What is asymmetric synthesis in chemistry? | …

Carbon–carbon bond-forming reactions comprise the most important general class of synthetic transformations. Among the various methods used for the construction of these bonds, those based on electrophilic addition to enolates (and their analogs: silyl ketene acetals, silyl enol ethers, enamines, azaenolates, etc.) are especially pervasive. Indeed, enolate chemistry has provided much of the foundation for the advancement of synthetic organic chemistry to its present state. Over the years, an enormous amount of effort has gone into the study of enolate chemistry. Much of this work has focused on the development of strategies for the asymmetric -alkylation of monocarbonyl compounds.

Asymmetric Synthesis | Organic Chemistry Resources …

Asymmetric Synthesis of Letermovir Using a Novel Phase-Transfer-Catalyzed Aza-Michael Reaction

How to synthesis asymetric imine? - ResearchGate

The Evans oxazolidinones are one of the most important types of chiral auxiliary in organic synthesis. They were first reported in 1981 in the context of a diastereoselective aldol addition. The high levels of asymmetric induction associated with their use and the ease of preparation of these auxiliaries are two important reasons why they have become so firmly entrenched in organic synthesis. Oxazolidinones are readily formed by the condensation of chiral, nonracemic 1,2-amino alcohols and a suitable carbonate species (e.g., diethylcarbonate and triphosgene). Once formed, the oxazolidinone (cf. , Scheme ) may be N-acylated by treatment with, for example, n-BuLi and an acid chloride. The resulting N-acyl oxazolidinones (cf. ) have been used in a variety of enolate-based transformations.


The utility of the N-acyl oxazolidinone alkylation has been demonstrated in the context of numerous total syntheses. For instance, in 2003, Evans and Connell used this method in the asymmetric total synthesis of the antifungal macrolide (+)-roxaticin . (+)-Roxaticin is a pentaene macrolide isolated from an unidentified streptomycete similar to Strepfomyces ruber. Like similar compounds, it shows antifungal but not antibacterial activity. In the alkylation step (Scheme ), was treated with TiCl4 and Et3N to provide the required Z-(O)-enolate, which was then treated with BOMCl to afford 209 in 99% yield and >200:1 diastereoselectivity. Removal of the auxiliary was achieved using LiBH4, and the primary alcohol that was produced was oxidized to aldehyde , containing what would ultimately become the C-12 stereogenic center of (+)-roxaticin.

What is ASYMMETRIC SYNTHESIS - Science Dictionary

Asymetric synthesis | Open Library

Synthesis of the SAMP chiral auxiliary can be achieved in six steps, and in 57% overall yield, beginning with (S)-proline using the procedure outlined in Scheme A. An alternative four-step procedure is available (Scheme B); however, it is less desirable as it proceeds through a highly toxic nitrosoamine intermediate . The RAMP auxiliary, on the other hand, may be obtained in six steps and 35% overall yield starting from (R)-glutamic acid (, Scheme C). Purification of each auxiliary is achieved by distillation, and the enantiomeric purity can be established by either optical rotation or by chiral () measurement.

Asymetric Synthesis of Optically Active Polymers with …

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 ,-bisalkylation of ketones possessing both - and '-protons. The Coltart group has employed ACC auxiliaries for the asymmetric synthesis of several biologically important compounds.

Catalytic asymmetric synthesis ..

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 -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 -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.