Selenation—elimination

Compound 68 was subjected to another annelation with MVK to give the tricyclic s/nro-ketone 21. It was also transformed to. sp/ro-dienone 72 via a selenation-elimination process. 

The roaster product is then charged to the Dorn furnace where it is melted and the resulting metal is fire-refined to eliminate the arsenates, selenates, antimonates, teUurates, and residual copper. 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

The oxidation is regarded as taking place by an electrophilic attack of selenium dioxide (or selenous acid, H2Se03, the hydrate) on the enol of the ketone or aldehyde. This is followed by hydrolytic elimination of the selenium.258... 

The diol function of 130 was protected as its acetonide 131 (88 %). Next, the enone function was installed by a-selenation of the enoxysilane, followed by peroxide oxidation and elimination (57 % over two steps). Finally, the unsaturated ketone 132 was homologated by 1,4-addition of trimethylsilylmethyl magnesium chloride, trapping with chlorotrimethylsilane, and reoxidation, to afford the target 117 (88 %). 

Formate esters behave as typical carbonyl compounds in reactions with a number of ylides, eliminating phosphine oxide and forming vinyl ethers, e.g. (33).35 Stabilized phosphoranes are able to condense with the carbonyl group of cyclic thioanhydrides (34).38 Quinoline derivatives, e.g. (35), are obtained from the condensation of dicar-boalkoxy-ylides with isocyanates.37 Benzoyl isothiocyanates and keto-phosphoranes give quantitative yields of (36), which are unreactive in Wittig reactions but can be readily oxidized by selenous acid.38 The products obtained from reactions (Scheme 9) with the triazolinedione (37) depend upon the stability of the ylide used.39... 

The far more expedient pathway involves gaining direct access to 795 by cuprate addition-selenation and subsequent elimination (Scheme XCV). In this way, modhephene can be produced in only six steps. 

The synthetic applicability of the electrochemical oxy-transposition may be demonstrated by the one-step synthesis of d -dihydroactinidiolide 60 from the carboxylic acid 59 in 73 % yield. The lactone 60 may be produced by electrochemical intramolecular oxyselenylation followed by elimination of selenic acid (Scheme 3-21)68>. 

Fig. 25. RDFs for 1 M erbium(III) perchlorate and selenate solutions after elimination of nonmetal interactions. The monodentate bonding of SeO is shown by the Er-Se peak in the RDF for the selenate solution.

The thermal decomposition (pyrolysis) of alkylaryl selenoxides (selenoxide pyrolysis) to an alkene and an aryl selenic acid Ar—Se—OH often takes place even at room temperature (Figure 4.10). This reaction is one of the mildest methods for introducing a C=C double bond by means of a /3-elimination. The mechanism is described by the simultaneous shift of three electron pairs in a five-membered cyclic transition state. One of these electron pairs becomes a nonbonding electron pair on the selenium atom in the selenic acid product. The Se atom is consequently reduced in the course of the pyrolysis. 

H. J. Reich, S. Wollowitz, Preparation of a,/3-Unsaturated Carbonyl Compounds and Nitriles by Selen-oxide Elimination, Org. React. 1993, 44, 1-296. 

Selenium forms weaker a-bonds than sulfur and many reactions which involve the cleavage of such bonds are faster than for analogous sulfur compounds and proceed under milder reaction conditions. The sj -elimination of selen-oxides was discovered in 1970 [9] and had a major impact on organoselenium chemistry. This reaction is about three orders of magnitude more rapid than the elimination of the corresponding less polar and less basic sulfoxides. Sigmatropic rearrangements proceed at markedly lower temperatures. These reactions are discussed in detail in Chap. 8 by Y. Nishibayashi and S. Uemura. 

Selective reduction of the C(2)=C(3) bond in naphthyridone 379 followed by treatment with BuLi in THF and methylation affords compound 380. Subsequent regeneration of the double bond occurs as a result of successive selenation, oxidation and yyn-elimination to form naphthyridone 381 (1991JHC541). Earlier, an analogous scheme has been used for the synthesis of ethyl 7-chloro-l-ethyl-6-fluoro-2-mrthyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (1989JHC1675). 

Aiylsulfinimines 8.8 are oxidized by oxaziridine 2.83 with an excellent selectivity [510] (Figure 8.5). The products of these oxidations are precursors of chiral amines and P-aminoesters ( 6.1.4 and 6.8.3). The asymmetric oxidations of aryl-selenides 8.9 with 2.83 (X = Cl) in CCI4 are also highly selective, but the rapid racemization of the selenoxides in the presence of moisture makes it difficult to isolate optically pure products [749, 1515], Uemura and coworkers [1516] have circumvented this problem by performing in situ elimination of selenic acid from the chiral selenoxide. They obtained chiral cyclohexylidene methylketones through this oxidation/elimination strategy. 

Sulfur has an antagonistic effect on several essential trace elements. Excessive amounts of sulfur can induce a secondary deficiency of copper (mainly in animals), cobalt and selenium. Ho vever, not only the sulfur amino acid cysteine but also sulfate eliminates the adverse effects of copper-, cobalt-or selenium-based toxicities (Baker and Czarnecki-Maulden 1987). Sulfate increases the urinary loss of selenate, but not of selenite this explains the assumption that there is a direct antagonism between sulfate and selenate (Schrauzer 1998). 

A more general route for this type of chiral bicyclic lactam is based on a metalation from a Meyers lactam (198) followed by alkylation, acylation, or sulfenylation to give the a-substituted bicyclic unsaturated lactams. These compounds were converted to a, -unsaturated derivatives (199) by a metalation-selenation-oxidative elimination sequence that proceeded in good overall yields (Scheme 35) <90T495l>. 

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