Cyanohydrin ethers anion

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. 

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). ... 

An interesting development in the lithiated cyanohydrin ether approach to acyl carbanion equivalents involves the [2,3] sigmatropic rearrangement of the anions derived from allyl- or propargyl-cyanohydrin ethers/ Scheme 2 shows an example of the application of this process in the synthesis of y-dicarbonyl compounds or their monoenol ethers. ... 

Butadienyl sulphoxides act as excellent Michael acceptors for nucleophilic acylating agents, particularly lithiated cyanohydrin ethers." The resulting allylic anions may be alkylated, and simple hydrolyses complete an efficient synthesis of dienones [equation (30)]. 

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 2000, Kagan and Holmes reported that the mono-lithium salt 10 of (R)- or (S)-BINOL catalyzes the addition of TMS-CN to aldehydes (Scheme 6.8) [52]. The mechanism of this reaction is believed to involve addition of the BI NO Late anion to TMS-CN to yield an activated hypervalent silicon intermediate. With aromatic aldehydes the corresponding cyanohydrin-TMS ethers were obtained with up to 59% ee at a loading of only 1 mol% of the remarkably simple and readily available catalyst. Among the aliphatic aldehydes tested cyclohexane carbaldehyde gave the best ee (30%). In a subsequent publication the same authors reported that the salen mono-lithium salt 11 catalyzes the same transformation with even higher enantioselectivity (up to 97% Scheme 6.8) [53], The only disadvantage of this remarkably simple and efficient system for asymmetric hydrocyanation of aromatic aldehydes seems to be the very pronounced (and hardly predictable) dependence of enantioselectivity on substitution pattern. Furthermore, aliphatic aldehydes seem not to be favorable substrates. 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves9 and by the addition of hydrogen cyanide to silyl enol ethers.10 Sllylated cyanohydrins have proved to be quite useful 1n a variety of synthetic transformations, including the regiospecific protection of p-quinones,11 as Intermediates in an efficient synthesis of a-aminomethyl alcohols,6 and for the preparation of ketone cyanohydrins themselves.1 The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as acyl anion equivalents, providing general syntheses of ketones13 and acyloins.1 ... 

OL-Keto esters. The cyanohydrin silyl ether < 1) of methyl glyoxylate (4, 542-543 5, 720) can be converted by alkylation of the anion into the enol acetate (2) of a-keto esters. 

A nice example of the solvent-dependent dual reactivity of an electrophilic crypto-cationic species has been given by Hiinig et al. [663]. Ambident electrophilic a-enones react with nucleophiles such as the anion of the benzaldehyde O-(trimethylsilyl)-cyanohydrin (Nu ) in diethyl ether exclusively by 1,4-addition. In tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME), the 1,2-adduct is formed predominantly on the addition of HMPT or [12]crown-4 it is formed exclusively cf. Eq. (5-133). 

Synthesis of ketones. Stork and Maldonado have disclosed a new synthesis of ketones from aldehydes RCHO- RCOR. The aldehyde is first converted into the cyanohydrin and then the hydroxyl group is protected by reaction with ethyl vinyl ether to give (1). This is then converted into the anion by reaction with lithium diiso-propylamide under carefully controlled conditions. The base is generated from butyl-lithium and diisopropylamine in THF and then (1) in hexamethylphosphorie triamide... 

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. - - ... 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

If X in Scheme 41 represents a cyanide group (X = CN) the rearrangement of the anion leads to a cyanohydrin anion as the product, which can yield a carbonyl function directly.The reaction is not only known for allylic ethers but also for propargylic ethers, giving access to allenic carbonyl compounds in the latter case (equation 39). ... 

Allenic products ate formed in the anion-initiated rearrangement of cyanohydrin propargylic ethers (148 Table 10).- The intermediate cyanohydrins (149) are converted to allenyl ketones (150) upon work-up. 

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