Lithium carbonylation

This rate expression is consistent with the reaction scheme shown in Eq. 10.6, formulated on the basis of the Krauss-Smith paper. Thus, the initially formed cuprate dimer/enone complex with lithium/carbonyl and copper/olefin coordinations [71, 72] transforms into the product via an intermediate or intermediates. A lithium/ carbonyl complex also forms, but this is a dead-end intermediate. Though detailed... 

The central feature of the mechanism is the 3-cuprio(III) enolate Cpop, of an open, dimeric nature, as shown by comparison of theory with experimentation involving NMR and KIEs [80, 81]. This species serves as the direct precursor to the product (Scheme 10.5, top box). In this critical CPop complex, copper/olefin (soft/soft) and a lithium/carbonyl (hard/hard) interactions are present. The open complex may be formed directly, by way of an open cluster (bottom left of Scheme 10.5), or by complexation of a closed cluster with the enone (CPcl). Experiments have shown that the enone/lithium complex (top left of Scheme 10.11) is a deadend species [60, 74]. 

Nonmetal Oxides. Molten lithium burns vigorously in C02 lithium carbonyl is formed with CO in liquid ammonia and reacts explosively with water or air silica or glass is rapidly attacked at 250°C.10... 

The models become more complex when they take the structure of the base into account. A simple and very popular hypothesis was proposed for esters by Ireland and coworkers in pioneering work23. This model supposes that a monomeric LDA is the active species and that the lithium-carbonyl interaction leads to a six-membered cyclic Zimmerman-Traxler chair-like transition state24, at which a more-or-less concerted proton transfer occurs. The resulting preference for the E enolate observed in THF and the Z preference in THF-HMPA mixtures, an issue discussed in more detail below, could even be accounted through steric considerations (Scheme 4). 

Carbon monoxide reacts with many metals to form metal carbonyls, some of which explode upon heating. Reactions with alkali metals yield the corresponding carbonyls, which explode on heating. Lithium carbonyl detonates when mixed with water, igniting gaseous products (Mellor 1946, Suppl. 1961). It undergoes violent reactions... 

Table 6 The distance (A) from lithium, carbonyl carbon (Cl and C4), and alkyl carbon (C2 and C3) of lithium aUtyl dicarbonates to the nearest graphite carbon.

Lithium aluminium hydride LiAlH is a useful and conveuient reagent for the selective reduction of the carbonyl group and of various other polar functional groups. It is obtained by treatment of finely powdered lithium hydride with an ethereal solution of anhydrous aluminium chloride ... 

After the umpolung of an aldehyde group by conversion to a l,3 dithian-2-ide anion (p. 17) it can be combined with a carbonyl group (D. Seebach, 1969, 1979 B.-T. GrO-bel, 1977 B). Analogous reagents are tosylmethyl isocyanide (TosMIC), which can be applied in the nucleophilic formylation of ketones (O.H. Oldenziel, 1974), and dichloromethyl lithium (G. KObrich, 1969 P. Blumbergs, 1972 H. Taguchi, 1973),... 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

Neither sodium borohydride nor lithium aluminum hydride reduces isolated carbon-carbon double bonds This makes possible the selective reduction of a carbonyl group m a molecule that contains both carbon-carbon and carbon-oxygen double bonds... 

The principal synthetic application of lithium dialkylcuprate reagents IS their reaction with a 3 unsatu rated carbonyl compounds Al kylation of the 3 carbon occurs... 

Lithium diisopropylamide is a strong enough base to abstract a proton from the a carbon atom of an ester but because it is so sterically hindered it does not add readily to the carbonyl group To illustrate... 

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

The carbonyl group of carbohydrates can be reduced to an alcohol function Typi cal procedures include catalytic hydrogenation and sodium borohydnde reduction Lithium aluminum hydride is not suitable because it is not compatible with the solvents (water alcohols) that are required to dissolve carbohydrates The products of carbohydrate reduc tion are called alditols Because these alditols lack a carbonyl group they are of course incapable of forming cyclic hemiacetals and exist exclusively m noncyclic forms... 

Lithium amides of primary / fZ-alkylamines yield N-(/ f2 -alkyl)-0-(/ f2 -butyl)hydroxylamines, whereas lithium amides of primary alkylamines yield A/-alkylbenzamides and LiOO—due to nucleophilic attack on the carbonyl group (245). 

A related but distinct rhodium-catalyzed methyl acetate carbonylation to acetic anhydride (134) was commercialized by Eastman in 1983. Anhydrous conditions necessary to the Eastman acetic anhydride process require important modifications (24) to the process, including introduction of hydrogen to maintain the active [Rhl2(CO)2] catalyst and addition of lithium cation to activate the alkyl methyl group of methyl acetate toward nucleophilic attack by iodide. 

High yields of optically active cyanohydrins have been prepared from hydrogen cyanide and carbonyl compounds using an enzyme as catalyst. Reduction of these optically active cyanohydrins with lithium aluminum hydride in ether affords the corresponding substituted, optically active ethanolamine (5) (see Alkanolamines). 

Many other organometaUic compounds also react with carbonyl groups. Lithium alkyls and aryls add to the ester carbonyl group to give either an alcohol or an olefin. Lithium dimethyl cuprate has been used to prepare ketones from esters (41). Tebbe s reagent, Cp2TiCH2AlCl(CH2)2, where Cp = clyclopentadienyl, and other metal carbene complexes can convert the C=0 of esters to C=CR2 (42,43). 

Earlier catalysts were based on cobalt, iron, and nickel. However, recent catalytic systems involve rhodium compounds promoted by methyl iodide and lithium iodide (48,49). Higher mol wt alkyl esters do not show any particular abiUty to undergo carbonylation to anhydrides. 

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