Base-Promoted Rearrangements

The synthesis was carried out as shown in Scheme 13.24. A diol was formed and selectively tosylated at the secondary hydroxy group (Step A-4). Base then promoted the skeletal rearrangement in Step B-l by a pinacol rearrangement corresponding to 23-11 => 23-III in the retrosynthesis. The key intramolecular Michael addition was accomplished using triethylamine under high-temperature conditions. 

D. This product was not stereochemically characterized, and need not be, because the stereochemically important site at C-l can be epimerized under the basic cyclization conditions. Thus, the equilibration of the ring junction through a dienol can allow the cyclization to proceed to completion from either stereoisomer. Step C is the pinacol rearrangement corresponding to II => III in the retrosynthesis. A diol is formed and selectively tosylated at the secondary hydroxyl group (step B). Base then promotes the... 

This chapter includes examples of aliphatic nucleophilic substitution at both sp and sp centers, aromatic nucleophilic substitution, E2 elimination, nucleophilic addition to carbonyl compounds, 1,4-addition to a, -unsaturated carbonyl compounds, and rearrangements promoted by base. 

The ring contraction was surprisingly successful.11 The best yields of 81 were with sodium bicarbonate though KOH can be used. Presumably only one ketone is necessary 87 for even such a weak base to promote the rearrangement from the monohydrate 88. Under the reaction conditions the product is the stable carboxylate anion 90. 

Pyridine is a sufficiently strong base to promote reaction, but alkoxide ions are more commonly employed. The reaction proceeds by way of an azirine intermediate 41, which has been isolated in some instances79. Usually, however, this undergoes direct transformation to the a-aminoketone. The rearrangement has been little studied since the last review... 

Other synthetic applications of the phosphazene bases include the use of Bu -Pl (37) in the alkylation of adenine in solution or solid phase, and the catalytic esterification of various glycerol derivatives with fatty methyl esters at room temperature. On occasions, the action of the phosphazene bases may promote processes that other proton abstractors do not, such as the observed rearrangement of (43) to the flavone (44) in the presence of (40e) (OBn = benzoyloxy). Patented process, include the purification " and assembly of polyhedral oligomeric silsesquioxane monomers, and the catalytic activation of silylated nucleophiles. ... 

Rearrangements Promoted by Substitution, syn-anti Proton site exchan in [Pd(A -allyl)(diphos)]X (X = PFg or BF4 A -allyl may be substituted) is accelerated by an added base such as pyridine. The results indicate an 5 n2 substitution process as in Scheme 4 and not an allyl rotation as previously proposed. In comparison, syn-syn and simultaneous anti-anti site exchange... 

Apart from the Cope and Claisen-Cope rearrangements, a number of named reactions are to be found within the category of [3,3] shifts t reactions (6.106)-(6.111) are examples of some of these processes. The thio-Claisen rearrangement the sulphur analogue of reactions (6.106) and (6.107) is also well known. The all carbon atom counterpart of the Claisen rearrangement ((6.106) 0=CH2) was not discovered until it was realized that the final aro-matization step required the presence of a strong base to promote the necessary tautomeric change. In reactions (6.1 07)-(6.111) the influence of steric factors on the stereoselectivity of the reactions is apparent. In reaction (6.109),... 

Nitroethylfurazan 143 has been synthesized by base-promoted mononuclear heterocyclic rearrangement (MHR) of oxime 142 (Scheme 82) (36G819,82G181). 

An important improvement in the oxy-Cope reaction was made when it was found that the reaction is strongly catalyzed by base.212 When the C(3) hydroxy group is converted to its alkoxide, the reaction is accelerated by a factor of 1010-1017. These base-catalyzed reactions are called anionic oxy-Cope rearrangements, and their rates depend on the degree of cation coordination at the oxy anion. The reactivity trend is K+ > Na+ > Li+. Catalytic amounts of tetra-rc-butylammonium salts lead to accelerated rates in some cases. This presumably results from the dissociation of less reactive ion pair species promoted by the tetra-rc-butylammonium ion.213... 

The preparation and the base-promoted Smiles rearrangement of phenylfuroxans bearing 2-hydroxyethylthio, 2-hydroxyethylsulfonyl, carbamoylmethylthio, and carbamoylmethylsulfonyl functions at the heterocyclic ring have been described. The rearrangement was also investigated in related furazans (1,2,5-oxadiazoles) for comparison <2001J(P1)1751>. 

The skeletal rearrangements are cycloisomerization processes which involve carbon-carbon bond cleavage. These reactions have witnessed a tremendous development in the last decade, and this chemistry has been recently reviewed.283 This section will be devoted to 7T-Lewis acid-catalyzed processes and will not deal, for instance, with genuine enyne metathesis processes involving carbene complex-catalyzed processes pioneered by Katz284 and intensely used nowadays with Ru-based catalysts.285 By the catalysis of 7r-Lewis acids, all these reactions generally start with a metal-promoted electrophilic activation of the alkyne moiety, a process well known for organoplatinum... 

When neighboring-group participation is a feature of the glycosylation reaction, the use of a base in this manner frequently results in the isolation of orthoesters rather than the desired glycosides. In the case of activation by triflic anhydride, it is possible to avoid this problem by simply omitting the base. Alternatively, with more sensitive substrates, the hindered base may be retained and boron trifluoride ethe-rate be added to promote the rearrangement of the orthoester to the glycoside, as in... 

Three-component assembly of allenes, organic halides and arylboronic acids has been reported in which Suzuki coupling of a Jt-allylpalladium complex with an orga-noboronic acid is utilized (Scheme 16.26) [31], Addition of phosphorus ligands to the reaction mixture greatly decreases either the product yields or E/Z ratios. The decrease in E/Z ratio may be explained based on the fact that donor ligands readily promote anti-syn rearrangement of a Jt-allylpalladium species via a cr-allylpalladium intermediate. 

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