Selenium electrophiles, chiral

The mechanism of the asymmetric methoxyselenenylation of alkenes has been investigated using competition experiments and computational methods (Scheme 8). The experiments have demonstrated that the formation of the intermediate seleniranium ion (48) is reversible. Ions of type (49), generated in the addition of chiral selenium electrophiles to alkenes, are the key intermediates in the asymmetric methoxyselenenylation their stability is strongly dependent on the strength of the selenium-heteroatom interaction. Calculations have been carried out to determine the relative stabilities of the diastereoisomeric seleniranium ions (49). The results obtained from the calculations support the experimental flndings. ... 

Chiral solvomercuration was accomplished by carrying out the reaction of alkenes with Hg(OAc)2 in the presence of chiral quaternary ammonium salts synthesized from natural ephedrine.642 Chiral secondary alcohols may be isolated with ee values up to 96%. Chiral nitrogen-containing diselenides are transformed by perox-odisulfate to selenium electrophiles, which may add to alkenes to form oxyseleny-lation products. These are, however, not isolated but oxidized to induce oxidative p-hydride elimination to afford chiral allyl methyl ethers with ee values up to 75%.643... 

Recently, Wirth and Uehlin further extended the selenium-based solid-phase assisted chemistry by introducing a new polymer-bound chiral selenium electrophile 29. Regio-and stereoselective 1,2-methoxyselenylation of propenylbenzene gave intermediate adduct 30 which was cleaved by oxidative elimination via the selenoxide to yield the corresponding allylmethyl ether (Scheme 12) [38]. 

Well before the wide use of organoselenium compounds in chemistry, it was discovered that electrophilic selenium compounds of the type RSeX add stereospecifically to alkenes.45 Since that time this reaction has been an important tool in the portfolio of organic chemists and has been used even for the construction of complex molecules. Comprehensive reviews on this chemistry have appeared46-49 and in recent times the synthesis of chiral selenium electrophiles and their application in asymmetric synthesis has emerged. As shown in Scheme 1, the addition reactions of selenium electrophiles to alkenes are stereospecific anti additions. They involve the initial formation of seleniranium ion intermediates 1 which are immediately opened in the presence of nucleophiles. External nucleophiles lead to the formation of addition products 2. The addition to unsymmetrically substituted alkenes follows the thermodynamically favored Markovnikov orientation. The seleniranium ion intermediates of alkenes with internal nucleophiles such as 3 will be attacked intramolecularly to yield cyclic products 4 and 5 via either an endo or an exo pathway. Depending on the reaction conditions, the formation of the seleniranium ions can be reversible. 

Figure 3 Selected chiral diselenides as precursors for the corresponding selenium electrophiles.

Many of the chiral selenium electrophiles have also been employed in cyclization reactions. Various internal nucleophiles can be used and access to different heterocycles is possible. Not only oxygen nucleophiles can be used for the synthesis of heterocyclic compounds, but also nitrogen nucleophiles are widely employed and even carbon nucleophiles can be used for the synthesis of carbacycles with new stereogenic centers. Oxygen nucleophiles have been widely used and some selected examples of selenolactonizations of unsaturated acids 50 and 52 and seleno-etherifications of unsaturated alcohols 54 and 56 are shown in Scheme 10. 

These reactions have also been performed using enantiomerically pure selenium electrophiles to access heterocyclic compounds with stereogenic centers. The yields and selectivities obtained using some selected chiral electrophiles generated from the diselenides are given in Table 2. 

If the optically active organoselenium compounds can be used for Tomoda s or Tiecco s catalytic system using diselenide and persulfate (see Sect. 4.1), a catalytic asymmetric oxidation reaction should be possible. The enantioselectivity of the produced allylic compounds may depend on the stereoselectivity of the oxyselenenylation step of chiral selenium electrophiles with prochiral alkenes. Several groups have reported diastereoselective oxyselenenylation using a variety of chiral diselenides in moderate to high diastereoselectivity [5 f, g, i, 25]. The detailed results are reviewed in Chap. 2. 

Recently, the semi-synthesis of Vancomycin (48) on solid supports was accomplished using an allylic linker (Scheme 3.2) [123, 124]. Polymer-bound chiral electrophilic selenium reagents have been developed and applied to stereoselective se-lenylation reactions of various alkenes (Tab. 3.9) [125]. 

With other electrophiles, ferrocenes 12 and 13 could be obtained, bearing a selenium group [19] or a silanol moiety [20], respectively, in the ortho position. Those compounds proved to be catalytically active as well, and in particular 13 was of interest, since - to the best of our knowledge - it was the first silanol ever used as a chiral ligand in asymmetric catalysis. Details of this study will be discussed below. 

The popular approach to tetrahydrofurans involves an electrophilic process and the commonly used electrophiles for the cyclization are acids, oxygen, halogen, mercury (see Section 3.11.2.2.9) and selenium. The ionic hydrogenation of furans with excess triethyl-silane in trifluoroacetic acid affords high yields, e.g. 2-methylfuran is reduced to 2-methyl-tetrahydrofuran and 2-ethylfuran to 2-ethyltetrahydrofuran (see Section 3.11.2.5). The synthesis of several dihydro and tetrahydrofurans containing natural products by chirality transfer from carbohydrates has been used successfully for total synthesis, e.g. (-)-nonactic acid. A reasonable yield of 2-alkyltetrahydrofuran was prepared from 4-alkylbut-l-en-4-ol by hydroboration followed by cyclization with p-toluenesulfonic acid. 

A number of useful enantioselective syntheses can be performed by attaching a chiral auxihary group to the selenium atom of an appropriate reagent. Examples of such chiral auxiliaries include (49-53). Most of the asymmetric selenium reactions reported to date have involved inter- or intramolecular electrophilic additions to alkenes (i.e. enantioselective variations of processes such as shown in equations (23) and (15), respectively) but others include the desymmefrization of epoxides by ringopening with chiral selenolates, asymmetric selenoxide eliminations to afford chiral allenes or cyclohexenes, and the enantioselective formation of allylic alcohols by [2,3]sigmafropic rearrangement of allylic selenoxides or related species. 

There have been many studies on the use of chiral electrophilic selenium reagents for stereoselective additions to alkenes <1998JA3376, B-1999MI35, 1999T1, 2000AGE3740> with notable diastereoselectivity in some cases. 

Synthesis of furans with chiral substituents with high diastereoselectivity was achieved by using an optically active electrophilic selenium reagent via a carboselenenylation reaction of simple aryl-conjugated alkenes <05AG(E)3588>. 

Triazole ring opening of these chiral alcohols with the formation of chiral 2,6-disubstituted pyridines are known. The reactions are performed with acetic acid, 2.5 M sulphuric acid, and selenium dioxide as electrophiles (07T10479). 

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