Pummerer cyclization

Acetalization or ketalization with silylated glycols or 1,3-propanediols and the formation of thioketals by use of silylated 1,2-ethylenedithiols and silylated 2-mer-captoethylamines have already been discussed in Sections 5.1.1 and 5.1.5. For cyclizations of ketones such as cyclohexanone or of benzaldehyde dimethyl acetal 121 with co-silyl oxyallyltrimethylsilanes 640 to form unsaturated spiro ethers 642 and substituted tetrahydrofurans such as 647, see also Section 5.1.4. (cf. also the reaction of 654 to give 655 in Section 5.2) Likewise, Sila-Pummerer cyclizations have been discussed in Chapter 8 (Schemes 8.17-8.20). 

Finally, saturated oxazolo[3,2-tf]pyridine derivatives can also be accessed via a Pummerer cyclization-deprotona-tion-cycloaddition cascade from imidosulfoxides <1999JOC2038> or by a [3+2] cycloaddition of nonstabilized... 

Pummerer reaction conditions was followed by cycUzation to isomilnchnone 292 and hence to cycloadduct 293, which loses water to form a-pyridone 294. Subsequent manipulation involving deoxygenation and debenzylation completed the synthesis. In similar fashion, the azaanthraquinone alkaloid dielsiquinone was synthesized for the first time. Also, the quinolizidine alkaloids ( )-lupinine and ( )-anagyrine, and the ergot alkaloid ( )-costaclavine were synthesized using this Pummerer cyclization-cycloaddition cascade of imidosulfoxides and isomiinch-nones. 

Pummerer cyclization. Pummerer rearrangement of 4-(phenylsulfinyl)butyric acids (1) catalyzed by TsOH results in 4-phenylthio-4-butanolides (2). Oxidation followed by thermolysis results in either 3 or 4, depending on the substitution pattern. 

The asymmetric version of an intramolecular Pummerer-type cyclization is quite useful for the synthesis of optically active heterocyclic compounds. Only a few examples of these types of reactions have been reported, and the ee yields were low. An example of an asymmetric intramolecular Pummerer cyclization was reported... 

The mechanism of penicillin biosynthesis from the Arnstein tripeptide, 8-(L-a-aminoadipoyl)-L-cysteinyl-D-valine (ACV), has been extensively studied and reviewed by many chemists. Most of the biosynthetic mechanisms have been ascertained by Baldwin and Bradley using an excellent enzymatic technique.55 However, the first step in the biosynthesis of penicillin, conversion of the Arnstein tripeptide to a cis-P-lactam intermediate, is still a fascinating mechanistic problem. Although Baldwin et al. recently proposed a mechanism involving an iron-bound thioaldehyde formation route via a Pummerer-type cyclization, the intermediate for this mechanism has not been identified. The mechanism of selective formation of the cw-P-lactam ring is still also unknown (Fig. 39).56 These types of biomimetic reactions have been chemically studied. An example of an unsuccessful intramolecular Pummerer cyclization of the sulfoxide involving a cysteine moiety under standard Pummerer conditions was reported by Wolfe et al.57 Although Kaneko reported the conversion of the very simple 3-phenylsulfinyl propionamide into a P-lactam with TMSOTf/triethylamine,58 a successful biomimetic synthesis of... 

McAllister, L. A., Brand, S., de Gentile, R., Procter, D. J. The first Pummerer cyclizations on solid phase. Convenient construction of oxindoles enabled by a sulfur-link to resin. Chem. Commun. 2003, 2380-2381. 

Scheme 1 Possible mechanisms for the Pummerer cyclization to form spiro-indolenines...

The Mizoroki-Heck reaction promoted by microwave irradiation was first described by Laihed and Hallberg [205]. For easy catalyst recovery, solid-supported systems were often used. An a-heteroatom-substituted carbonyl linker has been utilized in solid-phase approaches to oxinolines by Pummerer cyclization [206]. The reaction performed with s/c = 20 in the presence of phosphine ligands (ratio ligand/palladium-precursor = 1 1) in 88-99% yield at 7 h reaction time. 

Procter and coworkers also applied their connective Pummerer methodology to the total synthesis of the fused-ring alkaloid cryptotackieine (neocryptolepine). To this end, they followed the S5mthetic route shown in Scheme 20.3S. which includes a connective Pummerer cyclization from 179 followed by a p5a idine-forming reaction sequence mediated by samarium, also developed by the Procter group. 

Pummerer cyclization of sulfoxide 109. Several reaction conditions were attempted, including the use of different electrophiles (trifluoroacetic anhydride, jo-TsOH) and bases. Eventually, the desired reaction took place in good yield with the use of TMSOTf and an excess of Hunig s base. 

Synthesis of Oxindoles Using Samarium(II) Iodide for Sulfone Cleavage. a-Sulfanyl-A-aryl acetamide attached to resin via the sulfur atom 134 undergoes efficient Pummerer cyclization upon activation of sulfur group to yield oxindole derivatives 135 (Scheme 12.30). Oxidation of 135 to sulfone 136 using Oxone followed by alkylation yielded the alkylated sulfone 137, which was then cleaved from the resin in a traceless manner using samarium(ll) iodide to yield the heterocyclic product 138. 

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