ALLYLIC DITHIOACETALS

Nickel-Catalyzed Silylolefination of Allylic Dithioacetals (E,E)-Trimethyl(4-Phenyl-l,3-butadienylIsilane. 

Cross-coupling of allylic compounds occurs by transmetallation between 7i-allyl intermediates and organometallic compounds of Mg, Zn, B, Al, Si and Sn, and subsequent reductive elimination. Reaction of the allylic dithioacetal 180 with MeMgBr in the presence of an Ni catalyst affords alkenes 184 bearing a tert-butyl group [90]. In this reaction, generation of the 7i-allylnickel 181 by oxidative addition and subsequent transmetallation with MeMgBr afford 182. Then the methylated product 183 is formed by reductive elimination, and finally the dimethylated product 184 is formed by the sequence of similar reactions. 

Trimethylsilylbutadienes. These dienes can be obtained by reaction of this Grignard reagent (1) with allylic dithioacetals catalyzed by Cl2Ni[P(C6H5)3]2. 

Nickel-Catalyzed Geminal Dimethylation of Allylic Dithioacetals (E)-1 -Phenyl-3,3-dimethyl-1 -butene. 

Whereas free singlet carbenes are rather unselective with respect to formation of cyclopropane 22 or ylide 23 and the cyclopropane is favored under conditions that populate the triplet state of a carbene (see Section I.2.I.2.4.2.6.2.), the metal carbenes generated with copper or rhodium catalysts display a selectivity for functional groups which are more nucleophilic than a double bond. Thus, no cyclopropanes are obtained from dialkylallylamines allyl sulfides -allyl dithioacetals , and allyl selenides under carbenoid conditions (copper or rhodium catalysts). 

NICKEL-CATALYZED SILYLOLEFINATION OF ALLYLIC DITHIOACETALS (E,E)-TRIMETHYL(4-PHENYL-1,3-BUTADIENYL)SILANE (Silane, trimethyl (4-phenyl-1,3-butadienyl)-, (E,E)-)... 

NICKEL-CATALYZED SILYLOLEFIN-ATION OF ALLYLIC DITHIOACETALS (E,E)-TRIMETHYL(4-PHENYL-1.3-BUTADIENYL)SILANE... 

Reaction with Sulfur Compounds. In a similar coupling reaction to those of alkyl halides, (1) reacts in the presence of a nickel catalyst with allylic dithioacetals to yield l-(trimethylsilyl) butadienes (eq 8). ... 

Ni, Z.-J. Luch, T.-Y. Nickel-Catalyzed Silylolefination of Allylic Dithioacetals E, )-Trimethyl(4-pheny 1-1,3-butadienyl)silane OS, (1991), 70, 240. 

Yuan, T.-M. Luh, T.-Y. Nickel-Catalyzed, Geminal Dimethy-lation of Allylic Dithioacetals ( )-l-Phenyl-3,3-dimethyl-l-butene OS, (1996), 74, 187. 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

Dithioacetal monoxides undergo Michael addition to acrylonitrile. The addition products are easily converted into y-ketonitriles 382 (equation 221). Benzenesulphinyl allylic carbanions 383 derived from the corresponding allylic sulphoxides react selectively at the y-position with a variety of cycloalkenones to give the l,4-adducts " (equation 222). Recently, Nokami and coworkers have synthesized some prostaglandin analogues via a three-component coupling process involving 1,4-addition of phenylsul-phinyl allylic carbanion (equation 223) . ... 

Lewis acid-mediated ionization of acetals also generates electrophilic carbon intermediates that react readily with allylic stannanes.190 Dithioacetals can be activated by the sulfonium salt [(CH3)2SSCH3]+BF4,191... 

The above examples represent Jl-heteroaromatic annulation involving the reaction of allyl anions whose double bond is a part of the heterocyclic ring system (Scheme 1). The corresponding a-oxoketene dithioacetals (1,3-electrophilic component) were generally derived from nonheterocyclic carbonyl precursors. Alternatively the Jl-heteroaromatic annulation can also be employed to a-oxoketene dithioacetals derived from heterocyclic ketones (1,3-bielectrophile) and hetero/nonheteroallyl anions (1,3-binucleophile). These reactions are described below. 

Reaction of a Dithioacetal Derived from Indoxyl with Allyl and Stabilized Benzyl Anions... 

The a-oxoketene dithioacetal 6.40 is derived from indoxyl (l,2-dihydroindol-3-one), a heterocyclic carbonyl precursor, and its reaction with simple allyl anions will also yield the corresponding Jl-annulation product. Thus when 6.40 was reacted with allyl anions 65 the corresponding carbinol acetals 66 formed insitu underwent smooth BF3.Et20 assisted cyclization to afford the corresponding carbazoles 67 in high yields <99T11563>. 

The reaction of 6.36 with allyl and benzyl anions was examined with a view to develop an efficient method for the synthesis of phenanthridines and their benzo[/]-derivatives. The dithioacetal 6.36 when reacted with allyl anions yielded the corresponding... 

The reaction of methylenesulphones with allyl halides in the presence of quaternary ammonium salts produces the 1-allyl derivatives [52], unlike the corresponding reaction in the absence of the catalyst in which the SN- product is formed (Scheme 6.5). In contrast, alkylation of resonance stabilized anions derived from allyl sulphones produces complex mixtures [51] (Scheme 6.6). Encumbered allyl sulphones (e.g. 2-methylprop-2-enyl sulphones) tend to give the normal monoalkyl-ated products. Methylene groups, which are activated by two benzenesulphonyl substituents, are readily monoalkylated hydride reduction leads to the dithioacetal and subsequent hydrolysis affords the aldehyde [61]. 

The most popular method for generation of a-thio-carbanion (migration terminus) is direct lithiation (deprotonation) with alkyllithium or lithium amide. These deprotonation methods are widely applicable to various substrates, not only benzyl or allyl sulfides , but also dithioacetals 142 which form 143 (equation 83), and a phosphonate substituted system 144 which gives 145 (equation 84). ... 

Dithioacids themselves (R CSSH) could be prepared in about a 40-50% yield by addition of Grignard reagents to caibon disulfide in THF as the solvent, followed by acidification in the presence of ether or pentane [143], Hartke has reported that the yields of dithioacids could be improved by reverse addition of the Grignard reagent to carbon disulfide [144], a protocol previously used by Julia [145] in the preparation of dithioesters from allylic organometallics. A 70-80% yield of dithioacetic acid was thus achieved on a molar scale. 

Developments of such cross-coupling processes to dithioacetals were reported by Luh and reviewed [319]. They led to a variety of applications for carbon-carbon single and double bond formation. The gent-dialkylation of allylic and benzylic dithioacetals is a good example of their interest. 

The thiophilic addition of Grignard reagents was also carried out with S-allylic and propargylic dithioates. In these cases a [2, 3] sigmatropic rearrangement of the magnesiocarbanion occurred, and alkylation at sulfur yielded the dithioacetals of (i-unsaturated ketones [334] or of allenic ketones [335]. 

Methyl 3-hydroxybutanedithioate (R = Me) (0.6 g 4 mmol) was added dropwise to a solution of LDA (2 eq) in THF cooled at -78°C. The mixture was stirred for 20 min. The yellow dithioester colour disappeared. Allyl bromide (1 eq) was added. Stirring was maintained for 45 min. The solution was quenched by an aqueous solution of ammonium chloride. The mixture was partitioned between ether and brine. The organic layer was washed with brine, dried with magnesium sulfate and concentrated. The crude ketene dithioacetal was left at ambient temperature for X d to achieve the rearrangement. A yellow oil was isolated by flash chromatography (elution with a 90 10 mixture of cyclohexane/ethyl acetate), yield 74%, as a 90 10 syn/anti mixture of diastereoisomers. 

Dimethylthexylsilyl trifluorometh-anesulfonate, 74 using other methods Allyl chloroformate, 9 Benzyl trichloroacetimidate, 32 Bromodimethylborane, 47 Chloromethyl ethyl ether, 75 2,3-Dihydro-1,4-dioxin, 112 p-Methoxyphenol, 181 of aldehydes and ketones as acetals or dithioacetals... 

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