Enantioselective synthesis stereoselective reactions

With the use of chiral reagents a differentiation of enantiotopic faces is possible, leading to an enantioselective reaction. The stereoselective version of the Michael addition reaction can be a useful tool in organic synthesis, for instance in the synthesis of natural products. 

The focus of Part B is on the closely interrelated topics of reactions and synthesis. In each of the first twelve chapters, we consider a group of related reactions that have been chosen for discussion primarily on the basis of their usefulness in synthesis. For each reaction we present an outline of the mechanism, its regio- and stereochemical characteristics, and information on typical reaction conditions. For the more commonly used reactions, the schemes contain several examples, which may include examples of the reaction in relatively simple molecules and in more complex structures. The goal of these chapters is to develop a fundamental base of knowledge about organic reactions in the context of synthesis. We want to be able to answer questions such as What transformation does a reaction achieve What is the mechanism of the reaction What reagents and reaction conditions are typically used What substances can catalyze the reaction How sensitive is the reaction to other functional groups and the steric environment What factors control the stereoselectivity of the reaction Under what conditions is the reaction enantioselective ... 

Since the formation of optically active, dioxolanone-based di-enolates was not successful, a consecutive alkylation strategy was developed for a short synthesis of (-)-wikstromol (ent-3) from (-)-malic acid (99) (Scheme 25). The first alkylation reaction was analogous to that reported for the enantioselective total synthesis of (-)-meridinol (97). In order to avoid a reduction/re-oxidation sequence and an almost unselective second alkylation, two disadvantages of the synthesis of meridinol (97) [55], we planned to use a different strategy for the second alkylation. Therefore, we have focused our strategy on two stereoselective alkylation reactions, one of dialkyl malates and one of a dioxolanone prepared thereof. Both alkylation reactions were previously described by Seebach and coworker [56, 63, 64]. The... 

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. 

The multitude of hetero Diels-Alder reactions found in the literature clearly demonstrates the importance of this transformation. Thus, this type of cycloaddition is today one of the most important methods for the synthesis of heterocycles. Striking features of this method are the tremendous diversity, excellent efficiency especially in those cases where the reactive dienes and dienophiles are formed in situ, and high stereoselectivity in many cases. There is a broad scope and only little limitation. In recent years the use of Lewis acid, the development of diastereoselective and enantioselective reactions as well as the application of high pressure gave an enormous push. In addition, many of the obtained heterocycles can be transformed into acyclic compounds allowing the stereoselective preparation of e.g. amino and hydroxyl functionalized open chain compounds or even carbocycles to be of interest. Also, for the synthesis of natural products, the hetero Diels-Alder reaction is of great value. Since heterocycles,... 

OXAZOLIDINECARBOXYLATE has previously been described in Volume 70 of Organic Sytheses. An alternative procedure for the preparation of this compound is presented in this volume along with its use in a dia-stereoselective addition reaction with 2-TRIMETHYLSILYLTH1AZOLE to provide a compound bearing a 2-amino-1,3-diol substructure that appears in a variety of natural products. The conversion of abundantly available isosorbide into OSO ISOPROPYLIDENE-l ti-DIANHYDRO-d-GLUCITOL provides a potentially useful carbohydrate-deri ved material for the use in complex tetrahydrofuran synthesis. Finally, asymmetric reduction of an a,j9-unsaturated acylstannane with (R)-BINAL provides access to (S,E)-l-(METHOXYMETHOXY)-l-TRIBUTYLSTANNYL-2-BUTENE, an a-alkoxy allylstannane that has been used in enantioselective vicinal diol synthesis amongst other transformations. 

Dihydropyrones are valuable intermediates for the synthesis of a variety of substituted tetrahydropyran rings. Recently, stereoselective aldol reactions of p-chlorovinyl ketones using the dienol boronate derivative derived from chiral IpC2BOTf was utilized for enantioselective formation of dihydropyrones. No detectable racemization was reported on the cyclization step (eq 4). ... 

Mukaiyama and Kobayashi et al. have developed the use of Sn(OTf)2 in diastereose-lective and enantioselective aldol-type reactions [26,27]. Initially, the stereoselective aldol reactions were performed with a stoichiometric amount of Sn(OTf)2 [28], The reaction between 3-acylthiazolidine-2-thione and 3-phenylpropionaldehyde is a representative example of a diastereoselective syn-aldol synthesis (Eq. 17). 

The selectivity of a chemical reaction is a very important criterion. Besides the chemo- and regioselectivity, the stereoselectivity, i.e. the favored or excluded formation of one or several stereoisomers in the course of a chemical reaction, plays an important role. If there is a formation of (S)- and (K)-enantiomers from a prochiral compound, an enantioselective reaction takes place. What are the reasons for the growing interest in enantioselective reactions and preparation of homochiral compounds Firstly, it is certainly the wish of the chemist to imitate the ability of nature by stereospecific synthesis in the laboratory. Secondly, there are some practical and economic reasons many natural products and a great number of synthetic drugs have a chiral structure and the enantiomers can differ markedly in their biological activity. Sometimes only one of the enantiomers exhibits the wanted optimal activity, while the other is less active or totally inactive, or even toxic. 

Enzymes have high potential in organic synthesis. Applications have been until now mainly based on kinetic resolution, but many opportunities exist to use enzymatic catalysis for enantioselective syntheses. Recently, it was shown by Reetz et al. that a combination of genetic engineering and mutagenesis can easily provide modified enzymes of greatly improved stereoselectivity for the transformation of a given substrate [114]. This concept should find wide applications in catalyzed enantioselective reactions. 

One of the most fascinating aspects in the history of asymmetric catalysis with its countless successful applications in the stereoselective synthesis of a broad variety of functional groups is the structural variety of the complexes which are able to be used as catalysts [1,2]. Many catalysts have been developed based on different ideas and concepts of mechanistic effect. However, in spite of the abundance of such catalysts which have been successfully applied in asymmetric catalysis, not a handful of them possess multifunctional abilities catalyzing different type of enantioselective reactions. The development of such a type of chiral catalyst, the catalytic effect of which is not limited to one reaction but to different types of asymmetric synthetic organic transformations, remained an attractive challenge for a long time. 

The aldol reaction is a versatile method for the construction of new carbon-carbon bonds in a regio-, diastereo-, and enantioselective manner. During the last two decades, major progress toward the total synthesis of macrolide antibiotics was made as a result of the development of the stereoselective aldol reaction in acyclic systems. This section is concerned mainly with the boron-mediated aldol reaction, which is particularly effective for the efficient synthesis of P-hydroxy carbonyl compounds [2]. 

The synthesis of planar-chiral arene chromium complexes has been reviewed several times and has also been discussed in an earlier article [9,10]. Apart from stereoselective complexation reactions, diastereoselective and enantioselective... 

In 2010, Scheldt and coworkers reported cooperative N-heterocyclic car-bene/Lewis acid catalysis for highly stereoselective annulation reactions. This cooperative catalysis process integrating titanium(iv) and triazolium-derived NHCs allowed the synthesis of ds-cyclopentenes 69 with a broad substrate scope and high enantioselectivity (Scheme 20.33). 

Imamoto, T. Yashio, K. Crepy K. V. L. Katagiri, K. Takahashi, H. Kouchi, M. Gridnev ID., P-chiral tetraphosphine dirhodium complex as a catalyst for as5mi-metric hydrogenation Synthesis, structure, enantioselectivity, and mechanism, stereoselective formation of a dirhodium tetrahydride complex and its reaction with methyl (Z)-a-acetamidocinnamate. Organometallics 2006,25,908-914. 

Transition metal-catalyzed allylic substitution reactions with carbon nucleophiles are among the most important carbon-carbon bond formation methods in modem organic synthesis, because of their broad substrate scope under mild reaction conditions. In addition, they are applicable to enantioselective reactions, as well as exhibiting versatility towards the alkene functionality adjacent to the chiral centre for stereoselective derivatization. Tsuji-Trost allylic substitution, involving a (Ti-allyl) metal intermediate, has provided a particular advance in this regard [34, 35]. Most recently, Sawamura et al. [36, 37] have improved the regioselectivity of this reaction with unsymmetrically substituted allylic esters, and thus opened a new approach to sertraline. 

Waldmann and coworkers " (Scheme 7.12) described the enantioselective synthesis of a library of 2,4,6-trisubstituted tetrahydropyrans by an oxa-Diels-Alder reaction. The corresponding pyrane ring is prevalent in a number of natural products. To access it stereoselectively with a solid-phase synthesis strategy, cycloaddition reaction of Danishefsky s diene 59 with resin-bound aldehydes 58 was carried out in the presence of 5 mol% of the chromium catalyst 63. After the release of resin, the product (61) was... 

From an achiral molecule, one enantiomer of the chiral target molecule is formed in an asymmetric reaction, also known as enantioselective reaction. Retrosynthetic analysis considers chiral target molecules as racemates and at this stage does not consider asymmetric synthesis to one enantiomer. When the second stereogenic center in the chiral molecule is introduced in a stereoselective manner, one of two possible diastereomers is formed. Such a synthetic reaction is called diastereose-lective. For the sake of simplicity, during retrosynthetic analysis the formation of diastereomers is not related to the optical purity of the target molecule. This means that starting chiral molecules are considered racemates, which in a diastereoselec-tive step affords one of the two possible racemic products. 

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