Regioselective transformations

As outlined above, enantioconvergent processes require two separate reaction pathways in order to transform a racemic substrate into a single product enantiomer. This is accomplished by employing a catalyst, which transforms one of the substrate enantiomers to the product with retention of configuration. Concurrently, another catalyst, with opposite enantioselectivity and opposite regioselectivity, transforms the other substrate enantiomer with inversion of configuration (Figure 5.24). 

Biocatalysis has long been known as a green technology, capable of delivering highly stereo-, chemo- and regioselective transformations that can sometimes allow... 

Several building blocks were prepared separately (Chart 7). Methyl frans-cinnamate gave by Sharpless enantiocontrolled dihydroxylation a diol from which by a series of stereo- and regioselective transformations (96) and Ru-catalyzed oxidation for transformation of the phenyl into a carboxyl group accompanied by adequate protection (97) and deprotection steps the protected OHAsp derivative 98 was obtained. 

Recent developments in the enzymatic synthesis of carbohydrates can be classified into four approaches 1) asymmetric C-C bond formation catalyzed by aldolases (1-10 2) enzymatic synthesis of carbohydrate synthons (loll) 3) asymmetric glycosidic formation catalyzed by glycosidases (12.-17) and glycosyl transferases (18-23.) and 4) regioselective transformations of sugars and derivatives (24-25). These enzymatic transformations are stereoselective and carried out under mild conditions with minimum protection of functional groups. They hold promise in preparative carbohydrate synthesis. In connection with this book, we focus on the first two approaches. 

Treatment of l,3-dihalo-2-propyl and 2,3-dichloropropyl A7-arylcarbamates 11 and 14 with ammonium fluoride results in the regioselective transformation to the 2(3f/)-oxazolones 12 and 15 or to the exocyclic methylene derivatives 13 and 16 depending on the temperature (Fig. 5.5). ... 

Direct and regioselective transformation of oxaspirohexanes into cyclopentanones is best achieved with lithium iodide.69 Mechanistically, this isomerization occurs via initial opening of the epoxide ring by nucleophilic addition of lithium iodide and is followed by regioselective migration of the more substituted carbon atom of the cyclobutane ring.69-73... 

Non-anomeric positions can be regioselectively transformed by radical substitutions of halosugars or sulfur derivatives to yield mainly C-branched sugars by creation of new C-C bonds. 

Addition of diazomethane to a toluene solution of C70 generated a 12 1 2 mixture of pyrazolines. The structures of the three isomers are shown in Scheme 65. The formation of 174a and 174b in unequal amounts appears to be a well-characterized regioselective transformation at a fullerene bond. Photolysis and ther-... 

In order to facilitate the desired palladium-catalyzed creation of the welwistatin C4-C11 bond, compound 70 was regioselectively transformed into /3-kclocslcr 65 by treatment with LDA in the presence of HMPA, followed by addition of Mander s reagent. The crucial palladium-catalyzed crosscoupling reaction took place in the presence of palladium acetate, th-tert-butylphosphine and potassium ferf-butoxide, and afforded compound 64, which contains the complete welwistatin skeleton. The installation of a nitro-... 

Even more striking is the regioselective transformation of the highly structured toluene n-complex, with bromine situated specifically over the ortho and para positions to afford the same isomeric (product) mixture of o- and p-bromotoluenes as that obtained in solution [63]. As close as these pre-equilibrium intermediates are structurally akin to the (ordered) transition states for electrophilic bromination, it is important to emphasize that they are formed essentially upon bimolecular collision with no activation energy, and the donor/acceptor binding is in accord with the Mulliken formulation. 

A regioselective transformation of quinolines to indoles was developed. The 1,4-dihydro Meisenheimer salts were prepared, to the exclusion of the 1,2-isomer. Yields were poor to excellent <03TL6241>. 

In this chapter, methods for oxidation, reduction, and deoxygenation of carbohydrates are presented. In most cases, the reactions have been used on aldoses and their derivatives including glycosides, uronic acids, glycals, and other unsaturated monosaccharides. A number of reactions have also been applied to aldonolactones. The methods include both chemical and enzymatic procedures and some of these can be applied for regioselective transformation of unprotected or partially protected carbohydrates. 

Bordoloi, M. Cadmium chloride-magnesium-water a new system for regioselective transformation of conjugated nitroalkenes to ketocompounds conversion of 6-nitro-D5-steroids to 6-ketosteroids. J. Chem. Soc., Chem. Commun. 1993, 922-923. 

Das, N. B., Sarangi, C., Nanda, B., Nayak, A., Sharma, R. P. SnCl2.2H20-Mg-H20 a mild reagent system for the regioselective transformation of conjugated nitroalkenes to carbonyl compounds. J. Chem. Res., Synop. 1996, 28-29. 

In case of five-membered rings, allylic-substituted double bonds can also undergo cyclization, which allows the regioselective transformation of an unsymmetric triene involving two consecutive carbocyclizations followed by a silylation step (22) [73],... 

As mentioned in Sect. 3.2, the carbon-carbon triple bond has a superior reactivity in hydrosilylation compared to a double bond, presumably due to a faster insertion step. This creates an opportunity to perform regio- and chemoselective transformations of enynes [68]. Regioselective transformations of 1,6- and 1,7-enynes proceed via preferred insertion of the triple bond (24). 

Strained cage compounds can be made by intramolecular photocycloaddition of properly designed ene/enone substrates. In an interesting example from J. R. Scheffer, a ben-zoquinone derived Diels-Alder product is regioselectively transformed into a (halO cage compound. This is a more complicated version of the classical intramolecular photochemical cyclization reactions of benzoquinone derivatives (for example see B. Pandey s cage synthesis from a naphthoquinone-cyclopentadiene in Chapter 3). 

It was known in the early 70 s that unsymmetrically substituted anhydrides and im-ides can undergo highly regioselective transformations, e.g. to lactones and lactams, respectively (see Scheme 6.23) [166]. The growing importance of such products as synthetic intermediates raised the issue of control of regioselectivity, and several authors attempted to identify the factors at play [167-169]. The emphasis was on metal hydride reductions of succinic anhydrides to y-lactones, and succinimides to hydroxypyrrolidinones. Suess [167], Rosenfield and Dunitz [47], and independently Kayser and Morand [169], proposed that the approach of a nucleophile to the less substituted carbonyl group can actually be more hindered if there is indeed a strong preference for rearside attack. The two pathways are compared in Scheme 6.24. 

The presence of halogen X (X = F, Cl, Br, or 1) in the molecule of trifluoromethylated heterocycle opens an additional possibility for further regioselective transformations. Functiolization of these materials can be achieved using metal-halogen exchange (for X = Cl, Br, or 1) followed by the reaction of lithiated intermediate with different electrophiles." ... 

Preparations of A-aminoepimines and their catalytic reduction by hydrazine over Raney nickel have been described by Paulsen and Stoye. Using 5,6-di-(9-mesyl derivatives of 1,2-isopropylidene-ot-D-gluco-, ot-D-allo-, and ot-D-gulofura-nose (410-412), and compound 419, reactions with anhydrous hydrazine afforded the corresponding A-aminoepimines 413-415, and 420, which were regioselectively transformed into 5-amino-5,6-dideoxy derivatives 416-418, and 421. 

Treatment of MBH addcut 1 with carboxylic adds under Mitsunobu conditions gave almost exclusively the S 2 products 4, rather than S 2 product 5. Weak and bulky carboxylic acids and low temperatiues favor S 2 addition. Although the reaction conditions were effective for alkyl substituted derivatives, the addition of EtsN to the Mitsunobu conditions was necessary to improve the 5n2 S 2 ratios for the vinyl and phenyl derivatives (Scheme 3.3). " More recently, it was found that the nucleophilic substitution reaction mediated by triphenylphosphine linked to non-crosslinked polystyrene 6 led to a significantly more regioselective transformation. Tri-substituted alkenes 4 were obtained almost quantitatively via a highly regioselective 5n2 Mitsunobu reaction (Scheme 3.3). ... 

This chapter documents advances in the use of catalysis for regioselective transformations of carbohydrate derivatives. For this discussion, the catalysts are grouped into broad structural or functional classes (Lewis bases, Brpnsted acids, Lewis acids, transition metals). Processes that make use of enzyme catalysis (chemoenzymatic methods or metaboUc engineering) are not discussed here [8-10]. Emphasis is placed oti recent results that were not discussed in previous reviews on this and related topics [11—13]. 

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