Thioacetal allylation

Apart from thioacetals, allyl sulfides are among the easiest sulfides to deprotonate and alkylate because of the conjugating ability of the allyl group. However, the very delocalization that assists anion formation means that the anions often react unregioselectively lithiated phenyl allyl sulfide, for instance, reacts with hexyl iodide to give a 3 1 ratio of regioisomers. 

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. 

The Pd-catalyzed allylic alkylation of thiocarboxylate ions was carried out with potassium thioacetate (KSAc) and potassium thiobenzoate (KSBz) and the racemic cyclic and acyclic carbonates rac-3aa, rac-3ba, rac-lda, rac-laa, rac-lba, and rac-lca, respectively (Scheme 2.1.4.21). The carbonates rac-3aa, rac-3ba, rac-lda, rac-laa, and rac-lba were treated with KSAc (1.4 equiv) or KSBz (2.0 equiv) in the presence of Pd(0)/L (2 mol%) and BPA (8 mol%) in CH2CI2/H2O. Under these conditions the acyclic carbonates rac-3aa and rac-3ba gave the thioesters 18aa, 18ab and 18ba, respectively (Table 2.1.4.14, entries 1-3), with high enantioselec-tivities in high yields [26]. 

Potassium nitrosodisulfonate, 258 Trimethylsilyl chlorochromate, 327 By hydrolysis of acetals or thioacetals Amberlyst ion-exchange resin, 152 Methylthiomethyl p-tolyl sulfone, 192 By isomerization of allylic alcohols N-Lithioethylenediamine, 157 By oxidation of aromatic side chains Trimethylsilyl chlorochromate, 327 From oxidative cleavage of alkenes [Bis(salicylidene-7-iminopropyl)-methylamine]cobalt(II)... 

Alcohols can be selectively oxidized in the precence of dithioacetals derived from unconjugated ketones.83,101 On the other hand, the thioacetals at benzylic and allylic positions can be hydrolyzed under very mild conditions with IBX in DMSO in the presence of traces of water.102... 

These thioacetals can be deprotonated by K2C03 in the presence of Aliquat 336 and the anions obtained react with various electrophiles including allylic halides. In contrast to reactions with NaH as the base, reaction with an allylic bromide results in allylic transposition. 

Treatment of the 2-pyrrolyl allyl thioether (498) with acetic anhydride and quinoline at 170 °C (or in A jV-dimethylaniline at ca. 100 °C) results in a thio-Claisen rearrangement to give the 5-(3-allyl-2-pyrrolyl) thioacetate (499), whilst peracid oxidation of (498) produces the non-rearranged sulfone in low yield and Raney nickel reduction of (498) yields 3-propylpyrrole (78CJC221). The polyphosphoric acid-catalyzed cyclization of (2-pyrrolylthio) acetic acid (501 R = R = H) somewhat unexpectedly yields (502) via the Spiro intermediate, instead of forming the expected oxothiolane (500), which can be obtained by a Dieckmann cyclization of ethyl (3-ethoxycarbonyl-2-pyrrolylthio) acetate (501 R = Et, R = C02Et) (B-77MI30506). 

This I04 -5i02 reagent is not very elective in the oxidation of sulfides into sulfoxides. However, sulfuryl chloride adsorbed wet silica gel is an excellent reagent for this transformatim (equation 5). High yields of methyl aryl, diaryl, allylic. benzylic and dialkyl sulfoxides are thus obtainable. The procedure commends itself by its simplicity and its extension to thioacetals provides a good, quantitative re-... 

The vinylogous thioacetal 33 was transformed into the a,(8-unsaturated ketone 34 upon CuOTf-mediated hydrolysis whereas the HgCl2-promoted reaction was less effective (Sch. 9) [27]. Similarly, vinyl sulfide 35, which bears an allylic alcohol, was converted into the aj3-unsaturated ketone 36 with complete regiocontrol [28]. This regioselectivity is not dependent upon the heteroatom because the vinyl ether 37 hydrolyzes to the aldehyde or ketone 38 [29]. 

In their synthesis of fukinone, Marshall and Cohen converted the known ene-ol (340) into (341) by acetylation, allylic oxidation, and conjugate methylation with dimethylcopperlithium. A Wolff-Kishner reduction of (341) followed by oxidation of the resultant alcohol and enol-acetylation yielded (342). The epoxide of (342) was thermolysed to give (343) which, on reaction with iso-propenyl-lithium and selective oxidation, gave the ketol (344) which was converted in two steps into fukinone (335). A number of sesquiterpenoids, e.g. fukinanolide (345), with the rearranged eremophilane skeleton viz. fukinane (346 R = Me) are known. Nay a and Kobayashi have now prepared this parent hydrocarbon by Raney nickel reduction of the thioacetal of fukinan-8-al (346 R = CHO). 

Nickel catalysts also catalyze Grignard substitution to allylic compounds including allyl alcohol [230-233] ethers [230,231,234,235 Eq. (106) 231] amines, albeit in a low product yield [231] sulfides [231,236,237], including thioacetals [238] thiols [231] selenides [239] carboxylates [240] phosphates [94,121] and halides [Eq. (107) 230], most likely via intermediate / -allyl-Ni species. Monosubstitution of bis-allyl ether was possible [Eq. (108) 235]. Most of the literatures cited in the foregoing disclosed regiochemical outcome associated with these allylic substitutions. 

Alkynylsilanes have been used as terminators in allylic alcohol and ketene thioacetal initiated cycliza-tions. In the late 1970s Heathcock and Johnson independently established the utility of alkynylsilanes in cyclization reactions. The example reported by Heathcock illustrated the electronic effect of silicon in the formic acid promoted transformation of the alkynylsilane (76) to the bicyclic ketone (78) in 76% yield. In contrast cyclization of the analogous alkyne (77) produced the bicyclo[2.2.2]octene (79), as illustrated in Scheme 38. 

Allylation of all these species is apparently less selective (Scheme 69, entry a), and among the various thioacetals tested 1,3-dithianes proved to be the ones which lead to the highest 0 7 The use of HMPA as a cosolvent was shown to have no effect on the regioselectivity of the allylation. However, both exclusive 7-allylation and 7-methylation have been achieved by performing the reaction in the presence of copper(I) iodide-trimethyl phosphite complex (Scheme 69, entries a-e). The reaction is best achieved with allylic chlorides, bromides and phosphate esters and does not occur with acetates, although these compounds usually react with cuprates. In all cases where isomers could be formed with respect to the electrophile, the ratio of 5n2 5n2 products was found to be greater than 0.67 (Scheme 69, entries b-e).- Related reactions have already been described with allylic sulfides (Scheme 27, see Section 1.3.2.2.4). 62.iM... 

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