Aldehydes cyanohydrin ethers

The Fisher oxazole synthesis involves condensation of equimolar amounts of aldehyde cyanohydrins (1) and aromatic aldehydes in dry ether in the presence of dry hydrochloric acid. ... 

The double process of cyanation/transcyanation of co-bromoaldehydes and racemic cyanohydrins as a source of HCN is a really interesting process (Scheme 10.25). Thus, using this reaction it is possible to obtain optically active (S)-ketone- and (R)-aldehyde-cyanohydrins in one pot [55], The reaction is carried out in diisopropyl ether using a crude extract of almond containing (R)-oxynitrilase as biocatalyst. The optically active (a-bromocyanohydrins prepared by this method is used as starting materials for the synthesis of valuable compounds such as... 

Acyloins.3 Grignard reagents of the type R1CH2MgX react with the O-tri-methylsilyl ethers of aldehyde cyanohydrins to form products that are hydrolyzed by acids to acyloins in 75-85% yield. 

Strecker reactions are among the most efficient methods of synthesis of a-amino nitriles, useful intermediates in the synthesis of amino acids [73] and nitrogen-containing heterocycles such as thiadiazoles, imidazoles, etc. [74]. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a source of cyano anion provides promising and safer routes to these compounds [73b,75]. TMSCN is, however, readily hydrolyzed in the presence of water, and it is necessary to perform the reactions under strictly anhydrous conditions. BusSnCN [76], on the other hand, is stable in water and a potential source of cyano anion, and it has been found that Strecker-type reactions of aldehydes, amines, and BuaSnCN proceed smoothly in the presence of a catalytic amoimt of Sc(OTf)3 in water [77]. No surfactant was needed in this reaction. The reaction was assumed to proceed via imine formation and successive cyanation (it was confirmed that imine formation was much faster than cyanohydrin ether formation under these reaction conditions) again the dehydration process (imine formation) proceeded smoothly in water. 

The preparations of hydroxypyrazines by primary syntheses have been described in Chapter II, and are summarized briefly, together with further data, as follows Section II.IG, from the reaction of a, 3-dicarbonyl compounds with ammonia [282 (cf. 281, 280), 283, 285] with additional information (1042, 1043) Section II.IM, from 1,2-dicarbonyl compounds with a-amino acids (311) Section II.IN, from a-amino acids through piperazine-2,5-diones (93,95,101,282,312,313)with additional data (843) Section 11.10, from aldehyde cyanohydrins ( ) [317-319 (cf. 282)1 and Section II.IP, from o-nitromandelonitrile and ethereal hydrogen cyanide (325). The preparations from a,iJ-dicarbonyl compounds with a,/ -diamino compounds are described in Section 11.2 (60, 80, 358, 359, 361-365b, 365d, 366-375) additional data have also been reported (824, 825, 827,845,846,971, 1044, 1045) and some reaction products have been isolated as the dihydro-pyrazines (340,341,357). 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

In catalytic processes with enzymes such as D-oxynitrilase and (R) xynitrilase (mandelonitrilase) or synthetic peptides such as cyclo[(5)-phenylalanyl-(5)-histidyl], or in reaction with TMS-CN pro-mot by chiral titanium(IV) reagents or with lanthanide trichlorides, hydrogen cyanide adds to numerous aldehydes to form optically active cyanohydrins. The optically active Lewis acids (8) can also be used as a catalyst. Cyanation of chiral cyclic acetals with TMS-CN in the presence of titanium(IV) chloride gives cyanohydrin ethers, which on hydrolysis lead to optically active cyanohydrins. An optically active cyanohyrMn can also be prepared from racemic RR C(OH)CN by complexation with bru-... 

The condensation of cyanohydrin ethers with aldehydes or ketones provides a-hydroxy ketones. 0-Benzoyl-protected cyanohydrins react with aldehydes to give a-hydroxy ketones via intramolecular deprotective benzoylation analogous to TMS-protect cyanohydrins (Scheme 10). ... 

Saturation of an equimolar mixture of aromatic aldehyde cyanohydrins and aromatic aldehydes in absolute ether at 0°C with dry hydrogen chloride results in the formation of 2,5-diaryloxazoles.114 116 The reaction often yields 2,5-diaryl-4-oxazolidones as by-products, and oxazolid-4-ones are the only products or major by-products if either of the starting materials is aliphatic. 

A number of methods for the generation of acyl anion equivalents from aldehydes have been developed. Related to the benzoin condensation, aldehyde cyanohydrins, protected as their ether derivatives, are readily transformed into anions by treatment with lithium diisopropylamide (LDA). Reaction with an alkyl halide gives the protected cyanohydrin of a ketone from which the ketone is liberated easily. Reaction with an aldehyde or ketone leads to the formation of an a-hydroxy ketone (1.109). ... 

Heteroatom-stabilized Carbanions. Heteroatom-stabilized and allylic carbanions serve as homoenolate anions and acyl anion equivalents, e.g. a-anions of protected cyanohydrins of aldehydes and Q ,/3-unsaturated aldehydes are intermediates in general syntheses of ketones and Q ,/3-unsaturated ketones (eq 36). Allylic anions of cyanohydrin ethers may be a-alkylated (eq 37) or, if warmed to —25°C, may undergo 1,3-silyl migration to cyanoenolates which may be trapped with TMSCl. Metalated Q -aminonitriles of aldehydes are used for the synthesis of ketones and enamines (eq 38). Similarly, allylic anions from 2-morpholino-3-alkenenitriles undergo predominantly a-C-alkyl-ation to give, after hydrolysis, a,/3-unsaturated ketones (eq 39). ... 

This form of protection is advantageous for aldehydes, because the trimethylsilyl cyanohydrin ethers of aldehydes present a reactive hydrogen atom on the a carbon. This hydrogen can be replaced with lithium, after which the compound may be converted to a ketone by reaction with an alkyl halide, or it may be converted to an a-hydroxyketone by reaction with another aldehyde or ketone (Scheme 4.4) ... 

Allylic ethers of aldehyde cyanohydrins have also been prepared under phase transfer conditions [23]. The organic phase, consisting of aldehyde cyanohydrin, an allylic halide (preferably the bromide) and dichloromethane is brought into contact with aqueous sodium hydroxide and tricaprylmethylammonium chloride. Anion exchange in the aqueous phase leads to the tricaprylmethylammonium/hydroxide ion pair, which reacts with the cyanohydrin to form the corresponding alkoxide. Reaction of the alkoxide with the allylic halide leads to the allylic ether of the cyanohydrin (Eq. 7.9). The formation of small amounts of allylic nitriles is apparently due to the side... 

The conversion of aldehydes to ketones can be accomplished by protecting the derived aldehyde cyanohydrin with ethyl vinyl ether and alkylating this species with lithium dlisopropylamlde and an alkyl halide following by deprotection. ... 

Conversion of aldehydes to ketones via cyanohydrin derivatives (ethers) by alkylation or Michael addition also used with sdyl ethers, dialtylamlnonitnies (see also Stetter reaction). 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

The in situ cyanosilylation of p-an1saldehyde is only one example of the reaction which can be applied to aldehydes and ketones in general. - The simplicity of this one-pot procedure coupled with the use of inexpensive reagents are important advantages over previous methods. The silylated cyanohydrins shown in the Table were prepared under conditions similar to those described here. Enolizable ketones and aldehydes have a tendency to produce silyl enol ethers as by-products in addition to the desired cyanohydrins. The... 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

In 1896, Emil Fisher found that 2,5-diphenyloxazole hydrochloride was precipitated by passing gaseous hydrogen chloride into an absolute ether solution of benzaldehyde and benzaldehyde cyanohydrin. The oxazole hydrochloride can be converted to the free base by addition of water or by boiling with alcohol. Many different aromatic aldehydes and cyanohydrin combinations have been converted to 2,5-diaryloxazoles 4 by this procedure in 80% yield. ... 

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