Organometallic acylation

The most complex example of this type of consecutive organometallic acylation, subsequent deprotonation, and tetrahydrofuran ring formation was recorded during the synthesis of the right hand portion of X-206 (Scheme 6). The high overall yield obtained in this process is a testament to the method s generality. 

Seebach has also studied the utility of esters in organometallic acylation. In this case, preformed ester enolates of 2,6-di(t-butyl)-4-methylphenyl esters (BHT esters) were slowly warmed above -20 C to form the corresponding ketene. If this was done in the presence of an ad tional equivalent of alkyl-lithium the ketene was trapped to give a ketone enolate in high yield. The same reaction failed to give any product when simple esters such as methyl, ethyl or Nbutyl were uscd. Scheme 17 is illustrative of the method. 

Thus far we have discussed numerous examples whereby selective ketone formation has been achieved through organometallic acylation. The problem was approached by choosing a less nucleophilic organometallic which can be acylated but does not interact wiA the desired product. Thus far, few reagents with this type of selectivity have been found (organocuprates). Most often, the strategy was to either preserve the tetrahedral intermediate formed upon nucleophilic addition or to activate the substrate... 

Acyl halides react with organometallic reagents without catalysts, but sometimes the Pd-catalyzed reactions give higher yields and selectivity than the Lincatalyzed reactions. Acyl halides react with Pd(0) to form the acylpalladium complexes 846, which undergo facile transmetallation. 

Ketones can be prepared by trapping (transmetallation) the acyl palladium intermediate 402 with organometallic reagents. The allylic chloride 400 is car-bonylated to give the mixed diallylic ketone 403 in the presence of allyltri-butylstannane (401) in moderate yields[256]. Alkenyl- and arylstannanes are also used for ketone synthesis from allylic chlorides[257,258]. Total syntheses of dendrolasin (404)f258] and manoalide[259] have been carried out employing this reaction. Similarly, formation of the ketone 406 takes place with the alkylzinc reagent 405[260],... 

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Similarly, 1-alkylpyrroles, indoles, furans, thiophenes [60], a-picoline [61], enols, malonates [76], and organometallic compounds [56, 62] react with acyl imines of trifluoropyruvates to give derivatives of a-trifluoromethyl a-amino acids... 

Phthalic anhydride also shows the ability to inhibit thermal destruction of polyolefins [21]. Among the organometallic compounds may be quoted organotin compounds R2Sr(OR )2, where R2 means alkyl, aryl, or cycloalkyl OR means alkoxyl, acyl, or R2Sn(CH2COORi)2, where Rj—Ci—Cm means alkyl, allyl, or benzyl Ro represents chloro-, mono-, or triorga-notin mercaptans [22,23]. 

Besides 1,3-oxathianes, the 1,3-dithiane 1-oxide moiety can be used for directing the nucleophilic addition of an organometallic reagent to a carbonyl group in a diastereoselective manner. The addition of methylmagnesium iodide to the 2-acyl-l,3-dithiane 1-oxide 23A leads exclusively to the diastereomer which is formed by Re-side attack. On the other hand, addition... 

Figure 6.48 Favored enantiomer in lipase-catalyzed acylations of racemic alcohols containing an organometallic substituent.

The wide substrate tolerance of lipases is demonstrated by the resolution of organometallic substrates [129-131]. The presence of tin, selenium, or tellurium in the structure of secondary alcohols does not inhibit the lipase activity and enantiopure organometallic alcohols were obtained by acylation in organic media (Figure 6.48). 

The Conversion of Acyl Halides to Ketones With Organometallic Compounds ... 

Reaction between acyl halides and organometallic compounds 10-115 Reaction between other acid derivatives and organometallic compounds... 

Halogenation of alkenyl organometallic compounds Addition of hydrogen halides to triple bonds Halogenation of alkynes or allenes Addition of alkyl halides to triple bonds Addition of acyl halides to triple bonds... 

The method is not restricted to secondary aryl alcohols and very good results were also obtained for secondary diols [39], a- and S-hydroxyalkylphosphonates [40], 2-hydroxyalkyl sulfones [41], allylic alcohols [42], S-halo alcohols [43], aromatic chlorohydrins [44], functionalized y-hydroxy amides [45], 1,2-diarylethanols [46], and primary amines [47]. Recently, the synthetic potential of this method was expanded by application of an air-stable and recyclable racemization catalyst that is applicable to alcohol DKR at room temperature [48]. The catalyst type is not limited to organometallic ruthenium compounds. Recent report indicates that the in situ racemization of amines with thiyl radicals can also be combined with enzymatic acylation of amines [49]. It is clear that, in the future, other types of catalytic racemization processes will be used together with enzymatic processes. 

Room temperature ionic liquids (RTILs), such as those based on A,A-dialkylimidazolium ions, are gaining importance (Bradley, 1999). The ionic liquids do not evaporate easily and thus there are no noxious fumes. They are also non-inflammable. Ionic liquids dissolve catalysts that are insoluble in conventional organic chemicals. IFP France has developed these solvents for dimerization, hydrogenation, isomerization, and hydroformylation reactions without conventional solvents. For butene dimerization a commercial process exists. RTILs form biphasic systems with the catalyst in the RTIL phase, which is immiscible with the reactants and products. This system is capable of being extended to a list of organometallic catalysts. Industrial Friedel-Crafts reactions, such as acylations, have been conducted and a fragrance molecule tra.seolide has been produced in 99% yield (Bradley, 1999). 

Organopalladium intermediates are also involved in the synthesis of ketones and other carbonyl compounds. These reactions involve acylpalladium intermediates, which can be made from acyl halides or by reaction of an organopalladium species with carbon monoxide. A second organic group, usually arising from any organometallic reagent, can then form a ketone. Alternatively, the acylpalladium intermediate may react with nucleophilic solvents such as alcohols to form esters. 

---