Acyclic systems reactions

Nucleophilic attack on ring atoms of large heterocycles is largely confined to saturated systems, saturated parts of partially unsaturated systems, and to carbonyl functions and the like. These reactions are not fundamentally different from those of corresponding acyclic systems, except for transannular reactions. 

The intramolecular Michael addition of acyclic systems is often hampered by competing reactions, i.e., aldol condensations. With the proper choice of Michael donor and acceptor, the intramolecular addition provides a route to tram-substituted cyclopentanones, and cyclopentane and cyclohexane derivatives. Representative examples are the cyclizations of /3-oxo ester substituted enones and a,/J-unsaturated esters. 

The participation of sulfoxy groups can be used to control the stereochemistry in acyclic systems. In the reaction shown below, the internal sulfoxide captures the bromonium ion and then undergoes inversion at sulfur in the hydrolytic step. 

The Shapiro reaction has been particularly useful for cyclic ketones, but its scope includes acyclic systems as well. In the case of unsymmetrical acyclic ketones,... 

Fragmentation reactions can also be used to establish stereochemistry of acyclic systems based on stereochemical relationships built into cyclic reactants. In both the examples shown below, the aldehyde group generated by fragmentation was reduced in situ. 

The first example of an intermolecular radical addihon/intermolecular trapping domino reactions of an acyclic system in a stereocontrolled fashion to build stereo-genic centers at the a- and 3-carbons was described by Sibi and coworkers [59]. Enantioselective addition of in-sitw-prepared alkyl radical to crotonate or cinnamate,... 

The versatility of this triafulvene reaction type is demonstrated by the interaction of ally pyridinium betaines 441 and l,2-diphenyl-4,4-diacetyl triafulvene272, which gives rise to fulvenes 565, benzene derivatives 566, or acyclic systems 567 these products are likely to result from an allenic precursor 563 and its isomer 564 originating from a 1,5-H-shift. 

The reaction was applied to an acyclic system for the synthesis of furanoid terpenes (Scheme ll)51. The palladium-catalyzed intramolecular reaction of 47 afforded 48 which was transformed to the target molecule. The latter product was obtained as a 1 1 mixture of marmelo oxide A and B, which is the isomeric mixture found in nature. 

The C-H insertion a to nitrogen can be extended to acyclic systems. The reaction with jY-benzyl-iV-methylamine is an excellent example of the interplay between steric and electronic effects. The benzylic position would be electronically the most activated, but due to the steric crowding, the C-H insertion occurred exclusively at the iV-methyl site (Equation (27)).86 This is a general method for generating a-aryl-/5-amino acid derivatives. The N,N-dimethylamino group undergoes a very favorable C-H insertion by the donor/acceptor-substituted carbenoids. Indeed, the reaction is so favorable that double C-H insertion was readily achieved to form the elaborated -symmetric amine 10 (Equation (28)).87... 

The reactions of allylmetal reagents with carbonyl compounds and imines have been extensively investigated during the last two decades [1], These carbon—carbon bondforming reactions possess an important potential for controlling the stereochemistry in acyclic systems. Allylmetal reagents react with aldehydes and ketones to afford homo-allylic alcohols (Scheme 13.1), which are valuable synthetic intermediates. In particular, the reaction offers a complementary approach to the stereocontrolled aldol process, since the newly formed alkenes may be readily transformed into aldehydes and the operation repeated. 

In acyclic systems the 1,4-relative stereoselectivity was controlled by the stereochemistry of the diene. Thus, oxidation of (E,E)- and (E,Z)-2,4-hexadienes to their corresponding diacetates affords dl (>88% dl) and mesa (>95% me so) 2,5-diacetoxy-3-hexene, respectively. A mechanism involving a t vans-accto xy pal I adation of the conjugated diene to give an intermediate (rr-allyljpalladium complex, followed by either a cis or trans attack by acetate on the allyl group, has been suggested. The cis attack is explained by a cis migration from a (cr-allyl)palladium intermediate. The diacetoxylation reaction was applied to the preparation of a key intermediate for the synthesis of d/-shikimic acid, 3,... 

Use of TMSCl in combination with HMPA, DMAP, or TMEDA all favored 1,2-addition over 1,4-addition. Sequential a-alkoxyalkylcuprate conjugate addition, enolate trapping with TMSCl, and silyl enol ether alkylation provides a one-pot synthesis of tetrahydrofurans (Scheme 3.35) [129]. Cyclic enones afford as-fused tetrahydrofurans, while acyclic systems give complex mixtures of diastereomers. a-Alkoxyalkylcopper reagents also participate in allylic substitution reactions with ammonium salts [127]. 

Intramolecular Diels-Alder (IMDA) is a very powerful reaction, which converts an acyclic system into a bicyclic one, often with high stereocontrol. By positioning a good dienophile (typically in the carboxylic component) and a highly... 

This reaction remains as one of the most reliable transformations to incorporate efficiently a nitrogen atom in cyclic or acyclic systems, providing a powerful synthetic method (Scheme 5). 

The conversion of a nontriazole ring system into a triazole most commonly involves the substitution of a nitrogen for another heteroatom in a five-membered ring. The process usually involves nucleophilic ring opening of the heterocycle followed by ring closure and loss of the other atom. Such reactions thus often involve the same intermediates as those described in the reactions of acyclic systems (Scheme 33). 

The potential of using free radical reactions as synthetic methods will be increased when the origin of selectivity, especially in acyclic systems, is better imderstood [100,101]. 

For the second case, fc, kj we get a new system of reactions a shortened cycle Ai. .. A, A +2. .. A Ai and an "appendix" A,+i A,-. For the new elementary reaction A, A,+2 the reaction rate constant is All other elementary reactions have the same rate constants, as they have in the initial system. After deletion of the limiting step from the "big cycle" A]. .. A, A,+2. .. A A], we get an acyclic system that approximate relaxation of the initial system. 

For example, let us find the asymptotic of left and right eigenvectors for a branched acyclic system of reactions ... 

Let us construct an acyclic system that approximates relaxation of Equation (50) under the same assumption (1) 32 >43- The final auxiliary system after gluing cycles is Ai — A2 — A3 — A2. Let us delete the limiting reaction A3 —> A2 from the cycle. We get an acyclic system A] — A2 — A3. The component A3 is the glued cycle A3— A4— As—> A3. Let us restore this... 

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