1,2-Allenyl sulfides

Allenyl sulfides RSCH=C=CH2 and the same nitrile oxide undergo cycloadditions which occur exclusively or predominantly at the external double bond to give 4-alkylidenedihydroisoxazoles 58 and 5-(methylthio)isoxazoles 59 (226). 

Another modification of the deprotonation/isomerization sequence starts with easily accessible 1-thio-substituted 1-propynes 303. Their deprotonation at the y-position generates allenyl anions that could be trapped regioselectively by different electrophiles R2X (Scheme 8.81) [167-169]. The resulting C-l-substituted allenyl sulfides 304 were obtained in high yields. 

Gasking and Whitham described the one-pot preparation of 1-silylated 3,3-di-methyl-substituted allenyl sulfides 307 (Scheme 8.82) [170]. Treatment of alkyne 305 with lithium thiolate generates allenyllithium species 306, which is subsequently silylated by trimethylsilyl chloride. Formation of lithiated intermediate 306 is based on a procedure developed by Clinet and Julia [171]. 

Cutting and Parsons described the transformation of acetylenic alcohols 314 into allenyl phenyl thioethers 316 by a two-step procedure (Scheme 8.85) [174], Deprotonation of alkynes 314 with n-butyllithium is followed by addition of phenylsulfenyl chloride, forming sulfenyloxy intermediates which subsequently rearrange to allenic sulfoxides 315. Treatment of allenes 315 with methyllithium results in loss of the sulfoxide moiety to form allenyl sulfides 316 in reasonable yields. 

Sulfur-containing acyclic and cyclic compounds have been prepared from allenyl sulfides in numerous transformations such as substitutions, additions, cydoaddi-tions and other cyclization reactions. Like the other donor-substituted allenes, allenyl sulfides are suitable substrates for regioselective lithiation and substitutions as exemplified in Scheme 8.86 [168, 169,175]. 

A stereoselective route to 2-(phenylthio)-l,3-butadienes such as 327 or 328 was developed by Pearson et al. [167] with allylboranes as crucial intermediates. Addition of 9-BBN to allenyl sulfide 324 gives the allylborane intermediate 325, which subsequently adds to aldehydes (Scheme 8.89). Typical of Peterson olefinations, this reaction can also be terminated by two different work-up procedures, either acidic conditions leading to anti-elimination, which affords Z-configuration of dienes 327, or basic work-up resulting in a syn-elimination to form (E)-dienes 328. 

Lewis acid-catalyzed ene reactions proceed between allenyl sulfides, e.g. 330, and aldehydes 329 to afford cis-trans mixtures of 1,3-butadienes 331 (Scheme 8.90) [168, 175b], Similar ene reactions observed with imines such as 332 provide the corresponding allylamines [168,177]. It was also found that the ene reaction of 1-silylated allenyl sulfide 333 with various aldehydes (or acetals) furnishes a,/l-unsaturatcd acyl compounds such as 334 and 335 under BF3-etherate catalysis [175b]. 

In contrast to the limited success with vinyl sulfides as components of [2 + 2] cycloadditions, allenyl sulfides show wide applicability. As illustrated in Scheme 8.91, Lewis acid-catalyzed [2 + 2] cycloadditions of l-trimethylsilyl-l-methylthio-1,2-propadiene (333) with a variety of electron-deficient olefins 336 provide cycloadducts 337 with excellent regioselectivity but with moderate stereoselectivity [175c], Nara-saka and co-workers reported the first Lewis acid-catalyzed asymmetric [2 + 2] cycloaddition of C-l-substituted allenyl sulfides 319 with a,/3-unsaturated compounds 338 using a chiral TADDOL-titanium catalyst. The corresponding cycloadducts 339 were obtained with 88-98% ee, but a low level of trans/cis selectivity (Scheme 8.92) [169,175d[. 

Tricyclic sulfur heterocycles 341 were prepared utilizing an intramolecular [4 + 2] cycloaddition. Heating of allenyl sulfides 340 to 110 °C leads to Diels-Alder products 341 in reasonable yields (Scheme 8.93) [163], Unfortunately, this method does not allow general access to these heterocycles, since a particular substitution pattern of the substrate is required. No reaction occurred with substrates lacking the thioacetal moiety. 

A similar ene-type reaction was also observed with 1,2-allenyl sulfides to afford 2-methylene-3-thio methylalk-3-enylamines [40]. 

A Ti-catalyzed enantioselective [2 + 2]-cycloaddition between allenyl sulfide 30 and 31 afforded the adduct with a high optical purity [27]. 

The reaction is of great value and most of the early work in the field is quoted and discussed in [203] by Block. As the allyl vinyl sulfide can be metallated and submitted to electrophilic substitution prior to rearrangement and the thiocarbonyl group hydrolysed in situ to a carbonyl group in the reaction product, the process has found considerable utility. The syntheses of propylure [488] and ris-jasmone [489] are early examples in which a thioaldehyde was intermediary formed (Y = H). A thioketone was involved [490] in the rearrangement of the allyl allenyl sulfide shown here. 

Scheme 3.57 Allenyl sulfides imination/sigmatropic rearrangement sequence.

Iodoalkylation of 1,2-allenyl sulfides or selenides, ArXCH=C=CH2 (X = S or Se), with I2 in MeCN-ROH (20 1) has been shown to afford (Z)-3-alkoxy-2-iodopropenyl (g) sulfides or selenides, ArXCH=C(I)-CH2OR, in high stereoselectivity and moderate to good yields.43... 

Allenyl sulfides have been converted into their a-lithio derivatives by deprotonation with n-BuLi in THF at —78 °C1092 or in the presence of TMEDA1093,1094. For example, compound 775 reacted with isobutylene oxide to give compound 776, after cyclization (Scheme 201). This dihydropyran 776 was transformed into atlantone 777, as a mixture of Z/E diastereomers, by treatment with HgCl2 in wet acetonitrile1092. 

Trisubstituted furans were obtained via an unprecedented 1,4-shift of the sulfanyl group of allenyl sulfides in high yields employing ruthenium complexes as catalyst, as depicted below. Furan products can also be provided in a one-pot reaction from a-diazocarbonyls and propargyl sulfide using both rhodium- and ruthenium-complexes or only a ruthenium-complex as catalyst <07AGE1905>. 

Employing this procedure, terminal and internal allenyl sulfides (18a-c) can be conveniently prepared via the copper salt catalyzed thermal decomposition of diazomalonates in acetylenic sulfides (16). The rearrangements are carried out in the absence of solvent by heating a mixture of methyl di-azomalonate and acetylenic sulfide 16 in the presence of catalytic amoimt of anhydrous cupric sulfate at 95-100 °C (Scheme 4) [15]. Similarly, the [2,3]sig-matropic rearrangement of sulfoniiun yhdes can be successfully applied to allenic systems, as demonstrated by the smooth conversion of allenic sulfide (19) into a 4 1 mixture of conjugated dienes (21a and 21b) (Scheme 4) [15]. 

Metallation of various 1-alkynyl sulfides, followed by alkylation of the resulting anion leads exclusively to a-alkylated allenyl sulfides (Scheme 39). 

Allenes The thiaphilic reaction of cuprate reagents on 2-alkynyl-l,3-dithiolanes gives allenyl sulfides. The residual sulfur substituent is replaceable by a Ni-catalyzed Grignard reaction. 

Introduction of an alkylthio group on the allene system increased the reactivity of the allene moiety in [2 + 2] cycloaddition reactions. It proved possible to conduct reactions of this allene at much lower temperatures. By adding Lewis acids, the reaction temperature could be decreased even more, as was illustrated by the Lewis acid catalyzed [2-1-2] cycioadditions of l-trimethylsilyl-l-methylthio-l,2-propadiene with a variety of electron-poor alkenes, including cyclic and non-cyclic enones, acrylates, methyl fumarate and acrylonitrile. When a chiral diol 21 based titanium catalyst was employed, the [2-1-2] cycloaddition reactions of /-acryloyl-l,3-oxazolidin-2-ones 17a and 17b with allenyl sulfides 18 yielded methylenecyclobutanes 19 and 20 with high optical purities (equation The highest yields were obtained with electron-poor allenophile 17b. 

Propynyl sulfides. A solution of 0.11 mol of butyllithium in 77 ml of hexane is added over 15 min to a mixture of 0.10 mol of the propynyl sulfide [6] and 80 ml of THF, while keeping the temperature at — 20 °C. After the addition the temperature is allowed to rise to 0 °C. A light-brown solution is formed which is assumed to contain about 0.10 mol of the lithiated allenyl sulfide. 

Thioallylation. Allylzirconium species derived from allenyl sulfides react with carbonyl compounds in an anri-selective fashion to give 4-hydroxy-3-sulfenyl-l-alkenes. 

Methyl allenyl sulfide (methylallenyl thioether) (20) Dipole moment 334,... 

A similar tendency was also found in the thermal reaction of propargyl phenyl sulfide. Thus, in the presence of cyclopentadiene on heating propargyl phenyl sulfide 53 in quinoline at 200 °C, thiachromen 56 and the Diels-Alder adduct 55 formed from allenyl sulfide 54 and cyclopentadiene were obtained [53]. In the absence of cyclopentadiene, a mixture of thiachromen 56 and thiacoumaren 57 was obtained. 

Tsutsumi K, Fujimoto K, Yabukami T, Kawase T, Morimoto T, Kakiuchi K. Palladium-catalyzed preparation of propargylic allenylic sulfides from propargyl halides or mesylates and thiols. Eur. J. Org. Chem. 2004 504-510. 

Catalysis of [2 + 2] Cycloadditions. EtAICI2 catalyzes a wide variety of [2 + 2] cycloadditions. These include the addition of alkynes or allenes to alkenes to give cyclobutenes and alkyli-denecyclobutanes (eq 14), the addition of electron-deficient alkenes to allenyl sulfides (eq 15), the addition of propiolate esters to monosubstituted and 1,2-disubstituted alkenes to form cyclobutene carboxylates (eq 16), and the addition of allenic esters to alkenes to form cyclobutanes. ... 

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