Halides aldehyde derivatives

The presence of a halogen may indicate a haloid salt of a base, alky-l, alkylcue, or aryl halide, add halide, haloid derivative of an aldehyde or aad. Some substances, like mustard oils, amino- uilphonic atids and thioamides, contain both nitiogen and sulphur. 

V-Methyl-2-methyl-3-(benzotriazol-l-yl)propanamide (631), on treatment with two equivalents of butyllithium, forms a dianion that reacts with alkyl and benzyl halides, aldehydes, and ketones to give monosubstituted products (632) (Scheme 124). With ethyl / -toluate, however, a lactam (634) is formed. The alkylated derivatives (632) eliminate benzotriazole upon treatment with NaOEt to afford trisubstituted a,)8-unsaturated amides (633) <93JHC1261>. 

A similar result has been achieved using heterocyclic formamidine derivatives (Scheme 31) (81TL5119). In addition to alkyl halides, aldehydes were also suitable electrophiles in this reaction. 

These derivatives react with the type of carbon electrophiles we have already met such as alkyl halides, aldehydes and ketones, and epoxides to give 5, 6 and 7 respectively. 

Pyridine A-oxides are readily deprotonated at C(2) using LDA or -butyllithium as base in THF and the reagents thus produced react in the usual way in high yields with a variety of electrophiles including iodine, alkyl halides, aldehydes, and ketones < 1995J(P 1 )2503>. For example, -lithio derivative 361 can be generated and intercepted by various electrophiles, e.g., carbon dioxide, elementary sulfur, or cyclohexanone giving 362 note that the lithiation prefers the carbon to the oxide rather than that ortho to the chlorine. 

The aminoacyl anions can also be generated as stoichiometric reagents in the foim of lithium derivatives which are stable at -75 C and react with a variety of electrophiles, including alkyl halides, aldehydes and ketones (Scheme 2)/ ... 

Carbonyl insertion reactions are also carried out in the presence of pentacarbonyliron and are widely used for organic synthesis. Reaction of pentacarbonyliron with an organolithium followed by protonation gives an aldehyde derivative if a suitable alkyl halide is used in place of acid, a ketone is obtained (Scheme 10.5) [19]. 

This zinc-promoted reaction has been used with a variety of carbonyl compounds. Thus, the Luche conditions were applied in a synthesis of (-1-)-muscarine using an aldehyde derived from ethyl lactate [109]. Allyl halide condensation onto a-ketoamides of proline benzyl ester gave good diastereoselec-tivity when performed in the presence of zinc dust and pyridinium p-toluene-sulfonate in a water/THF mixture. In this way, a-hydroxy ketones were obtained with good enantioselectivity after removal of the chiral auxiliary [110]. Reactions of allyl bromide under the Luche conditions with y-aldo esters afforded y-hydroxy esters, which were converted in a one-pot reaction to y-allyl-y-butyro-lactones (Scheme 22) [111]. 

Conversion of alkyl halides to hydrazones. Primary and activated secondary alkyl halides react with this triflyl hydrazine and K2 CO3 (2 eq.) in acetonitrile to form acyl hydrazones of aldehydes and ketones, respectively. The reaction involves alkylation followed by elimination of HSO2CF3. Yields are high (80-90%) in the case of aldehyde derivatives, but they are lower in the case of ketone derivatives. 

The a-alkylation of amines is a valuable synthetic transformation. The amino group itself is not suflBciently activating to allow conversion of an a-methyl (R2N—Me) (or methylene) group into an alkali-metal salt (R2N—CH2—M), but certain derivatives of secondary amines can be converted into lithium salts with a strong base. The resulting a-amino-organolithium species react readily with alkyl halides, aldehydes, acid chlorides and other electrophiles. Successful results have been obtained with A -nitroso derivatives, various sterically hindered amides or for-mamidines. For example, dimethylamine can be converted into the amines 91 and 92 via the formamidine 90 (1.95). ... 

Methyl 3,6-dihydrobenzoate forms an enolate on treatment with lithium di-isopropylamide which, with primary halides, undergoes a high-yielding alkylation leading to cyclohexa-1,3-diene derivatives (143) such coupling reactions unfortunately fail, however, with secondary halides, aldehydes, and diphenyl disulphide. 

Applications Based on Deprotonation of Selenoketals R Se CHB — alkyl) and Seleno-orthoesters. Deprotonation, usually with KDA, of selenoketals (PhSe)2CHR (R = alkyl) gives carbanions that react efficiently with common electrophiles [primary alkyP - and benzyl halides, aldehydes, ketones, and (for R = alkyl or H) epoxides ]. A few of the resulting selenoketals have been hydrolysed under very mild conditions. Carbanions derived from selenoketals undergo intramolecular reactions [e.g. (49)] when appropriately substituted, and can be used in the synthesis of silyl enol ethers, e.g. (50). ... 

Tritio-denitration In the presence of azoisobutyronitrile as radical initiator, tri-n-butyltin tritide can tritio-denitrate secondary and tertiary nitro compounds to give the respective labeled derivatives. Primary nitro groups can only be denitrated if they are located adjacent to keto groups . The carbanion-stabilizing properties of nitro groups facilitate the introduction of electrophiles such as alkyl halides, aldehydes and ketones at the a-position. Furthermore, nitroolefins are excellent Michael acceptors as well as dienophiles, which enables the regioselective and chemoselective synthesis of a broad range of acyclic and... 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

Aldehydes can also be prepared by the carbonylation of aryl and alkenyl halides and triflate, and benzyl and allyl chlorides using tin hydride as a hydride source and Pd(PhjP)4 as a catalyst[377]. Hydrosilancs arc used as another hydride source[378]. The arenediazonium tetralluoroborate 515 is converted into a benzaldehyde derivative rapidly in a good yield by using Et ,SiH or PH MS as the hydride source[379]. 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Amino-5-nitrothiazole, on treatment with arenesulfonyl halides and dimethylformamide at 140 C, gives (5-nitro-2-thiazolyl)amidme (274) (Scheme 168) (507, 508). The condensation products of the reaction of 2-aminothiazole derivatives with various aldehydes are grouped in Tables... 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

Because enolate anions ffle sources of nucleophilic car bon, one potential use in organic synthesis is their- reaction with alkyl halides to give a-alkyl derivatives of aldehydes and ketones ... 

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