Thionium ions generated using

Non-nucleophilic activating agents, such as p-toluenesulfonic acid, are generally used to generate the intermediate thionium ions. The use of trifluoroacetic anhydride in the Pummerer step of the kopsanone synthesis is feasible, since at elevated temperatures an equilibrium is established between the thionium ion and trifluoroacetoxy sulfide intermediates. Trifluoroacetic anhydride in combination with a Lewis acid can also be used. Under these latter conditions efficient intermolecular reactions of acylthionium ions with aromatic systems are observed. ... 

As mentioned in Section 10.1.2, Padwa and co-workers (40,41) employed the Pummerer reaction to generate and trap isomtinchnones. This group (190,191) has now adapted the intramolecular version of this tactic to the synthesis of several alkaloids of the pyridine, quinolizidine, and clavine classes. In each case, a 2-pyridone serves as the keystone intermediate. For example, Kuethe and Padwa (190) employed this Pummerer reaction of imidosulfoxides that contain tethered iz-bonds in a formal synthesis of the frog alkaloid ( )-pumiliotoxin C. They also used this methodology to synthesize the azafluorenone alkaloid onychine (295) (Scheme 10.42) (191). Generation of the thionium ion 291 under standard... 

The total synthesis of (+)-deethylibophyiiidine was achieved by J. Bonjoch et ai. using a tandem Pummerer rearrangement/thionium ion cyclization to generate the quaternary spiro center.The suifoxide was exposed to an equimoiar mixture of TFA/TFAA and heated for 2h to form the quaternary stereocenter at C7 with the desired stereochemistry, but at C6 a mixture of epimers were formed. Reductive desuifurization with Raney-Ni followed by photochemical rearrangement afforded the natural product. 

A Pummerer-initiated cascade reaction has also been used as a method for generating isomiinchnones for further use in cycloaddition chemistry. For example, treatment of sulfoxide 23 with acetic anhydride first resulted in the formation of a reactive thionium ion that reacted with the distal amide carbonyl group to produce isomunchnone 24 (Scheme 6) (99JOC2038). Exposure of 24 to a dipolarophile, such as iV-phenylmaleimide, resulted in 1,3-dipolar cycloaddition to give 25 as a single diastereomer in 85% yield. 

Padwa and co-workers also used this methodology to synthesize the aza-fluorenone alkaloid onychine 570 (Scheme 4.26). The sulfoxide 565 was prepared from 2-(2-butenyl)benzoic acid in four steps. Generation of the thionium ion 566 under standard Pummerer reaction conditions was followed by cyclization to isomunchnone 567 and then to cycloadduct 568, which loses water to form a-pyridone 569. Subsequent manipulation involving deoxygenation and debenzyla-tion completed the synthesis. 

The generation of thionium ions from sulfoxides bearing an a-hydrogen can be carried out by using TMSOTf-EtsN as initiator to afford Pummerer reaction products (eq 117). ... 

Since thionium ions, e.g. 177 also can be generated by treatment of thioacetals or thioketals with dimethyl(methylthio) sulfonium tetrafluor-oborate (DMTSF), a similar cyclization sequence occurred when the amido thioketal 176 was used as an educt (Scheme 30). Starting from the educt 176 the ring formation according to route B/C(a) takes place giving 71% of 15,16-dimethoxy-8-oxoerythrinane (68) in one step (95). 

In efforts to complete the synthesis of strictamine (6) via this tactic, the Bosch group explored multiple routes to generate the C6—C7 bond. The possibility of using a thionium ion mediated cyclization was explored via two routes (Scheme... 

More modern definitions give the Pummerer name to the addition of nucleophiles to intermediate thionium ions, which are generated by different procedures and not necessarily from sulfoxides (connective pathway in Scheme 20.1). Depending on how this thionium intermediate is generated, and on whether it undergoes nucleophile addition, several types of Pummerer reactions exist. This chapter will focus on recent (in the last 6 years) developments and applications of Pummerer chemistry in the synthesis of conplex natural products and other structures that are difficult to prepare. Mechanistic studies that provide useful information to better plan a synthesis using Pummerer transformations are also covered. 

The second set of examples involves the use of thionium ions as electrophiles in inter- and intramolecular processes to obtain a-substituted sulfides (see 24 25, Scheme 20.7T which is the most common type of Pummerer reaction. Applications of this classical Pummerer rearrangement are exemplified in the synthesis of trans-solamin, the synthesis of indolizidine alkaloids, and the synthesis of the CDE ring of erinacine E. The first exanple fScheme 20.10 uses Pummerer chemistry in the generation of a thionium ion, which reacts in an intermolecular tin-mediated ene reaction the second one fScheme 20.11 uses Pummerer chemistry to introduce a nitrogen-containing heterocycle by intramolecular addition to form the coniceine core and the third example fScheme 20.12 is an intramolecular silicon-induced Pummerer reaction with oxygenated nucleophiles applied to the synthesis of a precursor of erinacine. Details of these Pummerer-based strategies are discussed below. 

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