Enantioselective synthesis, definition

Alcohols can be obtained from many other classes of compounds such as alkyl halides, amines, al-kenes, epoxides and carbonyl compounds. The addition of nucleophiles to carbonyl compounds is a versatile and convenient methc for the the preparation of alcohols. Regioselective oxirane ring opening of epoxides by nucleophiles is another important route for the synthesis of alcohols. However, stereospe-cific oxirane ring formation is prerequisite to the use of epoxides in organic synthesis. The chemistry of epoxides has been extensively studied in this decade and the development of the diastereoselective oxidations of alkenic alcohols makes epoxy alcohols with definite configurations readily available. Recently developed asymmetric epoxidation of prochiral allylic alcohols allows the enantioselective synthesis of 2,3-epoxy alcohols. 

We then achieved the enantioselective synthesis of (IS, 3S,lR)-96 as shown in Figure 4.47,82 Evans chiral auxiliary was attached to acid A, giving B. Methylation of B and subsequent hydrolysis of the product afforded C. Acid C was converted to D. Then, intramolecular Diels-Alder reaction of D furnished E. Methylenation of E with Tebbe reagent yielded the desired (15 ,35, 7/ )-96.82 It was shown definitely that only ( S,3S,lR)-96 is bioactive, while other isomers are inactive.83 It must be added that a-himachalene obtained from Himalayan deodar Cedrus deodara possesses the opposite 1 R,1S configuration. Insects and plants sometimes produce similar compounds with different absolute configuration. 

There is also a definite trend towards chirality or enantiopurity in the flavour/fragrance industry, but the reasons for this are somewhat different than for drugs and agrochemicals. There is consumer demand for natural ingredients , produced by natural processes (including fermentation) and preferably involving zero chemical or synthetic steps. Since natural is synonymous with enantiopure, there is a demand for enantioselective synthesis in this industry. 

On the other hand, selective, usually applied to a synthesis, means that of all the possible isomers only one isomer is obtained. However, if the reaction product was/is a mixture of isomers one could speak then of the "degree of selectivity". Since usually one of the isomers will be the predominant isomer, we may say that the reaction (or the synthesis) is selective with respect to this particular isomer. As in the case of "specificity", we may refer to "regioselectivity" or to "stereoselectivity" (either diastereoselectivity or enantioselectivity) and may say, for instance, that a synthesis is 80% diastereoselective. According to the most updated terminology "diastereomers" are all the "stereoisomers" that are not "enantiomers", so geometrical isomers are also included in such a definition. 

Until recently organic photochemistry has only partially focused on stereoselective synthesis, one of the major challenges and research areas in modern organic synthesis. This situation has dramatically changed in the last decade and highly chemo-, regio-, diastereo- as well as enantioselective reactions have been developed. Chemists all over the world became aware of the fascinating synthetic opportunities of electronically excited molecules and definitely this will lead to a new period of prosperity. Photochemical reactions can be performed at low temperatures, in the solid or liquid state or under gas-phase conditions, with spin-selective direct excitation or sensitization, and even multi-photon processes start to enter the synthetic scenery. 

Cohen, F., Overman, L. E. Enantioselective total synthesis of batzelladine F structural revision and stereochemical definition. J. Am. Chem. Soc. 2001, 123, 10782-10783. 

Enantiomeric excess (e.e.) definition, 107 footnote Enantiosdective retro-synthesis, 200-204 Enantioselective syntheses ... 

Cohen, R and Overman, L.E. (2006) Enantioselective total synthesis of batzelladine F and definition of its structure. Journal of the American Chemical Society, 128, 2604—2608. 

To be accurate, the definition should be restricted to asymmetric reactions catalyzed by a combination of l,r-binaphthalene-2,2 -diol (BINOL, 4) and Ti(0 -Pr)4. Nonetheless, this chapter will give some background on non-chiral Lewis acid promoters, and include other asymmetric catalytic systems. We will not discuss the allylations that are promoted by Lewis bases, which are reviewed elsewhere, nor cover the reactions with other electrophiles. Excellent reviews already exist on "Selective Reactions Using Allylic MetaM and Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , as well as in the comprehensive monograph "Modern Carbonyl Chemistry. The use of BINOL-based catalysts in other fields of organic synthesis has also been reviewed. ... 

As initially stated, the definition of multicomponent reaction could be extended also to those reactions that implicate the addition of further reagents only after a suitable time from the very beginning of the procedure. Among others, few Chinese groups reported two notable examples of one-pot Michael addition/Pictet-Spengler cyclization sequence. In particular, in 2011, Zhao et al. developed a high enantioselective organocatalytic synthesis of several... 

L. E. Overman, J. Am. Chem. Soc. 2005, 127, 15652-15658. Total synthesis of (-)-crambidine and definition of the relative configuration of its unique tetracyclic guanidinium core, (c) F. Cohen, L. E. Overman, /. Am. Chem. Soc. 2006, 128, 2594-2604. Evolution of a strategy for the synthesis of structurally complex batzeUadine alkaloids. Enantioselective total synthesis of the proposed structure of batzeUadine F and structural revision. 

Professor Barry M. Trost has provided useful definitions of various kinds of selectivity that apply to nearly all chemical transformations (136). The ideal reaction is perfectly chemoselective ( performs a wanted stractural change and none other ), regioselective ( orients the reacting partners in correct fashion ), diastereoselective ( creates the correct orientations of the various parts of the molecule with respect to each other ), and enantioselective ( enables the formation of a molecule of one-handedness or a mirror image isomer ). None yet meets all of these goals. Considerable challenges and opportunities remain for practitioners of synthesis. 

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