Systems regioselectivity

Acyl group migration can be effected photochemically in nitrogen-containing systems. Regioselective photo-Fries rearrangements in 5- and 6-acetoxyindoles have been observed in... 

As predicted by retrosynthesis, isoxazole formation proceeds via (isolable) intermediates 10 and 11. In the case of unsymmetrically substituted P-dicarbonyl systems, regioselectivity can be controlled by utilizing different carbonyl electrophilicities and observing defined reaction conditions. 

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

In principle, the direct hydride addition or catalytic hydrogenation, which did not give chlorins, was replaced by an electrocyclic intramolecular addition which is much easier with the above system. Complete regioselectivity was also achieved since electrocyclization did not occur with the resonance-stabilized ring C. 

The high regioselectivity ( stereoelectronic control ) in the ring cleavage by chlorination of sulfur was anticipated. It had been found before that in corresponding bicyclic systems such as in the scheme below oxidation of the sulfur atom always led to the undesired cleavage of the S—Cg bond. This was rationalized through the observation on molecular models that... 

In contrast to oxidation in water, it has been found that 1-alkenes are directly oxidized with molecular oxygen in anhydrous, aprotic solvents, when a catalyst system of PdCl2(MeCN)2 and CuCl is used together with HMPA. In the absence of HMPA, no reaction takes place(100]. In the oxidation of 1-decene, the Oj uptake correlates with the amount of 2-decanone formed, and up to 0.5 mol of O2 is consumed for the production of 1 mol of the ketone. This result shows that both O atoms of molecular oxygen are incorporated into the product, and a bimetallic Pd(II) hydroperoxide coupled with a Cu salt is involved in oxidation of this type, and that the well known redox catalysis of PdXi and CuX is not always operalive[10 ]. The oxidation under anhydrous conditions is unique in terms of the regioselective formation of aldehyde 59 from X-allyl-A -methylbenzamide (58), whereas the use of aqueous DME results in the predominant formation of the methyl ketone 60. Similar results are obtained with allylic acetates and allylic carbonates[102]. The complete reversal of the regioselectivity in PdCli-catalyzed oxidation of alkenes is remarkable. 

Furthermore, the regioselective hydrogenolysis can be extended to internal allylic systems. In this case, clean differentiation of a tertiary carbon from a secondary carbon in an allylic system is a problem. The regioselectivity in the hydrogenolysis of unsymmetrically substituted internal allylic compounds depends on the nature and size of the substituents. The less substituted alkene 596 was obtained from 595 as the main product, but the selectivity was only... 

The same regioselective and stereospecific reactions are observed in decalin systems. The 3/3-formate 605 is converted into the a-oriented (j-allylpalladium complex 606, and the hydride transfer generates the fra .s-decalin 607, while the cis junction in 610 is generated from the 3tt-formate 608 by attack of the hydride from the /3-side (609). An active catalyst for the reaction is prepared by mixing Pd(OAc)2 and BU3P in a 1 I ratio with this catalyst the reaction proceeds at room temperature. The reaction proceeded in boiling dioxane when a catalyst prepared from Pd(OAc)2 and BujP in a 1 4 ratio was used[390]. 

Desulfonylation of equally substituted allylic sulfones with NaBH4 and LiBHEt3 usually yields a mixture of regioisomeric alkenes[406,407]. However, the regioselective attack of the less substituted side of the unsymme-trically substituted allylic system with LiEtjBH has been utilized for the removal of the allylic sulfone group in synthesis of the polyprenoid 658[408],... 

Elimination is typically regioselective and gives a conjugated diene rather than an isolated or cumulated diene system of double bonds... 

In the case of the 2-dimethylamino- (or 2-amino-)methylene derivatives, the products were at first thought to be pyrimido[4,5-c]isoquinolines (267), but later work with 6-(N-substituted amino)uracils assigned the structures of the products (268) as belonging to the isomeric pyrimido[4,5-f>]quinoline system (74CB2537), in agreement with the regioselection rules above. 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

When both the 1,3-dipoIe and the dipolarophile are unsymmetrical, there are two possible orientations for addition. Both steric and electronic factors play a role in determining the regioselectivity of the addition. The most generally satisfactory interpretation of the regiochemistry of dipolar cycloadditions is based on frontier orbital concepts. As with the Diels-Alder reaction, the most favorable orientation is that which involves complementary interaction between the frontier orbitals of the 1,3-dipole and the dipolarophile. Although most dipolar cycloadditions are of the type in which the LUMO of the dipolarophile interacts with the HOMO of the 1,3-dipole, there are a significant number of systems in which the relationship is reversed. There are also some in which the two possible HOMO-LUMO interactions are of comparable magnitude. 

Diethylamino-4-(4-methoxyphenyl)-isothiazole 5,5-dioxide 6 is (95T(51)2455) a highly reactive partner in 1,3-dipolar cycloadditions with several dipoles. Azomethine yhdes, such as oxazolones 7 and miinchnones 8, afforded with 6 bicychc pyrrolo[3,4-d]isothiazole 5,5-dioxides 9, 10, 11 in satisfactory yield. The regioselectivity of the reaction was excellent. The thermal behavior of these new bicychc systems was investigated. When heated at their melting point or shghtly above, triarylpyrroles 12, 13 were obtained through SOj and AtiV-diethylcyanamide ehmination. 

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