Acetylenic sulfones

Conjugate addition of chiral amines to allenic and acetylenic sulfones has been reported73. The reaction 112 with (—)-ephedrine gives only one of the two possible diastereomeric oxazolines in high yield (equation 89). 

The stereochemistry of the addition of amines to acetylenic sulfones has been investigated by Truce and coworkers74. Reaction of phenyl 1-propynyl sulfone with ethylamine gives a mixture of ( )- and (Z)-isomeric adducts (equation 90)75. 

Three possible mechanisms may be envisioned for this reaction. The first two i.e. 1) Michael addition of R M to the acetylenic sulfone followed by a-elimination of LiOjSPh to yield a vinyl carbene which undergoes a 1,2 aryl shift and 2) carbometallation of the acetylenic sulfone by R M followed by a straightforward -elimination, where discarded by the authors. The third mechanism in which the organometallic reagent acts as an electron donor and the central intermediates is the radical anion ... 

Keywords acetylenic sulfoxide, vinyl sulfoxide, acetylenic sulfinate, acetylenic sulfonate, 1-propene-1,3-sultone... 

Alternatively, the enamine portion may be located in the Aralkyl chain. For instance, piperidines bearing a 7-chloro substituent yielded quinolizidines 263 through a conjugate addition of the nitrogen atom to acetylenic sulfones followed by an intramolecular alkylation (Scheme 55) <2000JOC4543>. Other cyclizations that are summarized below used as starting materials piperidine derivatives obtained by similar conjugate additions to vinyl sulfones (see Section 12.01.9.3.6). 

The preparation of polystyrene-supported selenosulfonates and their application for the synthesis of acetylenic sulfones have been reported by Huang et al. (Scheme 3.3) [126],... 

The synthesis of 3- and 7-substituted indoles (184 and 185) by [3,3]-sigmatropic rearrangement of A-hydroxyindole derivatives (181) was reported (equation 54). A-hydroxyindole 181 in the presence of cyanogen bromide (182, R = Br, = N) and base afforded 183 that rearranged to the NCO substituted at position 3 and position 7, leading to two isomeric isocyanates, 184 and 185, respectively. Different behaviour was found when an acetylenic sulfone 182, R =11, R = CTos, was used where the 3-substituted indole 186 was the only rearrangement product identified. 

Mahyisulfonyl chloride CH3SO2CI and tosyl chloride give low to moderate yields of ROCSO2CH3 and RC=CS02-Aryl. Part of the sulfonyl chloride reacts with the lithium alkynylide to give a chloroalkyne. A more succesful method to prepare acetylenic sulfones involves Oxidation of acetylene sulfides with peiacids. 

Cycloadducts with great synthetic potentialities have been easily obtained from the reactions of dienes with allenic sulfones (ArS02CH=C=CH2) and acetylenic sulfones (essentially ArSO,C=CH, but some disubstituted acetylenes (R S02C=C-R2) have been used). A few applications are briefly summarized in the following schemes. 

The capability of hydroxylamine derivatives to be either 0- or N-nucleophiles in the reactions with acetylenic compounds depends on the structure of the latter. For example, ALferf-butylhydroxylamine can add to acetylenic sulfones either by the nitrogen atom or by the oxygen atom, depending on the character of the substituent at the triple bond (Scheme 80) (74JOC2641). 

The zincation of the acetylenic sulfonate 35 furnishes an intermediate lithium alkynylzincate which undergoes a 1,2-migration of a methyl group, followed by a cyclization, leading to a cyclopropylidenylzinc derivative. This intermediate can then be quenched with an aldehyde, resulting in the allylic... 

Synthesis of (—)-Lasubine II. A reductive desulfonylation with lithium in ammonia is employed in the total synthesis of quinolizidine alkaloid (—)-lasubine II.264 A conjugate addition of methyl (.S )-(2-pipcridyl)acetate to an acetylenic sulfone, followed by lithium diisopropylamide (LDA)-promoted intramolecular acylation is the key step in the preparation of the quinolizine structure of (—)-lasubine II (Eq. 154). 

Sulfoxide, sulfinate and sulfonate are used as activators of acetylenic or vinyl units. Several a, P unsaturated synthons, namely acetylenic sulfoxide (1), vinyl sulfoxide (2), acetylenic sulfinate (3), acetylenic sulfonate (4), and l-propene-l,3-sultone (5) are developed. Their applications in Diels-Alder reactions, heterocycle and alkaloid syntheses are also investigated. For the chiral acetylenic sulfoxide, the sulfoxide moiety not only enables chemical activation of the acetylene unit, it can also induce stereochemical control at the adjacent carbon centers to achieve enantioselective synthesis. 

The first synthesis of acetylenic sulfonate 72 was achieved by MCPBA oxidation of sulfinate 68 a to 71, followed by potassium fluoride desilylation, in 90% overall yield. However, to our surprise, the triisopropylsilyl-protected acetylenic sulfinate 68 b resisted oxidation with the oxidants we tried, including MCPBA, oxone, H202/Se02, and Ru04 generated from RuCl3/NaI04 [37],... 

Acetylenic sulfonate 72 is relatively less stable and has to be stored at 0°C to avoid decomposition. The results of the Diels-Alder reaction of 72 are summarized in Table 8 [38]. For a reactive diene, such as cyclopentadiene, the cycloaddition took place readily at 0°C. For less reactive dienes, the reactions were carried out at elevated temperature. Mixtures of regioisomers resulted when unsymmetrical dienes were used. Sulfonate is a powerful electron-withdrawing group. Among the three acetylenic dienophiles (sulfoxide 1, sulfinate 68 d and sulfonate 72) we studied, the acetylenic sulfonate is the most reactive... 

Table 8. Diels-Alder reactions of acetylenic sulfonate 72...

The use of ethyldiazoacetate in the Pechmann pyrazole synthesis has been adapted for use on solid support. Treatment of solid-supported acetylenic sulfone 35 with an excess of EDAC, followed by cleavage from the solid support, provided 36 as a single regioisomer. Notably, when the reaction was done in solution phase with 37, the isomers 38 and 39 were isolated in a 4 1 ratio. 

The coupling of acetylenic iodides with copper sulfinates leads to the formation of uncommon acetylenic sulfones (Fig. 26). Sonication promotes this reaction, which can be made even easier by using a mixture of the sulfinic acid and commercial copper "carbonate" (a hydrated mixture of copper carbonate and hydroxide).i54 Successful results were also recorded in an extension using copper thiosulfonates and copper dimethyl phosphite. 

Similarly, Back and coworkers reported an increased regioselectivity in the reaction of ethyl diazoacetate with acetylenic sulfones 116 to yield the pyrazoles 117 and 118 (Scheme 6.27). In solution, the same acetylenic sulfone generated regioisomers in a 4 1 mixture, while a single regiosiomer was afforded on the solid support. Based on these results, it appears that the solid support is capable of directing the approach of the diazoacetate, perhaps due to steric effects. 

Scheme 6.27. Dipolar cycloadditions of acetylenic sulfones toward the synthesis of pyrazoles.

Acetylenic sulfones are reactive dipolarophiles. 1,3-Dipolar cycloaddition with nitrile oxide gave ester-linked isoxazoles (Scheme 11.47). However, the cycloadducts were cleaved from the resin with the sulfone moiety under alkaline hydrolysis. The method was applied later to the 1,3-dipolar cycloaddition reaction to prepare a wide selection of heterocycles, such as pyrroles, pyrazoles, 1,2,3-triazoles, and isoxazoles. " ... 

T. G. Back, H. Zhai, Cyclizations and cycloadditions of acetylenic sulfones on sohd supports. Chem. Commun. 2006, 326-328. 

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