toward electrophiles, as well as better regioselectivity for C-alkylation than their parent carbonyl compounds. N,N-dialkyl hydrazones are stable and are relatively easy to prepare, making them appealing from a practical point of view in comparison with imines and enamines, which can be difficult to form quantitatively and are hydrolytically unstable. Given these desirable attributes, Enders undertook the development of chiral nonracemic N,N-dialkyl hydrazine auxiliaries for the asymmetric α-alkylation of ketones. The result of his efforts were (S)- and (R)-1-amino-2-methoxypyrrolidine hydrazine ( and , respectively), now commonly known as the SAMP and RAMP auxiliaries, respectively (Figure ). Over the years, the SAMP/RAMP method has come to be considered the state-of-the-art approach to asymmetric ketone α-alkylation. In what follows, we provide an overview of the SAMP/RAMP methodology with an emphasis on practical considerations and applications to the stereoselective synthesis of natural products. Several more comprehensive reviews concerning the SAMP/RAMP method are available, and the reader is directed there for additional details.


Tamio Hayashi was born in Gifu, Japan, in 1948

AB - Chemical equations presented. A simple and efficient method for the preparation of β-stereogenic α-keto esters is described using a copper(II)-catalyzed aerobic deacylation of substituted acetoacetate esters. The substrates for the title process arise from catalytic, enantioselective conjugate additions and alkylation reactions of acetoacetate esters. The mild conditions do not induce racemization of the incipient enolizable α-keto ester. The reaction is tolerant of esters, certain ketones, ketals, and nitro groups and utilizes inexpensive, readily available materials.

He graduated from Kyoto University in 1970

The catalytic asymmetric synthesis of a series of tertiary α-aryl cyclopentanones and cyclohexanones has been accomplished via a Pd-catalyzed decarboxylative protonation of the corresponding α-aryl-β-keto allyl esters. Enantioselectivities of up to 92% and 74% were achieved for cyclopentanone and cyclohexanone substrates, respectively. The route described gives access to these important structural motifs in moderate to high levels of enantioselectivity. In particular, this is only the second direct approach for the preparation of tertiary α-aryl cyclopentanones. The synthetic approach allows for simple modification of the aryl group. Significantly, substrates containing sterically hindered aryl groups gave the highest levels of enantioselectivity, and these aryl groups were readily installed by a Pb-mediated arylation of a β-keto allyl ester.