Lithium iodide aldol reaction

Lithium Iodide. Lithium iodide [10377-51 -2/, Lil, is the most difficult lithium halide to prepare and has few appHcations. Aqueous solutions of the salt can be prepared by carehil neutralization of hydroiodic acid with lithium carbonate or lithium hydroxide. Concentration of the aqueous solution leads successively to the trihydrate [7790-22-9] dihydrate [17023-25-5] and monohydrate [17023-24 ] which melt congmendy at 75, 79, and 130°C, respectively. The anhydrous salt can be obtained by carehil removal of water under vacuum, but because of the strong tendency to oxidize and eliminate iodine which occurs on heating the salt ia air, it is often prepared from reactions of lithium metal or lithium hydride with iodine ia organic solvents. The salt is extremely soluble ia water (62.6 wt % at 25°C) (59) and the solutions have extremely low vapor pressures (60). Lithium iodide is used as an electrolyte ia selected lithium battery appHcations, where it is formed in situ from reaction of lithium metal with iodine. It can also be a component of low melting molten salts and as a catalyst ia aldol condensations. 

Triphenylphosphine-Diethyl azodicar-boxylate-Lithium halides, 332 Mukaiyama aldol reaction 1-Methoxy-l, 3-bis(trimethylsilyloxy)-l, 3-butadiene, 178 Tin(II) chloride, 298 Titanium(IV) chloride, 304 Trityl perchlorate, 339 Murahashi reaction N,N-Methylphenylaminotributylphos-phonium iodide, 191... 

McKervey and coworkers have used lithium iodide as a catalyst for mixed aldol reactions several examples are shown in equation (60). In all cases studied, 2-butanone reacts solely at C-1. The process is also applicable to other ketones, but they react much more slowly than do methyl ketones. For... 

The synthesis of the fragment C3-C13 was achieved in five steps from 169. Treatment of the tosylated stereotetrad 169 with 5 equivalents of lithium acetylide in DMSO led an acetylenic compound which was treated with ra-Buli and methyl iodide, and then reduced by Na/NH3 to produce the E-geometry of the C12-C13 double bond with concomitant removal of the PMB group at C5, giving the primary alcohol 170 (49% yield for the three-step sequence). Swern oxidation of 170 gave the corresponding aldehyde which was involved in an Evans-type asymmetric aldol reaction with the boron enolate A to produce the adduct 171 (dr > 95/5, 90% yield). (Scheme 33). 

Catalysed aerobic epoxidation of the styrene-cobalt complex, followed by the addition of trimethylsilyl isothiocyanate, yields 4-phenyloxazolidine-2-thione 123 <96TL7315>. The 4-substituted 2-oxazolidinone 124 undergoes a "chromium Reformatsky" reaction with aldehydes RCHO (R = i-Pr or Ph) in the presence of chromium(ll) chloride and lithium iodide to give mainly the unusual anti-aldol products 125 in excellent dia,stereomeric excess and yield <97TL4,387>. 

A key driver for the development of the DBR has been the increased availability of the requisite chromium carbene. Fischer carbenes undergo a wide variety of useful reactions and a significant effort has been devoted to their synthesis. These carbenes undergo many of the same reactions as esters. The a-hydrogens in 13 are quite acidic, with a pKa of approximately 8, that allows for application of the Aldol condensation to form the vinyl-substituted carbene 14. Of course, alkynes insert into these carbenes to form new vinyl substituted carbenes 15. However, the absence of a heteroatom on the carbene center makes these poor substrates for the DBR. The classical route to Fischer carbenes is the Fischer route addition of an organolithium to hexacarbonyl chromium and alkylation with a hard electrophile. Hoye has also shown that alkyl iodides under phase-transfer conditions can be used to alkylate the lithium alkoxide. Thus reaction of vinyl lithium 16 provides the carbene 17 in 53% over two steps. 

Aldol Reactions.—Anhydrous lithium iodide in ether is an effective reagent for the formation of a./S-unsaturated ketones via aldol condensations between ketones and aldehydes [equation (44)].In the presence of trimethylsilyl chloride and triethylamine, the aldol product is trapped as the silyl ether derivative, as a mixture of stereoisomers. 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

The chiral auxiliary is the oxazolidinone (24) derived from IS,2R) norephedrine. Acylation with propionyl chloride gives (25) and this is deprotonated to afford exclusively the internally chelated Z-enolate, which reacts with methallyl iodide from the face opposite the methyl and phenyl groups of the auxiliary. The product (26), a 97 3 mixture of diastereomers, is purified to a ratio of better than 500 1. Reductive removal of the auxiliary and careful oxidation of the primary alcohol under non-racemising conditions affords the chiral (5)-aldehyde (27). This in turn is reacted with the boron enolate of (25), which furnishes with remarkable selectivity the u aldol product (28). The reason for the choice of boron rather than lithium is to invert the facial selectivity of the reaction— the enolate is no longer constrained to be planar by internal chelation and rotates in order to place the bulky dibutyl borinyl group on the opposite side to the methyl and phenyl ... 

---