Condensation trimethylsilyl chloride

Merck s thienamycin synthesis commences with mono (V-silylation of dibenzyl aspartate (13, Scheme 2), the bis(benzyl) ester of aspartic acid (12). Thus, treatment of a cooled (0°C) solution of 13 in ether with trimethylsilyl chloride and triethylamine, followed by filtration to remove the triethylamine hydrochloride by-product, provides 11. When 11 is exposed to the action of one equivalent of tm-butylmagnesium chloride, the active hydrogen attached to nitrogen is removed, and the resultant anion spontaneously condenses with the electrophilic ester carbonyl four atoms away. After hydrolysis of the reaction mixture with 2 n HC1 saturated with ammonium chloride, enantiomerically pure azetidinone ester 10 is formed in 65-70% yield from 13. Although it is conceivable that... 

Due to the high a-C,H acidity in the alkoxyethylidene complexes 6 (e.g.,piCa=8 (R=Me)) [ 16], transformations via an enolate analog are possible and have been used to introduce additional functionality into the carbene side chain to access various Fischer carbene complexes [3]. The a,/J-unsaturated complex 8 could be obtained from 6 (R=Et) by an aldol-type condensation with benzaldehyde 7 in the presence of triethylamine and trimethylsilyl chloride (Scheme 2) [17]. This reaction proceeds completely diastereoselectively to yield only the trans-isomer. Analogously, binuclear complexes have been prepared from 6 and 1,3-and 1,4-phthaldialdehyde in good yields [17]. This type of condensation has... 

A typical example for a type A reaction is the halosilane condensation", i.e. the reaction of the betaines I with trimethylsilyl derivatives with liberation of trimethylsilyl chloride. This reaction is especially smooth with Xc ... 

An interesting example of an application of this method pertains to the synthesis of pharmacologically active synthetic A1 -tetrahydrocannabinoids 134) of the type 267 which have a lipophilic tertiary alkyl side-chain. Equation 84 shows that organo-titanium chemistry provides a versatile means to prepare the precursors 264 (65-80 %)133). Demethylation of 264 using trimethylsilyl chloride and sodium iodide affords the resorcinol derivatives 265 ( 95%)133>. Compounds of this type have been previously condensed with 266 in the presence of acids to form the A1(6)-isomers of 267, which in turn can be converted into 267135). It should be mentioned that the meta-substitution pattern of 265 prohibits simple Friedel-Crafts alkylation of resorcinol, which is the reason why alternative multistep syntheses of 264 have had to be developed l34 136>. 

Intramolecular acyloin condensation [71] of the diester 90 under dilution conditions with sodium in toluene and with addition of trimethylsilyl chloride led to the bis(trimethylsilyl)en-diol ether 91 (29% yield) which was transformed subsequently in several steps to [l.l.l.ljparacyclophane 92 [71a]. 

Anion (64) generally reacts with carbonyl compounds at the y-position, whereas it reacts with alkyl halides at the a-position. The triethylaluminum ate complex of (64) exhibits reversed regioselectivity propanal and 2-methylpropanal give exclusively the a-adducts. The anti isomers are produced predominantly. Organic halides and trimethylsilyl chloride do not react with the aluminum ate complex. 9,11-Dodecadien-l-yl acetate, a pheromone of Diparopsis castanea, is prepared by condensation of 9-oxonon-l-yl acetate via the ate complex (Scheme 43). 

A parallel solid-phase synthesis of l,3,4-thiadiazolium-2-aminides involves trimethylsilyl chloride mediated cyclization of resin bound aldehydes 269 and 1,4,-disubstituted thiosemi-carbazides 268 <04JCO746>. Two additional combinatorial approaches have been developed to prepare focused libraries of 1,3,4-thiadiazoles <0478627 04BBR1053>. 1,3,4-Thiadiazoles 273 are prepared by condensation of triazole 271 with various carboxylic acids 272 in the presence of phosphorus oxychloride <04IJHC69>. 

Reaction of an ester enolate with an acid chloride will also generate a (3-keto-ester and is a useful alternative to the Claisen condensation. Ketone enolates can also be condensed with acid chlorides. An ester enolate can be trapped with trimethylsilyl chloride, as with aldehydes and ketones. An interesting variation of this... 

The reaction of the ester 51 with MeLi (55) in the presence of trimethylsilyl chloride cannot be performed on a large scale in a reproducibly high yield. For the synthesis of the Ci8-ketone 51 on a large scale, an alternative, a three-step route is used (Scheme 18). First the geranylacetone (52J is coupled in an Horner-Emmons reaction with diethyl cyano-methylphosphonate (4) with NaH as a base. Reduction of the nitrile by DEB AH then gives the aldehyde 56 in 73% yield. Aldol condensation of 56 with acetone (57) in the presence of a... 

Condensations of amines with 1-chlorocycloheptene in the presence of the complex base , sodamide and sodium t-butoxide, gave mixtures of enamines and cyclo-hepta-1,2-diene dimer. Excess n-butyl-lithium has been used to convert vinyl and aryl bromides into organolithium compounds which undergo useful reactions with, for example, benzophenone, dimethyl disulphide, diphenyl disulphide, trimethylsilyl chloride, and methyl iodide. Hence 1-bromo-cis-cyclononene was converted into 1-methylthio-cis-cyclononene via 1-lithio-cis-cyclononene the 1-methylthio... 

A rather similar method based on reductive alkylation of urea involves the use of trimethylsilyl chloride (TMSCl) as the catalyst in the condensation step and again utilizes sodium borohydride as the reducing agent [792]. Under these conditions, the parent urea can be converted into monosubstituted as well as disubstituted ureas in yields of 60-92%. 

Attempted acyloin condensations of the keto-diesters (232) in the presence of trimethylsilyl chloride gave products of transannular cyclization (233). ... 

In an extension of known methodology, Conia et al. have shown that ketones can be expanded by one carbon to 2-methylenones [i.e. (228) - (229)] by the addition of chloro(methyl) carbene to the trimethylsilyl enol ether derived from (228), followed by elimination of trimethylsilyl chloride. A somewhat related approach can be used to ring-expand the acyloin condensation products (230) to 1,3-diones (231). ... 

Aldol Reactions.—Anhydrous lithium iodide in ether is an effective reagent for the formation of a./S-unsaturated ketones via aldol condensations between ketones and aldehydes [equation (44)].In the presence of trimethylsilyl chloride and triethylamine, the aldol product is trapped as the silyl ether derivative, as a mixture of stereoisomers. 

Two derivatives of 15 have been produced via the acyloin condensation of diesters. Unfortunately the acyloin condensation works very poorly for the diesters in Chart 2 and even in the presence of trimethylsilyl chloride pure acyloin condensation products could not be isolated. The spectra of semidiones 3 and 15b... 

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