Ring competing side reactions

The first metal-catalyzed [4 +2]-reaction of tethered dienes with 7r-systems was reported by Wender and Jenkins using alkynes initially as the two-carbon component.21 This study was based on the earlier observation by Wender and Ihle that in the [4 + 4]-cycloaddition of bis-dienes a competing side-reaction is the [4 + 2]-cycloaddition of the diene with a mono-ene portion of a second diene. The extension of this reaction to the synthesis of seven-membered rings by trapping the metallacycloheptadiene with CO, a formal [4 + 2 + l]-cycloaddition, has been shown in preliminary studies to be feasible. For example, tethered diene-yne 160 can be converted to cycloheptadienone 163 in an Rh(l)-catalyzed [4 + 2 + l]-reaction with CO, albeit the [4 + 2]- and [2 + 2 + l]-reaction products dominate (Equation (29)). The mechanistic scheme (Scheme 44) illustrates the possible metallacyclic intermediates leading to the observed products and provided the conceptual basis for the realization of three novel reaction types ([4 + 2], [2 + 2 + 1], and [4 + 2 + 1 ]).1... 

Nitronium fluoborate also reacts with silylallenes, as indicated in Eq. 13.40(38], Attack of the electrophile at the allene carbon atom distal to the silicon atom, 1,2-silicon migration and ring closure lead to a silyloxazole. Exposure of this material to bromine in a second step gives 124 in 72% overall yield from 123. This annula-tion is best performed with tert-butyldimethylsilylallenes. With trimethylsilyl compounds, protodesilylation is a competing side reaction. 

In contrast to the asymmetric activation of C—H bonds in benzyl silyl ethers, the dirhodium tetraprolinate, Rh2(5-DOSP)2 (Figure 5.7), was found to be an efficient catalyst in an enantioselective C—H activation of acetals (Scheme 5.16). Interestingly, when the acetals had a methoxy substituent on the aromatic ring, the Stevens rearrangement was a main competing side reaction of the C—H activation of acetals. 

In the lactone acylations discussed above, there was never any evidence for a competing side reaction due to break down of the hemiketal moiety and Michael addition of the alcohol to the newly formed pro-pargylic ketone. This may be taken as filler evidence for the stability of the ketal-alkoxide intermediate however, hemiketal ring opening and intramolecular Michael addition would provide an... 

The competing side reaction is a cyclopropyl anionic ring opening (for a review see ref 13). In the case of isomeric l-benzoyl-2,3-diphenylcyclopropanes, no base-induced isomerization (MeOH/ NaOMe, 65 °C, 4 h) was detected. In many cases these rearrangements require rather drastic conditions but the interconversion can be facilitated by the participation of an adjacent substituent. For example, with an acyl-substituted cyclopropane, enolization permits cisitmns isomerization to proceed without ring opening and therefore without competing anionic structural isomerization. 

Aziridines2 )3-Iodoazides, available by the addition of iodine azide to olefins, undergo reduction of the azide function followed by base-catalyzed ring closure to aziridines. The most satisfactory reagent for this purpose is lithium aluminum hydride, which can accomplish both reaction steps since it is a Lewis acid as well as a reducing agent. Competing side reactions are elimination of the elements... 

As mentioned above, one significant problem with the use of phenyl- or tosylhydrazones in the Shapiro reaction is competing deprotonation of an orfAo-position on the aromatic ring. This side reaction often leads to diminished yields and/or the requirement for >3 equivalents of the alkyllithium base. This problem has been addressed through the use of trisylhydrazones (trisyl = 2,4,6-triisopropylphenyl), which do not contain aromatic protons that are easily metalated.11 For example, trisylhydrazone 15c... 

The direct hydration of Empetal gives only a very poor yield of the desired product because of competing side reactions. These illustrate an important principle in organic chemistry, viz. if an intramolecular reaction can occur to form a 5- or 6-membered ring, then it will usually take precedence over intermolecular reactions. An example in this instance is the intermolecular Prins reaction shown in Figure 3.2. 

However, this difference in reactivity has been used to enforce selectivity in some reactions. For example, Fiirstner has utilized bulky silyl groups to disfavor competing side reactions in the metathesis of trienes (Scheme 2.15). In the absence of a silyl group, considerable quantities of the smaller ring product were obtained. 

It may be noted that reactions involving secondary or primary anions, such as the lithium salts of acetophenone, acetonitrile, or tert-butylacetate, are less efficient. The explanation probably lies in a competing side reaction at the hydrogens a to the ring, which are rendered acidic by complexation. 

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