Building chiral

The above stereochemical experiments were relatively easy to perform because the natural substrates are chiral. We shall examine two areas in which clever chemistry was required to build chiral substrates. 

Addition of the lithium anion of chloromethylphosphonate to sulfinimine 126 gave a-chloro-P-aminophosphonates 195 in a ratio of 59 41 and 98% total yield.104 The diastereomeric products can be separated and each converted to the corresponding aziridine-2-phosphonates 196, new building chiral blocks for the enantioselective synthesis of a-aminophosphonates 197 and azirinyl phosphonates 198.104... 

Ionization of allylic systems, generating stabilized ions, is one of the most successful methods of inducing cyclization. On treating chiral linalool with protic acids, a 6-exo reaction takes place via a chairlike transition state (concerted mechanism) but the configuration is inverted on building chiral limonene (10)14. 

Multicomponent reactions (MCRs) can be defined as three or more reactants that join together in a single synthetic step to form new products containing portions of all the components. These time and cost-effective reactions are powerful tools that are applicable to combinatorial and parallel syntheses in particular (16-20). However, MCRs for library synthesis are often selected to produce only high quantities of new compounds rather than high quality products (i.e., more diverse and chiral products in pure form). Thus, recent efforts have been made to offset this trend by building chirality into collections of new componnds with the help of efficient stereoselective MCRs (21). 

In terms of zeolites, chiral pores exist only in a low-temperature form of zeolite /3 [112]. Therefore, zeolites are not inherently suitable for either enantiomeric separations or stereospecific catalysis. As noted recently by Ball [6], the development of a new generation of chiral porous material represents one of the major challenges and objectives that faces crystal engineering. Such materials could find widespread application. Furthermore, coordination polymers have the potential to be inherently catalytically active because the metal centers used as nodes could be selected for their known catalytic activity. The issue of how to design and build chiral porous solids is closely related to that of how to design and build polarity into a solid. The subject of polarity is discussed below. 

The low catalyst loading (as low as 0.1mol%) demonstrated the remarkably high catalytic activity of squaramide catalyst 13. This work estabhshed the squaramide unit as an effective scaffold on which to build chiral H-bond donor catalysts. 

Chiral Building Blocks, technical brochure, Lonza AG, Basel, Switzerland, 1991. 

Proteins are the indispensable agents of biological function, and amino acids are the building blocks of proteins. The stunning diversity of the thousands of proteins found in nature arises from the intrinsic properties of only 20 commonly occurring amino acids. These features include (1) the capacity to polymerize, (2) novel acid-base properties, (3) varied structure and chemical functionality in the amino acid side chains, and (4) chirality. This chapter describes each of these properties, laying a foundation for discussions of protein structure (Chapters 5 and 6), enzyme function (Chapters 14-16), and many other subjects in later chapters. 

Cyclitols as novel chiral building blocks in synthesis of heterocyclic natural products 97CC807. 

Dithiane 1-oxide derivatives as chiral auxiliaries and asymmetric building blocks for organic synthesis 980PP145. 

This catalyst was successfully applied to the Diels-Alder reaction of propargyl aldehydes as dienophUes [12] (Scheme 1.21, Table 1.8). Though 2-hutyn-l-al and 2-oc-tyn-l-al are unreactive dienophUes, silyl- and stannyl-suhstituted a,/ -acetylenic aldehydes react with cydopentadiene readily in the presence of 20 mol% of the catalyst at low temperature to give hicyclo[2.2.1]heptadiene derivatives in high optical purity these derivatives are synthetically useful chiral building blocks. 

The reaction has wide scope in respect of the dienophUe / -substituent. The representative less reactive dienophiles, crotonoyl- and cinnamoyl-oxazolidinone, react with cyclopentadiene at -15 °C and 25 °C for 20 h and 24 h giving cycloadducts in 99% ee and 96% ee, respectively. The 3-chloropropenoyl derivative also affords the adduct in high optical purity (96% ee) this adduct is transformed to 2-(methoxycar-bonyl)norbornadiene, a useful chiral building block. Thus, the 3-chloropropenoyl derivative can be regarded as a synthetic equivalent of an acetylene dienophile. 

The need for an overall and combined chemical structure and data search system became clear to us some time ago, and resulted in the decision to build CHIRBASE, a molecular-oriented factual database. The concept utilized in this database approach is related to the importance of molecular interactions in chiral recognition mechanisms. Solely a chemical information system permits the recognition of the molecular key fingerprints given by the new compound among thousands of fingerprints of known compounds available in a database. 

Problem 9.2 I Identify the chirality centers in the following molecules. Build molecular models if i you need help. 

The adjacent iodine and lactone groupings in 16 constitute the structural prerequisite, or retron, for the iodolactonization transform.15 It was anticipated that the action of iodine on unsaturated carboxylic acid 17 would induce iodolactonization16 to give iodo-lactone 16. The cis C20-C21 double bond in 17 provides a convenient opportunity for molecular simplification. In the synthetic direction, a Wittig reaction17 between the nonstabilized phosphorous ylide derived from 19 and aldehyde 18 could result in the formation of cis alkene 17. Enantiomerically pure (/ )-citronellic acid (20) and (+)-/ -hydroxyisobutyric acid (11) are readily available sources of chirality that could be converted in a straightforward manner into optically active building blocks 18 and 19, respectively. 

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