Aldehydes directed syntheses

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 practice, the condensation of nitroalkane (60) and aldehyde (59) gives nitro lactone (57) directly. Synthesis ... 

The hydrosilylation of carbonyl compounds by EtjSiH catalysed by the copper NHC complexes 65 and 66-67 constitutes a convenient method for the direct synthesis of silyl-protected alcohols (silyl ethers). The catalysts can be generated in situ from the corresponding imidazolium salts, base and CuCl or [Cu(MeCN) ]X", respectively. The catalytic reactions usually occur at room tanperature in THE with very good conversions and exhibit good functional group tolerance. Complex 66, which is more active than 65, allows the reactions to be run under lower silane loadings and is preferred for the hydrosilylation of hindered ketones. The wide scope of application of the copper catalyst [dialkyl-, arylalkyl-ketones, aldehydes (even enoUsable) and esters] is evident from some examples compiled in Table 2.3 [51-53],... 

In the synthesis of AG5473/5507 (324/325) by Guo et al., many attempts were made to homologate an aldehyde directly through an intermediate acyliminium ion, but without success [68], Finally, a less direct route involving the addition of pro-pargylsilane to 321 afforded the allene 322 with 10 1 diastereoselectivity (Scheme 19.59). Allene 322 was then ozonized to give aldehyde 323 in 90% yield. 

Alkenylthiophenes and alkenylbenzo[6]thiophenes are most readily obtained by dehydration of the corresponding alkanols, obtained by reduction of the appropriate acyl derivatives (equation 12 Sections 3.14.2.4, 3.15.9.2.3). Allyl derivatives can be obtained by coupling a suitable allyl halide with the appropriate thienyllithium derivatives (Section 3.14.2.4). An unusual direct synthesis of 3-vinylthiophenes by ring closure of a-mercapto-aldehydes or -ketones with 1,3-butadienyl-l-triphenylphosphonium salts (386) gives satisfactory yields (equation 13) (75CJC3526). 

A number of syntheses have been proposed, mainly from a-chlorosulfides and alcohols or from 0,0-acetals or 5,5-acetals. Many references on these methods are to be found in a paper dealing with a direct synthesis of 0,5-acetals from aldehydes [56],... 

The direct synthesis of (a-hydroxyalkyl)trialkylsilane by a nucleophilic addition of a trialkylsilyl anion to an aldehyde or a ketone has not been readily accomplished because of the difficulty in the preparation of trialkylsilyl anions. Tin-mediated reverse Brook... 

The availability of amino-substituted furazans, both by direct synthesis from aminogly-oximes and via Hofmann degradation of the corresponding carboxamides, allows urea, thiourea, imino and acylamido derivatives, for example, to be prepared by reaction with isocyanates, isothiocyanates, aldehydes and acyl halides, respectively (73JPR791, 77JCS(P1)1616). Alkoxy and acyloxy derivatives are likewise formed from hydroxyfurazans (79JHC689). 

In 1992, Goodwin and Lynn reported the first example of template-directed synthesis of DNA analogs via formation of a reversible imino linkage [21]. Five years later, Hue and Lehn described the first use of the reaction of imine condensation for the selection, by DCC, of carbonic anhydrase inhibitors from a library of amines and aldehydes [8], Upon addition of the enzyme, the formation of one library component was strongly amplified when compared to a similar reaction carried out in the absence of template. Since then, imine exchange reaction has been applied... 

The value of the Amdt-Eistert method in synthesis rests with the versatility of the products obtained, and there have been a number of developments which increase the overall appeal. One of these allows the direct synthesis of homologous aldehydes by the reduction of the A -methylanilide with lithium aluminum hydride, or the thiol ester using Raney nickel (Scheme 9). ... 

An interesting reaction discovered by Wakamatsu involves the cobalt-catalyzed carbonylation of aldehydes in the presence of primary amides to give A-acylamino acids in high yield (equation 26). By combining this reaction with known catalytic routes to aldehydes, for example isomerization of allyl alcohols or hydroformylation of alkenes, it is possible to achieve the direct synthesis of A-acylamino acids from precursors other than aldehydes. ... 

The Mannich and related reactions provide one of the most fundamental and useful methods for the synthesis of y -amino ketones and esters [46]. Although the classical protocols include some severe side reactions, new modifications using preformed iminium salts and imines have improved the process. Some of these materials are, however, unstable and difficult to isolate, and deaminations of the products that occur under the reaction conditions still remain as problems. The direct synthesis of /5-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view [47, 48]. Our working hypothesis is that aldehydes could react with amines in the hydrophobic micellar system in the presence of a catalytic amount of lanthanide triflate and a surfactant to produce imines, which could react with hydrophobic silyl enolates [49]. 

A direct synthesis of the aromatic aldehydes by means of the Friedel-Crafts reaction could not be brought about until recently, because of the instability of formyl chloride, which, if formed, decomposes immediately into carbon monoxide and hydrochloric add ... 

Oxidation of benzyl ketone hydrazones with Hg2 (O2CCF3) in ether or dioxane gives a direct synthesis of phenylacetyl-enes (CeHsC CR). Olefin formation occurs with saturated aldehydes and carboxylic acids when they are allowed to react with ruthenium and rhodium complexes. Olefins can be converted to aldehydes in high yields by ozonization followed by treatment with dimethylsulfide. ... 

Phthalans (1,3-dihydroisobenzofuran) can be obtained by the reduction of phthalides. A direct synthesis of the phthalans can be achieved by lithiation of aromatic benzyl alcohols followed by treatment with an aldehyde or a ketone. This is illustrated below... 

The most direct synthesis of 1,4-dihydropyridines (7b) utilizes a procedure with either <5 + 1>, <3 + 2+1), or <2 + 1 + 2 + (1)> fragment combination. The latter represents the widely used classical Hantzsch s synthesis, which combines two molecules of an active a-methylenic carbonyl compound, an aldehyde, and an ammonia source (Scheme 3). 

As mentioned in Sect. 2.3, Inanaga and co-workers have demonstrated that Barbier-type reactions of organic halides with carbonyl compounds are promoted by addition of HMPA [16]. They reported a mild convenient method for the direct synthesis of lactones from bromo esters and ketones or aldehydes by using a HMPA-promoted Barbier-type reaction with Sml2 (Scheme 13). They also found that the SmI2/THF-HMPA system was highly useful for the generation of... 

A direct synthesis of chiral propargylic alcohols from 1-alkynes and aldehydes in the presence of Zn(OTf)2, EtjN, and (+)-A-methylephedrine has a broad scope. Several new ligands are found suitable for inducing asymmetric addition of R2Zn (mostly diethylzinc) to aldehydes. These include 42, 43, 44, 45, and Other (3-amino alcohols that show desirable features are S-ew-morpholinoisoborneol, which is more stable in air than the dimethylamino analogue, (S)-2-(pyrrolidin-l-yl)-l,2,2-triph-enylethanol, and a polymer-supported A-alkyl-a,a-diphenyl-L-prolinols. A,A-Dibutyl-norephedrine is useful in a solvent-free reaction. ... 

Much attention has been devoted to the conversion of aldehydes into the trimethylsilyl ethers of (a-hydroxyalkyl)-phosphonic acids 210 or analogous -phosphinic acids, or of the corresponding (a-hydroxyalkyl)phosphonic diamides 211 by the use of dialkyl trimethylsilyl phosphite or Me3SiOP(NEt2)2 (or other phosphorodiamidite) It is a reaction which occurs very readily, even at room temperature, and the ready methanolytic or hydrolytic removal of the silyl protecting group makes the procedure an attractive alternative to the direct synthesis of the (a-hydroxyalkyl)phosphonic acids from dialkyl hydrogenphosphonates and carbonyl compounds. Silyl-protected hydroxy-phosphonic and -phosphinic acid derivatives are useful for further synthetic development. ... 

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