Organometallic compounds with acid derivatives

With the usual reaction of organometallic reagents with acid derivatives (ester or acid chloride), the starting materials can add two equivalents of organometallic compound. The ketone generated after the first addition is quite reactive, and there is quite no selectivity between it and the starting acid derivative ... 

C. Reaction of Organometallic Compounds with Sulphurous Acid Derivatives... 

Acetylene is a Brpnsted acid (pA), 25). Its chemistry is associated with its triple-bond character and the labile hydrogen atoms. It can easily lose one proton to form the acetylide monoanion HC=C-(IUPAC name acetylenide) or release two to give the acetylide dianion C=C (C22-, IUPAC name acetylenedi-ide). The acetylenide H-C=C and substituted derivatives R-C=C- form organometallic compounds with the alkali metals. In these compounds, the interactions of the n orbitals of the C=C fragment with metal orbitals may lead to many structural types, e.g.,... 

The uncatalysed reaction of diisocyanates with polyols does not have any significance in the formation of polyurethanes. Reactions are catalysed by acids and organic bases. Among the good catalysts are tertiary amines and organometallic compounds, mainly tin derivatives. 

Since thiols are acid compounds (hydrosulfuric acid derivatives), mercaptides can also be obtained by reacting them with organometallic compounds [Clegg et al., 1995 Anderson et al 2003] ... 

Dicobalt-hexacarbonyl-alkyne complexes are another class of organometallic compounds with good stability imder physiological conditions. Complexation of the alkyne proceeds smoothly under mild conditions by reaction with Co2(CO)g imder loss of two molecules of CO [79]. The applicability of this reaction to peptides was shown by Jaouen and coworkers by the reaction of Co2(CO)g with protected 2-amino-4-hexynoic acid (Aha) and dipeptides thereof (Boc-Phe-Aha-OMe and Ac-Aha-Phe-OMe) [80]. Similarly, Cp2Mo2(CO)4 complexes of these alkynes were obtained. It has been shown that the C-terminal Met" in SP can be replaced by isostere analogs without appreciable loss of physiological activity. The same is true for the C-terminal Met in neurokinin A (NKA), another tachykinin peptide hormone (Scheme 5.16). Alkyne analogs of SP and NKA were obtained by replacement of these methionines with norleucine acetylene residues. Alternatively, Lys in NKA may be replaced by an alkyne derivative which can also be complexed to Co2(CO)g as shown in Scheme 5.16. Complexation with Co2(CO)g proceeds smoothly in about 50% yield for all derivatives [81]. After HPLC purification, these cobalt alkyne peptides were comprehensively characterized spectroscopically. Most notably, they exhibit typical IR absorptions for the metal carbonyl moieties between 2000-2100 cm [3]. Recently, there is renewed interest in Co2(CO)5(alkyne) complexes because of their cytotoxicity [82-84]. 

The carbonyl group of acid derivatives reacts with the nucleophilic carbanion available from organo-metallic reagents. However, the reactions of the individual classes of compounds are not as straightforward as the addition reactions of organometallic compounds with aldehydes and ketones. Addition of a carbanion to the acyl carbon atom generates a tetrahedral intermediate that can decompose to give a ketone that will react further with another equivalent of the carbanion. 

The most general synthetic route to ketones uses the reaction of carboxylic acids (or their derivatives) or nitriles with organometallic compounds (M.J. Jorgenson, 1970). Lithium car-boxylates react with organolithium compounds to give stable gem-diolates, which are decom-... 

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... 

The experimental conditions for the syntheses starting from acid chlorides of hydroxamic acids and from nitrile oxides are somewhat different. In the former case the other component of the reaction is organometallic, usually an organomagnesium derivative of an acetylene or, less frequently, a sodium enolate of a /8-diketone. Nitrile oxides condense directly with unsaturated compounds. 

II c., Cl 0 M L- X c Reaction of acyl halides or other acid derivatives with organometallic compounds... 

Acylation is one of the most fundamental and useful reactions in organic synthesis and is normally achieved by the reaction either with carboxylic acid derivatives and organometallic compounds or with masked acyl anions and aUcyl halides. 

Markl, Lieb and Merz have described the carbanionic addition of lithium or magnesium organometallic compounds to the P atom of 2.4.6-triphenyl-X -phos-phorins, which form deep red s ts 143. These can be alkylated either at the P atom to form X -phosphorins 144 or at C—2 to yield 1,2-dihydro-X -phosphorins 145. Acylation with benzoylchloride affords the 1,4-dihydro-X -phosphorin derivatives 146. Addition of acids or water leads to the synthetically important intermediates 147 which can be reconverted to the X -phosphorin-salts 143 by 2 N NaOH. 

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