Pummerer reaction, asymmetric

In 1974 the first example of asymmetric induction in an intramolecular Pummerer reaction was observed and reported. Stridsberg and AUenmark (300) treated optically pure o-benzylsulfinylbenzoic acid 271 with acetic anhydride in the presence of dicyclohexyl-carbodiimide (DCC) and found that the Pummerer reaction product, 3,l-benzoxathian-4-one 272, was optically active. The sign and optical rotation values ([alp varied from +42° to -11°) of 272... 

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%. 

A similar extent of asymmetric induction was observed (88) in the Pummerer reaction of optically active a-phosphoryl sulfoxide 49, which results in the formation of the corresponding optically active a-acetoxy a-phosphorylmethyl sulfide 277. 

DCC) proceeds with much higher enantioselectivity (e.e. up to 45%). Likewise, a much higher degree of asymmetric induction was observed in the Pummerer reaction of optically active a-carbonyl-substituted sulfoxides carried out in the presence of DCC (303) to give the a-acetoxy-a-p-toluenesulfenylacetic acid derivatives 278. 

As previously described, the effect of substituent groups on the silyi function is an important factor in terms of determining the reaction course. Table 4 shows the ratio of the products in the Pummerer reaction using various SKAs.33 These results suggest that carbon-carbon bond formation preferentially occurs when using a small silyi function such as the trimethylsilyl function. This tendency was observed in another substrate which has asymmetric carbon at the (3-position of the sulfur atom (Table 5).33 Interestingly, the syn-selectivity of the rearrangement product... 

Asymmetric Pummerer rearrangement is a very attractive reaction as previously described. In particular, the reactions induced by SKA work well, and may be synthetically exploited in many cases. The results described here demonstrate that the stereoselective a-deprotonation of the sulfoxide is a prerequisite process for asymmetric induction in the Pummerer reaction. Since many kinds of synthetic and enzymatic preparative methods of optically pure sulfoxides have been developed, the present Pummerer-type reaction will be applicable to many other chiral sulfoxides with one a-substituent, chiral vinylsulfoxides and chiral co-carbamoylsulfox-ides, thus leading to enantioselective syntheses of many new bioactive compounds in the near future. 

In many respects the Pummeter reaction can be regarded as the sulfur version of the Polonovski reaction (and vice versa), and by analogy to the Polonovski reaction the central intermediate is a sulfur-stabilized carbocation (thionium ion). Although the existence of this species is only transient, it reacts to give a number of different products, e.g. a-acetoxy sulfides, vinyl sulfides, cationic cyclization products, etc., depending upon the sulfoxide structure and reaction conditions. Other reaction pathways ate specific to the Pummerer reaction as a result of sulfur s ability to expand its valence shell (additive Pum-merer reactions). A moderate degree of asymmetric induction is also observed in certain Pummerer reactions, where optically pure sulfoxides are substrates. 

In this class of Pummerer reactions subsequent formation of the a-acyloxy sulflde involves, in the majority of instances, an intermolecular acyloxy migration. The reaction of p-tolyl benzyl sulfoxide with acetic anhydride is an exception. However, even in this case no asymmetric induction is observed. ... 

Compound (116) is obtained in 41% chemical yield and 67% ee, one of the highest reported cases of asymmetric induction in the Pummerer reaction. The use of a silicon activating reagent in this reaction is crucial as the reaction of sulfoxide (115 R = Me) with trifluoroacetic anhydride gave compound (119), presumably via intermediates (117) and (118). This latter result points to the possibility that this and... 

Numata, T., Ito, O., Oae, S. Unusually high asymmetric induction in the Pummerer reaction of optically active sulfoxides. Tetrahedron Lett. 1979, 1869-1870. 

Ruano, J. L. G., Paredes, C. G. Intramolecular asymmetric Pummerer reactions as a key step in the synthesis of bicyclic precursors of anthracyclinones. Tetrahedron Lett. 1999,41,261-265. 

R = Me) hydrolysis of the intermediate affords the 4-hydroxy compound (127 R = OH) in low yield (Equation (14)) <85CJC33I3>. Reaction of the chiral oxathiolanone oxide (128) with TFAA and an arene gives some asymmetric induction in the formation of (129) (Equation (15)) <90TA143>. With the unsubstituted compound (39), Pummerer reaction allows the introduction of a variety of nucleophiles at the 4-position to give (130) and oxidation of the intermediate with pyridine N-oxide affords access to the little known 4,5-dione (35) (Equation (16)) <93JHC663>. 

The Pummerer reaction, whose key step is a [2,3]-sigmatropic rearrangement, has never been observed to lead to efficient transfer of chirality starting from chiral sulfoxides in the presence of acetic anhydride [1632, 1633], A modification via silyloxysulfides, generated with O-methyl-OTBDMS ketene acetal at 65°C, allows asymmetric silicon-induced Pummerer reaction from chiral sulfoxides 10.29 with a high chirality transfer [1634] (Figure 10.11). The ( S)-sulfoxides generate the (5)-secondary ethers and vice-versa. 

New modifications of the traditional approach to isoquinoline synthesis via carbocation intermediates continue to be reported. Abnormal products of the Bischler-Napieralski reaction were observed <97JCS(P1)2217>. A stereoselective introduction of a quaternary carbon center in the A-acyliminium cyclization (Scheme 14) of the chiral enamide 46 affords an asymmetric synthesis of tetrahydroisoquinolines <97T2449,3045>. An asymmetric Pictet-Spengler reaction has been developed mediated by the chiral urethane 47 <97T16327>. A Pummerer reaction of A-acyl-A-(aryl)methyl-2-(phenylsulfinyl)ethylamine allows cyclization to the 4-phenylthio-... 

Asymmetric Pummerer reactions with chiral sulfinates have been moderately successful but avoid pathway A, or more specifically, an achiral thionium ion, although... 

As was evident in the previous section, the main substrates for classical Pummerer reactions are sulfoxides. These are commonly obtained by the oxidation of sulfides. The oxidation can be performed with traditional oxidizing agents, such as Nal04, m-CPBA, and H2O2. Furthermore, the use of catalytic asymmetric methods for the selective oxidation of sulfides is well documented, and several synthetically applicable methods are described in the literature. ... 

A very interesting approach to optically active sulphoxides, based on a kinetic resolution in a Pummerer-type reaction with optically active a-phenylbutyric acid chloride 269 in the presence of /V,A -dimethyIaniline, was reported by Juge and Kagan332 (equation 149). In contrast to the asymmetric reductions discussed above, this procedure afforded the recovered sulphoxides in optical yields up to 70%. Chiral a, /1-unsaturated sulphoxides 270 were prepared via a kinetic resolution elaborated by Marchese and coworkers333. They found that elimination of HX from racemic /i-halogenosulphoxides 271 in the presence of chiral tertiary amines takes place in an asymmetric way leading to both sulphoxides 270 and 271, which are optically active (optical yields up to 20%) with opposite configurations at sulphur (equation 150). 

The use of chiral sulfoxides to transfer the chirality from sulfur to the a carbon has been investigated, and the high asymmetric induction observed in chiral acyclic sulfoxides using a silicon-induced Pummerer-typc reaction is noteworthy [249]. 

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