Dithianes, allylation

In ( )-[2-(l-propenyl)-l, 3-dithian-2-yl]lithium, no problem of EjZ selectivity arises. It is easily prepared by deprotonation of the allylic dithiane87,88 with butyllithium in THF, whereas deprotonation of the 2-propylidene-l, 3-dithiane requires the assistance of HMPA. The addition to saturated aldehydes proceeds with excellent y-regioseleetivity and anti selectivity88,89. As often observed in similar cases, aldehydes which bear an, p2-carbon atom adjacent to the carbonyl group give lower selectivities. The stereoselectivity decreases with ketones (2-bu-tanone y/a 84 16, antiisyn 77 23)88. The reaction with ethyl 2-oxopropanoate is merely nonstereoselective90, but addition of zinc chloride improved the syn/anti ratio to 96 4, leading to an efficient synthesis of ( )-crobarbatic acid. 

To the best of our knowledge, the allylation of dithianes has not been previously reported in the literature. A range of dithianes underwent smooth allylation to give the desired thioester products in good yield however, a slightly increased catalyst loading (2-10 mol%) was needed (Table 8). 

Krabbe SW, Spafford MJ, Mohan RS (2010) Bismuth(in) triflate catalyzed allylation of cyclic acetals and dithianes followed by in situ derivatization to generate highly functionalized esters. Org Prep Proced Int 42 363-371... 

Lithiation of 2-propenyl-l,3-dithiane generates an allylic anion which reacts with active ketones at the side-chain carbon. The reaction was highly diastereoselective (96 4) and the product was obtained in 85% yield (Equation 58) <1996JOC1473>. 

A total synthesis of ( )-aromatin has utilized the lithium anion of the dithiane of (E)-2-methyl-2-butenal as a functional equivalent of the thermodynamic enolate of methyl ethyl ketone in an aprotic Michael addition (Scheme 189) (81JOC825). Reaction of the lithium anion (805) with 2-methyl-2-cyclopentenone followed by alkylation of the ketone enolate as its copper salt with allyl bromide delivered (807). Ozonolysis afforded a tricarbonyl which cyclized with alkali to the aldol product (808). Additional steps utilizing conventional chemistry converted (808) into ( )-aromatin (809). 

Carbon nucleophiles which do not readily trigger the rearrangement of epoxides include lithiated dithianes [295, 304], lithiated sulfones [238], lithiated diarylphos-phine oxides [240, 305], lithium enolates [306], and allylic organolithium or organo-magnesium compounds [298, 307-310] (Scheme4.67). 

The tolerance of the RCM reaction to diverse functional groups is illustrated by the synthesis of 14-membered macrocycles monocillin I and radicicol, reported by Danishefsky and coworkers [63]. In the presence of catalyst G2, cyclization of dienic substrates 90 and 91, which comprise an allylic epoxide and a ketone function protected as a dithiane, occurs in 55-60% yields, generating intermediate macrocy-clic dienes 92 and 93 of 6E,ttZ stereochemistry (Scheme 2.36). It is interesting to... 

Notes Jsyn-2-allyl-2-propionyl-1, 3-dithiane 1-oxide isolated (78%). 6Uncyclized haloalkylated material isolated (64%). 

All types of electrophiles have been used with 2-lithio-l,3-dithiane derivatives, including alkyl halides, sulfonates, sulfates, allylic alcohols, arene-metal complexes, epoxides, aziridines, carbonyl compounds, imines, Michael-acceptors, carbon dioxide, acyl chlorides, esters and lactones, amides, nitriles, isocyanates, disulfides and chlorotrialkylsilanes or stannanes. The final deprotection of the dithioacetal moiety can be carried out by means of different types of reagents in order to regenerate the carbonyl group by heavy metal coordination, alkylation and oxidation184 or it can be reduced to a methylene group with Raney-nickel, sodium or LiAIII4. 

The /-/ -bcnzcncmolybdcnum tricarbonyl complex 187 also suffered nucleophilic addition of 2-lithio-l,3-dithiane or its 2-methyl derivative at — 78 °C to give the ry -cyclohexadienyl anionic complexes 188, which were trapped with allylic bromides to yield, after CO insertion under CO pressure, trans-5,6-disubstituted 1,3-cyclohexadiene derivatives 189 (Scheme 55)253. Analogous reactions with [( 6-benzene)Cr(CO)3] give directly the corresponding cyclohexadiene in which the CO has been inserted in the allyl group. 

Scheme 16.11 shows the completion of the total synthesis of azaspiracid-1, which followed with slight modifications, the synthesis of the originally proposed structure of azaspiracid-1 (la). This chemistry was also carried out with the corresponding ABCD enantiomer in similar yields. Thns, lithiation of dithiane 51 (n-BuLi n-BnjMg) followed by addition into pentafluorophenol ester 68 resulted in CJ-C27 ketone 69 (50% yield). Ketone 69 was then elaborated into diacetate 70, this time as the TBS ether at C-25, as this protecting group was easier to remove than the acetate used in the earlier work directed toward the original stractnre (see Scheme 16.8). Stille coupling of this allylic acetate (70) then proceeded smoothly, as before, affording the complete Cj-C q backbone 71, which was successfully elaborated to the correct structure of azaspiracid-1 (1), identical in all measured physical properties ( H NMR, C NMR, Rf, [aj ) to the natural material.

Synthesis of P,y-unsnturated aldehydes. Treatment of the allylic bromide (1) with 1.3-dithiane gives the sulfonium bromide (2) in high yield. Treatment of (2) at -78° in THF with -butyllithium gives the ylide (3), which rearranges when warmed to 20°... 

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