Ring synthesis Pummerer rearrangement

Methods for the construction of the thieno[2,3-c]pyridine skeleton based on the formally simultaneous formation of both the pyridine and thiophene rings were documented. Under the Pummerer rearrangement conditions, ( -s ul liny lain idc 222 underwent a cascade transformation into 223, which was oxidized to fused lactam 224 in low yield (1999JOC2038). Data on the use of cascade transformations, including the Pummerer rearrangement - cycloaddition sequence, in the synthesis of complex heterocyclic systems were summarized in a review (1997S1353). 

Indole synthesis. This Michael acceptor reacts with o-lithio-N-Boc-aniline. The product undergoes a sila-Pummerer rearrangement to induce ring closure. Indoles are obtained on elimination of the [PhSH] element. 

Lactaldehyde 689 has been used as the chiral source in an interesting synthesis of unnatural D-threonine (695) [204] (Scheme 93). The first of the two most important reactions in the sequence is the conversion of 691 to 692. The transformation proceeds by partial methano-lysis of the trichloroacetyl group followed by intramolecular conjugate addition, which forms the oxazolidinone ring in 692 stereospecifically at C-4 and C-5. The second critical reaction is a Pummerer rearrangement of 693 to 694, which introduces the requisite carboxyl function (as... 

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. 

Pummerer rearrangement processes have been described in several papers. -Typically, RS(0)(CHg)4SR-> RSCH=CH(CHa)2SR on treatment with AcjO, and the formation of the ring-expanded lactone via 2-hydroxy-2-methylsulphinylmethyltetrahydrofuran, illustrate the possibilities of these processes in synthesis. A silicon-Pummerer rearrangement, MeaSi-CH,jS(0)Ph-> CH8=S(OSiMea)Ph McsSiOCHaSPh, effected at 60 °C, has been studied further some seven years after the process was discovered substantial amounts of vinyl sulphides are also formed. 

Scheme 2.146. Synthesis of several natural products via Pummerer-type rearrangement/ 1,3-dipolar cycloaddition/ring-opening reactions.

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