Enolates samarium

The occurrence of the indole subunit is well established within the class of natural products and pharmaceutically active compounds. Recently, the Reissig group developed an impressive procedure for the assembly of highly functionalized in-dolizidine derivatives, highlighting again the versatility of domino reactions [8]. The approach is based on a samarium(II) iodide-mediated radical cydization terminated by a subsequent alkylation which can be carried out in an intermolecular - as well as in an intramolecular - fashion. Reaction of ketone 3-11 with samarium(ll) iodide induced a 6-exo-trig cydization, furnishing a samarium enolate intermediate... 

Benzenetricarbonyl trichloride and l,2,4,5-tetrakis(bromomethyl) benzene were employed as multifunctional initiators for the synthesis of 3-and 4-arm PTHF stars, respectively [147]. The living ends were reacted with sodium 2-bromoisobutyrate followed by reduction with Sml2. The samarium enolates, thus formed were efficient initiators for the polymerization of MMA to give the (PTHF-fo-PMMA) , n = 3 or 4 star-block copolymers, according to Scheme 71. 

The acetate function of 98 was then cleaved by treatment with samarium diiodide in methanol in high yield (81 %) [44], A potential mechanism for this transformation is shown in Scheme 3.18. Reduction of the ketone function forms a samarium ketyl radical (103). Transfer of a second electron forms a carbanion (104) which undergoes p-elimination of acetate to generate the samarium enolate 105. Protonation and tautomerization then affords the observed product 107. 

Samarium enolates 60 can be easily prepared by reduction of ct-bromocarboxylic acid esters with SmT. These enolates mediated well-defined synthesis of star-shaped block co-polymers 61 (Scheme 21 ).32 32l Sml3 also mediated the formation of samarium enolates. Phenacyl thiocyanate 6233 and cr-haloketone 6434 are converted to samarium(lll) enolate intermediates 63 and 65, respectively, which undergo addition to benzaldehyde derivatives affording the corresponding oy i-unsaturatcd ketones as shown in Schemes 22 and 23. 

An unusually strong CD for open-chain ketones 141 was recently reported327. Ketones 141 were formed by hydrogenation of /J,y-unsaturated precursors (As not reported) which were obtained by enantioselective protonation of samarium enolates (Table 8). 

Takeuchi and coworkers have achieved the catalytic enantioselective protonation of a samarium enolate 45 in the THF/FC-72 [F3C(CF2)4CF3] biphasic system using a C2-symmetric chiral diol 5 (DHPEX) or a fluorinated chiral alcohol 6 as a catalyst and a fluorinated achiral alcohol 46 (Scheme 3) [11]. The fluorinated biphasic system was more effective than THF alone, and enantioselectivities near maximum values were obtained in the reaction. In addition, it was unnecessary to add the achiral alcohol 46 slowly to the reaction mixture. 

Tetradentate chiral proton donors have been used for the asymmetric protonation of samarium enolates formed by the Sml2 reduction of a-heteroatom-substituted carbonyl compounds. For example, Takeuchi examined the reduction of a-heterosubstituted cyclohexanone 12 using Sml2 and the BINOL-derived chiral proton source 13.41 Ketone 14 was obtained in good yield and high enantiomeric excess (Scheme 2.11). Coordination of the proton source to samarium is key to the success of the transformation.41... 

Analogous asymmetric, samarium Reformatsky reactions of chiral 3-bro-moacetyl-2-oxazolidinones have been described by Fukuzawa.140 For example, reduction of 124 with Sml2 generates a samarium enolate that then reacts with pivalaldehyde to give the a-unbranched (I-hydroxycarboximide 125 in 87% yield and in high diastereoisomeric excess (Scheme 5.89). The reaction is synthetically noteworthy as highly diastereoselective acetate aldol processes are difficult to achieve. Sm(III) ions are likely to play an important role in the... 

C but isomerise to the more stable enolate on warming (Scheme 5.91). The use of two different ot-halo esters allows access to more complex samarium enolates before quenching with benzaldehyde.144... 

In the absence of 2,2,2-trifluoroethanol, low yields of cyclobutanols were obtained. It is thought that the acidic proton donor prevents elimination of the silyloxy group by rapid quenching of the samarium enolate 37 formed in the cyclisation (Figure 7.1).57... 

It was rationalized that the KDO C-glycoside is generated only in the a-configuration because the a-face of the samarium enolate intermediate 38 is much less sterically hindered than P-face (Scheme 9b). 

Intermediate samarium enolates derived from ketones 1522 or 1525 could stereoselectively be trapped with allyl halides, leading to tricycles 1524 and 1526. The intramolecular alkylation by the chloroalkyl terminus of compound 1527 led to tetracyclic compound 1528 with satisfactory efficiency. These cascade reactions selectively generate three continuous stereogenic centers, including a quaternary carbon atom at the 3-position of the dihydroindole moiety, a structural motif of many indole alkaloids. 

When a-halo ketones are treated with diiodomethane and samarium at 0 °C, cyclopropanols can be obtained in reasonable yields. Curiously, under the same conditions 1,2-dibenzoylethane also leads to cyclopropanol products (equations 34 and 35). Several pathways for conversion of a-halo ketones to the observed cyclopropanols can be envisioned. It has been proposed that the mechanism of this reaction involves reduction of the a-halo ketone by Sm (or Smh) to a samarium enolate. Cyclopropanation of this enolate with a samarium-based carbenoid subsequently provides the observed product. 

Under appropriate conditions, the samarium enolates can effectively be quenched by electrophiles on either the oxygen or carbon atom. ... 

The samarium enolate radicals were also trapped intermolecularly, with formation of new carbon-carbon bonds, by quenching the reactions with suitable electrophiles The occurrence of these tandem rearrangements was possible because the samarium(II) iodide acted as a clean one-electron reductant and also generated the metal enolates. 

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