Chiral sulfoxides, Pummerer rearrangement

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

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%. 

The Pummerer rearrangement has also been used to transform the 4-tolylsulfinyl group, which is an effective chiral auxiliary, into other functionalities via the aldehyde. Thus, chiral /> -(ben-7yloxy)-/J-(fluoroalkyl) sulfoxides 11 have been transformed into aldehydes 12 in a two-step process.7,8 The 3,3-difluoro-substituted aldehydes 12 can be converted directly into a variety of other functional groups without isolation. The chiral center at C2 is derived from the corresponding chiral / -oxo sulfoxide, which can be reduced diastereoselectively due to the presence of the chiral 4-tolylsulfinyl group.7,8 Diastereoselective reduction of fluorine-free fi-oxo sulfoxides has been intensively studied, especially in the laboratories of Solladie.9... 

Similarly, enantiopure 3-substitutcd-/V-rnc thy I benzyl /3-sultams have been converted into A -methylbenzyl-a-amino acid thioesters via sulfenylation and Pummerer rearrangement with high or complete retention of configuration. Chiral sulfoxides were prepared by sulfenylation followed by oxidation of trans-isomers as two separable A and B stereoisomers. Treatment with TFAA gave chiral cr-amino acid thioesters in high yields with a de > 90%. Slight epimerization of the cr-chiral center of the cr-phenyl thioesters has been observed under the reaction conditions whereas no epimerization was observed in the case of -/-butyl thioesters (Scheme 28) <1998JOC8355>. 

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. 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

Mikolajczyk, M., Zatorski, A., Grzejszczak, S., Costisella, B., and Midura, W., a-Phosphoryl sulfoxides. Part 4. Pummerer rearrangements of a-phosphoryl sulfoxides and asymmetric induction in the tt ansfer of chirality from sulfur to carbon, J. Org. Chem., 43, 2518, 1978. 

We view acetylenic sulfoxide 1 as a two-carbon synthon in alkaloid synthesis. Our general approach, as depicted in Scheme 4, called for a Michael addition of Nu1 to the terminal acetylenic position followed by a cyclization by Nu2 (an intramolecular second Michael addition). This Michael addition cyclization step will build up the basic skeleton of the alkaloid system and at the same time control the absolute stereochemistry of the newly created chiral center through asymmetric induction of the chiral sulfoxide moiety. Finally, the sulfoxide can be transformed to another functional group (X) or used to promote the formation of another bond with Nu3 via trapping of the sulfenium ion intermediate under Pummerer rearrangement conditions (Scheme 4). 

In most cases, the sulfoxides produced after the asymmetric transformation are reduced with sodium or aluminium amalgam, or Raney nickel. The sulfoxide may also be reduced by LiAffl into a sulfide, winch after quaternarization becomes a leaving group [474], If the carbon skeleton of the substrate bears appropriate substituents, the sulfoxide can suffer [2,3] sigmatropic rearrangements [497, 498] or Pummerer rearrangements. In all these types of applications, the chiral auxiliary is never recovered. 

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. 

Pummerer rearrangement. Sulfoxides are converted into a-siloxy sulfides, in which the new 0-C bond is anti to the original S-0 bond. Accordingly, the rearrangement of chiral sulfoxides is enantioselective. The method is applicable to synthesis of /3-lactam precursors. ... 

A second, isolated example of construction of useful chiral azetidinones by the N-C4 bonding strategy utilizes the phenylsulfinylpropionamide 93a as starting material. Treatment of this compound with TMSOTf/TEA promoted a Pummerer rearrangement concerted with lactamization to 93b [43a]. Starting from the ( — )-sulfoxide enantiomer, obtained by HPLC resolution with a chiral stationary fase (cellulose tribenzoate), the 4/ -phenylthio enantiomer was obtained in 67% optical yield [43b]. Hydroxyethylation of this intermediate is described in Sect. 3.1. 

The one-electron oxidation of iV-benzylphenothiazine by nitric acid occurs in the presence of /i-cyclodextrin, which stabilizes the radical cation by incorporation into its cavity. The reaction is inhibited by adamantane, which preferentially occupies the cavity. Novel Pummerer-type rearrangements of / -sulfinylphenyl derivatives, yielding /7-quinones and protected dihydroquinones, and highly enantioselective Pummerer-type rearrangements of chiral, non-racemic sulfoxides have been reviewed. A comprehensive study has demonstrated that the redox potential for 7- and 8-substituted flavins is linearly correlated with Hammett a values. DFT calculations in [3.3.n]pro-pellanes highlight low ionization potentials that favour SET oxidative cleavage of the strained central C-C bond rather than direct C-H or C-C bond attack. Oxidations and reductions in water have been reviewed. ... 

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