Acyl with metallates

Conjugated dienes, upon complexation with metal carbonyl complexes, are activated for Friedel-Crafts acylation reaction at the akyhc position. Such reactions are increasingly being used in the stereoselective synthesis of acylated dienes. Friedel-Crafts acetylation of... 

Mixed chloiide alkoxides aie prepared by reaction with acyl chlorides, metal chlorides, hydrogen chloride, or chlorine (64). 

Similar ester carboxylate group containing polymeric titanate esters are obtained by the reaction of titanoxanes with carboxyUc acids (26), by reaction of a tetraalkyl titanate with a carboxyUc acid and 1—2 moles of water (27), or by reacting a polymeric metal acylate with a higher boiling carboxyUc acid and removing the lower boiling carboxyUc acid by distillation (28). 

Mixed-Metal Systems. Mixed-metal systems, where a zirconium alkyl is formed and the alkyl group transferred to another metal, are a new apphcation of the hydrozirconation reaction. These systems offer the advantages of the easy formation of the Zr—alkyl as well as the versatiUty of alkyl—metal reagents. For example, Cp2ZrRCl (R = alkyl or alkenyl) reacts with AICI3 to give an Al—alkyl species which may then be acylated with... 

C-C bonds can be formed by reaction with alkyl iodides or more usefully by reaction with metal carbonyls to give aldehydes and ketones e.g. Ni(CO)4 reacts with LiR to form an unstable acyl nickel carbonyl complex which can be attacked by electrophiles such as H+ or R Br to give aldehydes or ketones by solvent-induced reductive elimination ... 

Acyl chlorides containing an a hydrogen are smoothly converted to alkenes, with loss of HCI and CO, on heating with chlorotris(triphenylphosphine)rhodium, with metallic platinum, or with certain other catalysts. The mechanism probably involves conversion of RCH2CH2COCI to RCH2CH2—RhCO(Ph3P)2Cl2 followed by a concerted syn elimination of Rh and H. See also 14-39 and 19-12. 

The mechanism of the condensation in Part D probably involves thioformylation of the metallated isocyanoacetate followed by intramolecular 1,1-addition of the tautomeric enethiol to the isonitrile. This thi2izole synthesis is analogous to the formation of oxazoles from acylation of metallated isonitriles with acid chlorides or anhydrides. " Interestingly, ethyl formate does not react with isocyanoacetate under the conditions of this procedure. Ethyl and methyl isocyanoacetate have been prepared in a similar manner by dehydration of the corresponding N-formylglycine esters with phosgene and trichloromethyl chloroformate, respectively. The phosphoryl chloride method described here was provided to the submitters by Professor U. Schollkopf and is based on the procedure of Bohme and Fuchs. The preparation of O-ethyl thioformate in Part C was developed from a report by Ohno, Koi/.uma, and Tsuchihaski. " ... 

Previous syntheses An example of this point can be recognized by examination of one known synthesis of thienobenzazepines (Scheme 6.1). This synthetic route involves a key palladinm-catalyzed cross-conpling of stannyl intermediate 3, prepared by method of Gronowitz et al., with 2-nitrobenzyl bromide. Acetal deprotection and reductive cyclization afforded the desired thienobenzazepine tricycle 4. In support of structure activity relationship studies, this intermediate was conveniently acylated with varions acyl chlorides to yield several biologically active componnds of structure type 5. While this synthetic approach does access intermediate 4 in relatively few synthetic transformations for stractnre activity relationship studies, this route is seemingly nnattractive for preparative scale requiring stoichiometric amounts of potentially toxic metals that are generally difficult to remove and present costly purification problems at the end of the synthesis. 

Azolides are also capable to acylate anionic metal carbonyl compounds. For instance, disodium tetracarbonylferrate as well as the corresponding ruthenium and osmium compounds can be formylated with formylimidazole in the presence of boric acid methyl ester ... 

Investigations in our laboratory by Rebecca Stimson have demonstrated that it is possible to combine the borane reduction of a metal acyl with the Lewis acid promoted CO insertion reaction which has been discussed earlier in this paper (29). In this reaction, which is presumed to proceed by equation 17, the... 

To replace the aforementioned acyl-main group and acyl-transition metal complexes, the natural course of events was to search for a stable and easy-to-handle acyl-metal complex that reacts as an unmasked acyl anion donor. Thus, the salient features of acylzirconocene chlorides as unmasked acyl anion donors remained to be explored. In the following, mostly carbon—carbon bond-forming reactions with carbon electrophiles using acylzirconocene chlorides as acyl group donors are described. 

Metallostannation often gives a better regio- and stereoselectivity than does hydrostannation, and the vinylmetal group that is formed can often react further with suitable electrophiles such as halogens, acids, alkyl halides, acyl halides, metal halides, aldehydes, or epoxides.110 ... 

The tetra-cA-cycIononatetracne 241 is unstable and easily rearranges at 23 °C (t /2 50 min) to the isomeric d.v-8,9-dihydroindcne 242 (equation 77)89. It is interesting, however, that the iron(III) tricarbonyl complex of tetraene 241 is stable for many days at room temperature and isomerizes to the Fe-complex of 242 only upon heating in octane at 101 °C89. The principle of stabilization of the reactive multiple bonds with metal carbonyl complexes is well-known in modem organic synthesis (e.g. see the acylation of enynes90). 

Other methods for preparing acyl complexes include the acylation of metallates and the treatment of alkyl carbonyl complexes with nucleophiles. 

In addition to the direct nucleophilic alkylation of carbonyl complexes, the acylation of metallates with, e.g., carboxylic acid chlorides [73,100,102] or anhydrides [79] is a practical way of generating acyl complexes (Figure 2.4). Illustrative examples are given in Table 2.3. 

Haloiminium salts can react with metallates or similarly nucleophilic transition metal complexes to yield heteroatom-substituted carbene complexes (Figure 2.7) [120]. This reaction is closely related to the acylation of metallates with derivatives of carboxylic acids (Section 2.1.1.2). Examples are given in Table 2.5. 

DKR of secondary alcohol is achieved by coupling enzyme-catalyzed resolution with metal-catalyzed racemization. For efficient DKR, these catalyhc reactions must be compatible with each other. In the case of DKR of secondary alcohol with the lipase-ruthenium combinahon, the use of a proper acyl donor (required for enzymatic reaction) is parhcularly crucial because metal catalyst can react with the acyl donor or its deacylated form. Popular vinyl acetate is incompatible with all the ruthenium complexes, while isopropenyl acetate can be used with most monomeric ruthenium complexes. p-Chlorophenyl acetate (PCPA) is the best acyl donor for use with dimeric ruthenium complex 1. On the other hand, reaction temperature is another crucial factor. Many enzymes lose their activities at elevated temperatures. Thus, the racemizahon catalyst should show good catalytic efficiency at room temperature to be combined with these enzymes. One representative example is subtilisin. This enzyme rapidly loses catalytic activities at elevated temperatures and gradually even at ambient temperature. It therefore is compatible with the racemization catalysts 6-9, showing good activities at ambient temperature. In case the racemization catalyst requires an elevated temperature, CALB is the best counterpart. 

Methyl acetate probably originates from the reaction of methanol with the intermediate cobalt-acyl complex. The reaction leading to the formation of acetaldehyde is not well understood. In Equation 8, is shown as the reducing agent however, metal carbonyl hydrides are known to react with metal acyl complexes (20-22). For example, Marko et al. has recently reported on the reaction of ri-butyryl- and isobutyrylcobalt tetracarbonyl complexes with HCo(CO) and ( ). They found that at 25 °C rate constants for the reactions with HCo(CO) are about 30 times larger than those with however, they observed that under hydroformylation conditions, reaction with H is the predominant pathway because of the greater concentration of H and the stronger temperature dependence of its rate constant. The same considerations apply in the case of reductive carbonylation. Additionally, we have found that CH C(0)Co(C0) L (L r PBu, ... 

Strong Brpnsted acids are also available to induce acylations.3,8,9 Perfluoroalkane-sulfonic acids were shown to be highly effective. Certain metal powders, such as Zn, Cu, Al, and Fe, were also found to effect acylations with acyl chlorides. The de facto catalysts are the in situ formed corresponding metal halides.3,8 A number of other catalysts were developed over the years however, many of these are effective only for the acylation of highly reactive aromatics, such as heterocycles.9... 

---