Transmetallation with Aluminum

Aluminacyclopentadiene as a metallole compound was not widely studied, and synthesis toward aluminacyclopentadiene via transmetallation of organolithium reagent and aluminum base compound was few. In 1977, Hoberg and 

So as to confirm whether the cyclopentadiene product was formed from the reaction of aldehydes with di-lithio compounds 1 or with aluminacyclopentadienes 52, in situ NMR experiment was carried out and 52 was observed in the NMR spectrum. Besides, 52 did not react with ketones. However, in contrast, di-lithio reagents could react with ketones to form cyclopentadienes. When 52 was formed at room temperature, no 2,5-dihydrofuran derivatives were generated in the presence of excess aldehydes. Moreover, the reactivity of aluminacyclopentadienes 52 with DMAD was further explored to give benzene derivatives 53 in moderate isolated yields. 

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The aldehyde homoenolate synthons discussed above do not add to aldehydes with a high degree of stereoselectivity. However, transmetalation to aluminum or titanium... 

An interesting metal effect was observed in the aldol condensations of the enolate derived from the iron acetyl complex (r)"-C HdFe(CO)(PPhd(COMe) with aldehydes [56,57]. Although the lithium enolate did not show any selectivity, the corresponding aluminum enolate by transmetalation with Et.AlCl exhibited exceptionally high diastereoselectivity (>99% de). The resultant P-hydroxy acyl complexes are transformed to P-hydroxy acids on decomplexation with Br.. 

Organoaluminum sonochemistry is not yet well developed despite the synthetic and economic interest. Aluminum, a ductile metal, is easily activated by sonication, as evidenced by the use of foils to determine the energy of cleaning baths. Alkyl halides react with aluminum at room temperature in THF to give the sesquihalide, reduced to the trialkyl compound in the presence of magnesium. Examples are known with bromomethane or -ethane.1 2,183 reaction occurs with stirring under similar conditions. Triethylaluminum was used in sonochemical transmetallation reactions leading to zinc and boron alkyls (Eq. 38). 

Therefore, the first step should proceed through a syn carbometallation to generate the cyclopropyliron species 138. The following step would be the (1-carbon elimination reaction keeping the cis-relationship between R and R, providing an iron enolate intermediate 137. Then, a transmetallation with an alkylaluminum species would generate the aluminum enolate 135, which would result, upon aqueous quench, in the corresponding tetrasubstituted alkene. Previous studies revealed that some neutral chromium(III) complexes are active in alkene polymerization... 

The auxiliaries R) and (S)-triphenylglycol 172 were also applied to achieve anti-selective propionate aldol additions, as shown by Braun and coworkers. It turned out that, for this purpose, the tertiary hydroxyl group of the propionate (R)-204 had to be protected by silylation. This was easily accomplished by a one-pot procedure that delivered the ester (R)-205. After deprotonation with LICA, the lithium enolate was transmetallated with dichloro(dicyclopentadienyl)zirconium and reacted with aliphatic aldehydes to give predominantly anti-diastereomers 206, the diastereomeric ratio surpassing 95 5. Reduction with lithium aluminum hydride finally led to diols 207 under the release of the chiral auxiliary R)-172. After its removal by chromatography, diastereomerically pure diols 207 were isolated with >95% ee (Scheme 4.45) [107]. For the benzaldehyde adduct 206 (R = Ph), alkaline hydrolysis was also performed and found to lead to epimerization to only a small degree. 

After a transmetalation with Zn(0Ac)2, Pd-catalyzed cross-coupling reactions with various aryl iodides or bromides furnish the polyfunctional biaryls 26-28 in 78-92% yield (Scheme 1). Interestingly, 10 mol% of Ga also catalyzes the aluminum insertion and 1-naphthyl iodide (29) reacts neat at 120°C with Al powder furnishing the 1-naphthylaluminium derivative 30 in >95% yield. Its reaction in toluene with an acid chloride leads to the desired ketone 31 in 96% yield [Eq.(8)] [13]. 

The insertion reaction can also be extended to benzylic chlorides. Thus, the reaction of the benzylic chloride 33 with Al dust in the presence of 3% InCls in THF at 20°C for 7 h furnishes the corresponding aluminum reagent 34. Transmetalation with Zn(OAc)2 followed by a copper(I)-catalyzed allylation with ethyl (2-bromomethyl)acrylate leads to the substituted acrylate 35 in 76% yield [Eq. (10)1 [14]. 

Transmetalation to give l-methyl-2-propenylaluminum followed by isomerization to 2-butenyl isomers may be involved in reactions between aldehydes and 2-butenyl(tributyl)-stannane induced by aluminum(III) chloride in the presence of one mole equivalent of 2-propanol. Benzaldehyde and reactive, unhindered, aliphatic aldehydes give rise to the formation of linear homoallyl alcohols, whereas branched products are obtained with less reactive, more hindered, aldehydes66,79. 

Transmetalation of lithium enolate 1 a (M = Li ) by treatment with tin(II) chloride at — 42 °C generates the tin enolate that reacts with prostereogenic aldehydes at — 78 °C to preferentially produce the opposite aldol diastereomer 3. Diastereoselectivities of this process may be as high as 97 3. This reaction appears to require less exacting conditions since similar results are obtained if one or two equivalents of tin(ll) chloride arc used. The somewhat less reactive tin enolate requires a temperature of —42 C for the reaction to proceed at an acceptable rate. The steric requirements of the tin chloride counterion are probably less than those of the diethyla-luminum ion (vide supra), which has led to the suggestion26 44 that the chair-like transition state I is preferentially adopted26 44. This is consistent with the observed diastereoselective production of aldol product 3, which is of opposite configuration at the / -carbon to the major product obtained from aluminum enolates. 

Transmetalation of 19 by treatment with two equivalents of diethylaluminum chloride generates the aluminum enolate species 23. The latter reacts with acetaldehyde to produce the stable aluminum aldolates 24 which do not undergo the Peterson elimination23. A protic quench then provides the a-silylated aldol adducts of tentative structures (2 R)-25 and (2 V)-25 with little diastereoselectivity. Other diastereomers are not observed. 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

In the following year, this method was also applied to the total synthesis of tjipanazole FI (371) (784). For this synthesis, the required bisindole 1444 was obtained starting from 5-chloroindole (1440) in three steps and 47% overall yield. Acylation of 1440 with oxalyl chloride led to the glyoxylic acid chloride 1441. Transmetalation of indolylmagnesium bromide with zinc chloride, followed by addition of the acid chloride, provided the ot-diketone 1443. Exhaustive reduction of 1443 with lithium aluminum hydride (LiAlFl4) afforded the corresponding bisindolylethane 1444. Executing a similar reaction sequence as shown for the synthesis of tjipanazole F2 (372) (see Scheme 5.243), the chloroindoline (+ )-1445 was transformed to tjipanazole FI (371) in two steps and 50% overall yield (784) (Scheme 5.244). 

The other commercially important routes to alkyltin chloride intermediates utilize an indirect method having a tetraalkyltin intermediate. Tetraalkyltins are made by transmetallation of stannic chloride with a metal alkyl where the metal is typically magnesium or aluminum. Subsequent redistribution reactions with additional stannic chloride yield the desired mixture of monoalkyltin trichloride and dialkyltin dichloride. Both -butyltin and /z-octyltin intermediates are manufactured by one of these schemes. 

Many other types of organometallics which are not acylated directly acid chlorides and which do not undergo addition to ketones may still transmetallate into the acylpalladiumfll) complex. Simple alkyl organomercurials have been acylated in this fashion to give moderate to good yields of ketones. " Larock has studied the palladium-catalyzed acylation of vinylmercury(II) compounds with acyl halides (equation 104). The reaction was only modestly productive and could not compare to the yield provided by aluminum chloride catalysis. 

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