Aldehydes imino

By the condensation of a nitrile with a phenol or phenol ether in the presence of zinc chloride and hydrogen chloride a hydroxyaryl- or alkoxyaryl-ketone is produced. The procedure is termed the Hoesch reaction and is clearly an extension of the Gattermann aldehyde reaction (Section IV,121). The reaction gives the best results with polyhydric phenols and their ethers with simple monohydric phenols the imino ester hydrochloride is frequently the sole product for example ... 

Of all the methods described for the synthesis of thiazole compounds, the most efficient involves the condensation of equimolar parts of thiourea (103) and a-haloketones or aldehydes to yield the corresponding 2-aminothiazoles (104a) or their 2-imino-A-4-thiazoline tautomers (104b) with no by-products (Method A, Scheme 46). 

Thiazoline, trans-2-amino-4,5-dimethyl-synthesis, 6, 310 2-Thiazoline, 2-aryl-synthesis, 6, 307, 308, 309 2-Thiazoline, 2-arylamino-tautomerism, 6, 248 2-Thiazoline, 2-dialkylamino-synthesis, 6, 308 2-liiiazoline, 5-imino-synthesis, 5, 461 2-"niiazoline, 2-mercapto-hydrolysis, 6, 272 oxidation, 6, 272 synthesis, 6, 307 2-Thiazoline, 2-methyl-aldehyde synthesis from, 1, 469 2-Thiazoline, 2-methyl-acetylation, 6, 270 acylation, 6, 270 H NMR, 6, 243... 

The addition of isocyanides and azide to aldehyde-derived enamines has led to tetrazoles (533,536). On the other hand the vinylogous amide of acetoacetic ester and related compounds reacted with aldehydes, isocyanides and acids to give a-acylaminoamides (534). Iminopyrrolidones and imino-thiopyrrolidones were obtained from the addition of cyclohexylisocyanide and isocyanates or isothiocyanates to enamines (535). An interesting method for the formation of organophosphorus compounds is found in the reactions of imonium salts with dialkylphosphites (536). 

The observations that heteroaromatic amino compounds are not easily diazotized, are quite readily hydrolyzed,and often do not form Schiff bases with aldehydes have all been incorrectly interpreted as indications that these compounds exist principally in the imino form, whereas these observations can reasonably be attributed to the fact that the amino groups in compounds of the type of 4-aminopyridine are electron deficient as a result of the contribution of structures of type 36. ... 

Phenylcyclopent[c]azcpine (33a) and 6,7-fused cyclopentazepines 33b-d are formed in moderate yields in a one-pot, two-stage process involving initial condensation of triphenyl-[(l-phenylvinyl)imino]phosphoranes 32 with 6-(dimethylamino)fulvene-2-carbaldehyde (30), followed by an intramolecular aza-Wittig reaction of the iminophosphorane with the pendant aldehyde function.5 The method fails with the unsubstituted vinylphosphorane 32 (R1 = R2 = H). 

Enolates derived from various imino compounds have been sulfinylated in reactions analogous to those shown by equations (14) and (15). Some representative examples are shown in equations 16-18. Here again, these compounds have been utilized in asymmetric syntheses. Addition of sulfinate ester 19 to a THF suspension of a-lithio-N,N-dimethylhydrazones, derived from readily available hydrazones of aldehydes and ketones, leads to a-sulfinylhydrazones in good yield, e.g. 53 and 54 (equations 16 and 17)85,86. Compounds 53 and 54 were obtained in a 95/5 and 75/25 E/Z ratio, respectively. The epimer ratio of compound 53 was 55/45. Five other examples were reported with various E/Z and epimeric ratios. 

On the other hand, novel diastereomeric p-amino thiol ligands possessing an isoquinuclidine skeleton have been readily prepared by Hongo et al. via imino-Diels-Alder reactions.As shown in Scheme 3.15, when applied to the enantioselective addition of ZnEt2 to various aldehydes, one of these ligands afforded the products with high enantioselectivities of up to 94% ee. 

Synthesis of complex 1. The pentadentate salen catalyst 1 was synthesized as described (9). In short, the tosylated 2-[2-(2-methoxyethoxy)-ethoxy]-ethanol 2 (10) was reacted with 2,4-dihydroxybenzaldehyde 3 to yield 4-alkoxy salicylaldehyde 4 after chromatographic purification (eq. 1). Subsequent condensation of 4 with 1,3-diaminopropanol yielded water-soluble salen ligand 5 in sufficient purity and 89% yield (11). The formation of an azomethine bond is indicated by a shift of the NMR signal for the carbonyl carbon from 194.4 ppm in aldehyde 4 to 166.4 ppm for the imino carbon in 5. The pentadentate ligand 5 was then treated with copper(ll) acetate in methanol to obtain the dinuclear copper(ll) complex 1 as a green solid (eq. 2) (11). 

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

Instead of using an aldehyde for trapping the primarily formed enolate, there are also a few examples which involve an imino acceptor in the second anionic step. The Collin group used a lanthanide iodide-mediated reaction of a ketene silyl acetal... 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

Type D synthesis, where the 3,4-CN bond is being formed, involves the reaction of thiosemicarbazones of aldehydes, ketones, and esters 97 with 3,3-pentamethyleneoxaziridine 98 to afford 5-imino-3,3-pentamethylene-l,2,4-thiadi-azolidines 99 (Equation 27). yV-Acylthioureas also undergo this transformation but, whereas this reaction is fairly general for thiosemicarbazones, only acetyl and benzoyl thioureas give 1,2,4-thiadiazolidines <1996CHEC-II(4)307>. There have been no new reports of type D syntheses since the publication of CHEC-II(1996). 

Ytterbium triflate [Yb(OTf)3] combined with TMSG1 or TMSOTf are excellent reagents for the conversion of a-methyl styrene and tosyl-imines into homoallylic amides 32 (Equation (19)) (TMS = trimethylsilyl).29 These conditions produce the first examples of intermolecular imino-ene reactions with less reactive imines. Typically, glyoxalate imines are necessary. A comprehensive examination of the lanthanoid metal triflates was done and the activity was shown to directly correlate with the oxophilicity scale. The first report used preformed imines, and subsequently it was found that a three-component coupling reaction could be effected, bypassing the isolation of the intermediate imine.30 Particularly noteworthy was the successful participation of aliphatic aldehydes to yield homoallylic amines. 

The anomeric appendage of imino sugars has been exploited to generate mimics of glycoconjugates. An example is reported in Fig. 42 for the synthesis of nojirimycinyl C-(L)-serine 109,73 in which the ozonolysis of the allylic appendage generates the aldehydes 106, on which the aminoacidic moiety was inserted by Wittig-Horner reaction. 

The aldehyde (10 mmol) in MeCN (5 ml) is stirred with the imino ester (I0 mmol), anhydrous K2C03 (0.14 g) and TEBA-C1 (0.23 g, 1 mmol) in MeCN (10 ml) at room temperature until the mixture solidifies. HzO (60 ml) is added and the solid is separated, washed well with H20 and recrystallized (if the cyclic product does not solidify, the mixture is extracted with Et20 (2 x 25 ml). The combined extracts are washed with H20 (25 ml), dried (MgS04) and evaporated to yield the product). 

In contrast with the reactions of the imino esters, the aldol condensation of imino nitriles and aromatic aldehydes in dichloromethane produces azabutadienes (Scheme 6.17), with the Z-isomers predominating often to the exclusion of the E-isomers [43, 44], Yields generally tend to be at least 10% lower when the reaction is conducted in acetonitrile. 

Figure 3.17 Approach to the dynamic combinatorial modification of the TAR-binding aptamer. Left, italics The TAR RNA sequence. Left, bold The TAR-binding aptamer. Left, boxed The 2 -amino-2-deoxyuridine (U-NH ) for dynamic RNA modification. Left center Rb—Rd, the aldehyde library components. Right center Imino-linked DCL members. Right The selected nalidixic aldehyde appended to U-NH results in the TAR RNA-aptamer complex stabilization.

The TAR RNA target sequence, the 2 -amino RNA library and the appended aldehydes were subjected to the DCC SELEX system. The screen selected a 19-nt sequence with U-NH appended at position 9 and unmodified at positions 6 and 7 (Eig. 3.20). Importantly, it was shown that different sequences were identified when control selections were carried out in the absence of aldehydes, proving that the imino-conjugated nucleic acids are being selected. 

Reactions of the type in Eq. (42) have been achieved with aldehydes and ketones [Eq. (43)] (9, 19). None of the intermediates according to Eq. (42) was isolated. A [2 + 2]-cycloaddition (step a) probably occurs, since [2 + 2]-cycloadducts can be isolated from the reaction of imino-boranes and oxoalkanes in particular cases (Section VI,A). As far as alkynes are concerned, addition of oxo compounds proceeds in the presence of BFj as a catalyst, but without a break of the CC <7-bond [in analogy to step c in Eq. (42)] rather polar alkynes are needed [Eq. (44)] (78). 

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