Pummerer rearrangement examples

The unsaturated sulfinyl compound 105 can be converted into the iodooxathiane 107 either directly by AModosuccinimide or via the sulfoxide 106, providing the first example of an iodonium-promoted Pummerer rearrangement <00H(52)465>. 

Recently, new examples of asymmetric induction in the Pummerer reaction of chiral sulfoxides have been described. Oae and Numata (301) reported that the optically active a-cyanomethyl p-tolyl sulfoxide 275 undergoes a typical Pummerer rearrangement upon heating with excess of acetic anhydride at 120°C, to give the optically active a-acetoxy sulfide 276. The optical purity at the chiral a-carbon center in 276, determined by means of H- NMR spectroscopy using a chiral shift reagent, was 29.8%. 

Cycloadditions of dienes with oxyallyl offer the opportunity to prepare seven-membeted ring systems. This reaction has also proved to be of importance in Ae furan series. A few examples may illustrate the value of this methodology. A tandem Pummerer rearrangement and intramolecular [4-i3]-cycloaddition with a fiiran derivative has been reported <99TL545>. For a similar reaction see <99T13999>. 

Formaldehyde anion synthon ( CHO). The anion of 1 (n-BuLi, THF, 0°) is readily alkylated, particularly by primary halides. The products can he converted into aldehydes under very mild conditions. Oxidation with m-chloroperbenzoic acid gives an unstable sulfoxide, which undergoes an sila-Pummerer rearrangement to an acetal. Addition of water liberates the free aldehyde. Epoxides can also be used as electrophiles.2 3 Example ... 

New examples of application appear regularly. In the following one [248] phenylsulfenylation of nopinone (4) was followed by oxidation to the sulfoxide. Pummerer rearrangement of the latter led directly to the a-phenylthio substituted a-unsaturated ketone (6) (overall yield 94%), starting material for further elaboration of natural sesquiterpene synthesis via 4,4-disubstituted nopinones (7). 

Vinyl sulfoxides (221), which are aldehyde a-cation equivalents, and vinylthiolium ions (230), which are a.jj-unsaturated carbonyl 3-cation equivalents, are also suitable acceptors for silyl ketene acetals and enol silyl ethers (Scheme 36). Kita reports that the bulky r-butyldimethylsilyl ketene acetals and tri-methylsilyl ketene acetals form 1 1 adducts (224) and 1 2 adducts (225) with (221), respectively 91 mechanistically, these additions proceed via an initial Pummerer rearrangement The vinylthiolium ion additions are notable for their synthetic flexibility for example, additions to the ketene dithioacetal (229) proceed with higher diastereoselectivity than the corresponding enolate additions to a,3-unsaturated esters.9 lc,91d... 

The Pummerer rearrangement of sulfoxides with acid anhydrides has been extensively utilized as a method for the synthesis of a-substituted sulfides. When a,(3-unsaturated sulfoxides are used, the initial formed oxysulfonium ion may undergo two different pathways the additive Pummerer reaction or the vinylogous Pummerer reaction. The following sections will consider examples from both pathways. 

The first example of the sila-Pummerer rearrangement, which consists in the thermal conversion of sulfoxide 169 into O-silylated cyclic 0,S-acetal 170, has been described <1999TL185>. As shown in Scheme 29, a 1,3-migration of silicon atom to a sulfoxide oxygen resulted in ring expansion. 

In the examples of the Pummerer rearrangement presented above, the common feature has been the formation of an a-thiocarbocation, which is then captured either intermolecularly or intramolecularly by a nucleophilic species. There are of course other outlets through which the a-thiocarbocation can pro-... 

In comparison to some of the other activation methods however, the dimethyl sulfoxide-acetic anhydride procedure has certain disadvantages. The method often requires the use of long reaction times (1 24 h), which can result in many side reactions, especially with sensitive substrates. Notable in this respect is that it is not uncommon for this procedure to result in the formation of substantial yields of the thiomethyl ethers obtained from the Pummerer rearrangement product as described above. In fact upon attempted oxidation of cholesterol with this system, the major product obtained was the corresponding (methylthio)methyl ether. Acetates may also be formed if the alcohol is unhindered. For example the sugar derivative (9) reacts under these conditions to form an enol acetate (derived from the requir carbonyl compound) in 40% yield contaminated with 30% of the acetate (10 equation S). ... 

Use of trimethylsilyl triflate to bring about Pummerer rearrangement requires the presence of a base such as a tertiary amine (vide supra equations IS and 26). In some instances, involving attempts to alkylate Pummerer intermediates with silyl enol ethers under such conditions, the base has been found to compete as a nucleophile. In the absence of the silyl enol ether, amine iuldition can be very efficient. For example, treatment of methallyl phenyl sulfoxide with diisopropylethylamine and trimethylsilyl triflate in dichloromethane (equation 29) at 0 C yields the anunonium triflate indicated in 91% yield. Other tertiary amines which undergo this reaction include triethylamine and A(//-diethyltrimethylsil-amine. In the latter case with allyl phenyl sulfoxide as the substrate and a mildly acidic work-up, the Mannich derivative shown in equation (30) can be obtained in 90% yield. ... 

A few examples of additive Pummerer rearrangements are known involving direct conversion of a, -unsaturated sulfoxides into a,3-disubstituted sulfides. Scheme 4 illustrates two general pathways for such processes and specific examples of each are known. For example, alk-l-enyl phenyl sulfoxides... 

The normal protic Pummerer rearrangement has its metallic equivalent in the stannyl (and silyl) Pummerer reaction,46 9 for example 47... 

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