Selenoxide-based elimination

Selenoxide syn-eliminations are another reaction type favoured by less polar solvents (Reich, 1979). The planar 5-membered, pericyclic transition state for syn-elimination of [39] was mimicked by the racemic proline-based cis-hapten [39] to give 28 monoclonal antibodies (Appendix entry 8.5) (Zhou et al., 1997). Abzyme SZ-cts-42F7 converted substrate [40] exclusively into... 

Selenides eliminate readily without a base. They are generally prepared from enolate anions by reaction with diphenyldiselenide or phenylselenyl bromide to give phenylselenides. The phenylselenides are oxidized with sodium periodate, hydrogen peroxide, or peracids to the selenoxides, which eliminate even at room temperature to afford the a,p-unsamrated ketones and esters [107]. 

Sulfonesand sulfonic esters can also be alkylated in the a position if strong enough bases are used. Alkylation at the a position of selenoxides allows the formation of alkenes, since selenoxides easily undergo elimination (17-11). 

Selenoxides are even more reactive than sulfoxides toward (3-elimination. In fact, many selenoxides react spontaneously when generated at room temperature. Synthetic procedures based on selenoxide eliminations usually involve synthesis of the corresponding selenide followed by oxidation and in situ elimination. We have already discussed examples of these procedures in Section 4.3.2, where the conversion of ketones and esters to their a, (3-unsaturated derivatives is considered. Selenides can... 

Glycals are also available from 2-deoxy sugars by acid- or base-induced eliminations ofanomeric substituents. These methods are limited by the availability ofthe 2-deoxy sugars, for which the glycals themselves are the most obvious synthetic precursors. However, examples of these methods (Scheme 5.43) are in the direct preparation oftri-O-benzyl-D-glucal (14) from 2-deoxy-tri-O-benzyl-D-glucopyranose (13) via its 1-O-mesylate [117], and di-O-benzyl-D-ribal (16) from the phenylselenide 15 via oxidation to the selenoxide followed by elimination [118]. 

Resin-bound selenium has been used as a linker for alkenes in two ways (a) as an oxidant-sensitive linker (selenoxides readily undergo [5-elimination at room temperature Entries 6-8, Table 3.43 [767-773]), or (b) as a linker cleavable by tin radicals (Figure 3.37 Entries 9 and 10, Table 3.43). The main advantages of selenides as linkers are their stability under a broad variety of (non-oxidizing) reaction conditions, including high temperatures and treatment with acids or bases, and the mild conditions required for their cleavage. 

P-Sultams.1 Reaction of 1 with imines and a base (usually pyridine) in THF results in 4-carbomethoxy-l,2-thiazetidine 1,1-dioxides (2) in 20-93% yield. All products have the trans-orientation. The N-unsubstituted P-sultams can be obtained by use of phenylselenenylethyl as the R group. This R group can be replaced by hydrogen in 70-90% yield by selenoxide elimination to an enamide, which is then treated with I2 and Na2S03.2... 

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]. 

The asymmetric elimination has so far generally been carried out by enan-tioselective deprotonation using chiral bases [15]. Therefore, if an elimination from optically active selenoxides gave optically active alkenes, the reaction may provide a new methodology for asymmetric elimination to form a carbon-carbon double bond under mild conditions. A few examples of asymmetric selenoxide elimination are described below. 

The first synthesis of d4T was accomplished in 1966 by Horwitz from l-(2-deoxy-3,5-epoxy-/3-D-r/2reo-pentosyl)thymine abstraction of a proton from the 2 -position by potassium butoxide in DMSO resulted in an opening of the oxetane ring and formation of d4T. Other syntheses were based on the elimination of sulfoxide or the selenoxide moiety placed at the C-2 position in the nucleoside, which was prepared from cheap lactone 6 (O Scheme 7) [6]. 

Masamune has also completed a synthesis of tylonide hemiacetal (291) based on the creative use of enantioselective aldol condensations, as shown in Scheme 2.26. The aldol condensation of 328, derived from (/f)-hexahydromandelic acid and prop anal, was found to be >100 1 diastereoselective, affording the 2,3 syn compound 329 in 97% yield. Transformation to the p,7-unsaturated ester 330 occurred via selenoxide elimination and periodate cleavage followed by esterification. Formation of the silyl ether, reduction, and protection of the ester followed by ozonolysis of the terminal olefin gave the diol-protected aldehyde 331. The C-11 to C-15 segment 332 was then completed via chain elongation and a subsequent reduction-oxidation sequence in 34% overall yield from 330. 

Oxidation to the selenoxide 39 and thermal elimination (chapter 32) produces a new alkene 40 that forms an epoxide 41 on the outside face again. At this point every carbon atom in the six-membered ring is functionalised, five oxygen-based and one nitrogen, and this all started with symmetrical cyclohexadiene. Each functional group was selectively introduced from an alkene. 

Allyl vinyl ethers have also been obtained by elimination reactions, e.g., intramolecular bromo-etherification/base-catalyzed hydrogen bromide elimination164 166( 0r the phenylseleno etherifi-cation/selenoxide elimination reaction158 167. Tertiary allylic alcohols have been vinylated by a Michael-type addition to a vinyl sulfoxide followed by elimination of benzenesulfenic acid168. 

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