Regioselective reactions

Other interesting regioselective reactions are carried out within the synthesis of nitrofurantoin. Benzaidehyde semicarbazone substitutes chlorine in chloroacetic ester with the most nucleophilic hydrazone nitrogen atom. Transamidation of the ester occurs with the di-protic outer nitrogen atom. Only one nucleophilic nitrogen atom remains in the cyclization product and reacts exclusively with carbonyl compounds. 

When N,A/ -dimethyl-Af,N -diphenyl-p-phenylenediamine (231) underwent irradiation in die presence of oxygen, a remarkably regioselective reaction was observed, from which the /V,A/ -dimediylindolo[2,3-f ]carbazole (190) was obtained, without coformation of die other possible isomeric product, indolo[3,2-/)]carbazole (4). The expected intermediate 232, where only one ring closure had taken place, could not be detected. The authors attributed this fact to a two-photon autosensitization mechanism in which die conversion of 231 into 190 is sensitized by 232, permitting accumulation of 232 only in extremely small concentrations (83JA6268). 

The hydroboration is a regioselective reaction. In general the addition will lead to a product, where the boron is connected to the less substituted or less sterically hindered carbon center. If the olefinic carbons do not differ much in reactivity or their sterical environment, the regioselectivity may be low. It can be enhanced by use of a less reactive alkylborane—e.g. disiamylborane 8 ... 

With an unsymmetrical ketone as CH-acidic substrate, two regioisomeric products can be formed. A regioselective reaction may in such cases be achieved by employing a preformed iminium salt instead of formaldehyde and ammonia. An iminium salt reagent—the Eschenmoser salt—has also found application in Mannich reactions. ... 

However, in these reactions, over-degradated product is also formed, and it is necessary to develop methods to inhibit the unnecessary reaction to afford a single product in high chemical yield. Stereo- and regioselective reactions are also desired. 

Enzymes are proteins catalyzing all in vivo biological reactions. Enzymatic catalysis can also be utilized for in vitro reactions of not only natural substrates but some unnatural ones. Typical characteristics of enzyme catalysis are high catalytic activity, large rate acceleration of reactions under mild reaction conditions, high selectivities of substrates and reaction modes, and no formation of byproducts, in comparison with those of chemical catalysts. In the field of organic synthetic chemistry, enzymes have been powerful catalysts for stereo- and regioselective reactions to produce useful intermediates and end-products such as medicines and liquid crystals. ... 

Regioselective reactions belong to the most important applications of homogeneous catalysis. An example is the hydroformylation of alkenes, which is a very important industrial reaction ... 

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markovnikov rule. Internal alkynes give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to (3-acetoxy- or (3-methoxyalkenylmercury intermediates,152 which can be reduced or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate that is opened by nucleophilic attack at the more positive carbon, that is, the additions follow the Markovnikov rule. Scheme 4.8 gives some examples of alkyne hydration reactions. 

Chloro-3-(5-chloropyrazol-3-yl)quinoxaline (137, R = H) gave mainly 2-(2-acetyl-5-chloropyrazol-3-yl)-3-chloroquinoxaline (137, R = Ac) [neat Ac20, reflux, 7 min, then 20°C, 30 min 86% (after separation from a little of the 1-acetyl isomer) structure confirmed by X-ray analysis] or mainly 2-(l-acetyl-5-chloropyrazol-3-yl)-3-chloroquinoxaline [neat Ac20, 80°C, 2 min ( ), then 20°C, 12 h 70% (after separation from the 2-acetyl isomer)] an extraordinary pair of regioselective reactions.495... 

Cycloadduct 30a underwent an easy cleavage of the sulfur-carbon bond by attack of alcohols to give ring-opening products 31 and 32, the latter as inseparable diastereomeric mixtures (see Equation (6) and Table 3) <1997T4611>. A completely regioselective reaction was observed with bulky alcohols resulting in the exclusive formation of 31 (see entries 3 and 4). 

The microwave-assisted dipolar cycloaddition of pyridazinyl quaternary salts such as 20 was shown to be substantially better than the reaction using conventional heating. Novel regioselective reactions using monosubstituted dipolarophiles were also included <06SL804>. 

Bromination can exhibit stereo-, regio- and chemo-selectivity when the reaction is carried out in the presence of nucleophiles (solvent or added salt). When the ionic intermediate is a bromonium ion, a stereospecific but non-regioselective reaction is expected. In contrast, for an open bromo-carbocation, the products should be formed regioselectively but not stereo-specifically. These considerations were understood very early since, in fact, Roberts and Kimball (1937) suggested bridged ions as bromination inter-... 

The use of a nitrogen nucleophile in the side chain (as an amide) also leads to an intramolecular 1,4-addition under the standard conditions for the palladium-catalyzed 1,4-oxidation reactions52. Nitrogen nucleophiles employed for this reaction comprise tosy-lamides, carboxamides, carbamates and ureas. The reactions are run in acetone-acetic acid with p-benzoquinone (BQ) as the oxidant. In most cases highly stereo- and regioselective reactions were obtained and some examples are given in Table 3. 

Cyclization of y-alkenyloximes (109) and (110) proceeds with strong electrophilic phenyl- selenating agents (293-295). This regioselective reaction provides the formation of (phenylseleno)methylsubstituted 1,2-oxazines (111) and... 

A key reaction in the formal total synthesis of (-)-mycalamide A involved the intermolecular ruthenium-catalyzed Alder-ene reaction between 157 and 158 to give the dienoate 159 (Scheme 35).94 This regioselective reaction provided a 63% yield of 159, which was subsequently transformed to a key building block 160 which was taken on to (-)-mycalamide A. 

The regiochemistry can be controlled by the nature of the substituents. With a tri-methylsilyl-substituted acetylene, the trimethylsilyl groups are placed in a positions of zirconacyclopentadienes with excellent selectivity (Eq. 2.8) [20]. With a phenyl-substituted alkyne, regioselective reactions are usually observed, although in some cases a mixture of two isomers may be formed. 

To summarize, electrophilic substitutions and metalations of thiophenes take place preferably at the a-positions due to the electronegativity of the sulfur atom. This is the consequence of the more effective incorporation of lone pair electrons on the sulfur into the aromatic system. Although regioselective reactions are routinely performed for oc,p-dihalofurans, regioselectivity is not as easily achieved in Pd-mediated chemistry with oc,p-dihalothiophenes. 

Diketones. Some years ago Heiba and Dessau reported that Mn(OAc), promotes oxidative addition of isopropenyl acetate to ketones to give 1,4-diketones in 20-35% yield (6, 356). Use of CAN as the oxidant results in higher yields (65-80%) and a regioselective reaction at the more substituted a-position of the ketone.1 Use of vinyl acetate results in the dimethyl acetal of 4-oxo aldehydes. 

The 1,3,2-dioxastannolanes are important in organic synthesis because they can readily be derived from dialkyltin oxide and 1,2-diols, as in carbohydrates the reaction can be carried out in toluene in a few minutes under microwave irradiation.387 The dioxastannolanes can then be subjected to regioselective reaction with an electrophile such as an acyl chloride (Equation (140)) or sulfonyl chloride, or an isocyanate. The acylation or sulfonation can be carried out with catalytic amounts of the dialkyltin oxide, including the recoverable (C6F13CH2CH2)2Sn0.388... 

The 1,5-substitution of l-chloro-2-en-4-ynes with Grignard reagents has been described by Dulcere and co-workers [41] but lacks generality with regard to the nucleophile (see Section 2.3). In contrast, the regioselective reaction of enyne acetates 47 with various lithium cuprates proceeds smoothly in diethyl ether, furnishing exclusively vinylallenes 48 with variable substituent patterns (Scheme 2.17) [42],... 

Addition of (TMS)3SiH to a-chiral ( )-alkene 7 was found to take place with a complete Michael-type regioselectivity (Reaction 5.8) [26]. A complete syn stereoselectivity was observed for R = Me, and it was rationalized in terms of Felkin-Ahn transition state 8, which favours the syn product similar to nucleophilic addition. 

Zimmerman and Hoffacker also observed a regioselective reaction subjecting various aryl-substituted 1,4-pentadienes to photoinduced electron transfer using DCN and DCA. The radical cations produced underwent a regioselective cyclization wherein one electron-deficient aryl group of one diarylvinyl moiety bonds to the (3-carbon of the second diarylvinyl group (Scheme 30) [41]. 

Regioselective Reactions of JV-Pyridinium Salts with Organometallic Reagents... 

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