A-Arylaldehydes

In 2007, Li and List reported the asymmetric hydrogenation of a-arylaldehydes catalysed by [RuCl2(Xyl-BINAP)(DPEN)], providing the corresponding primary alcohols in excellent enantioselectivities and yields, as shown in Scheme 2.40. As an application of this reaction, the biologically active (5)-enantiomer of the non-steroidal anti-inflammatory drug, ibuprofen, could be... 

Metalated SAMP- or RAMP-hydrazones derived from alkyl- or arylethyl ketones 3 add to arylaldehydes both diastereo- and enantioselectively. Substituted / -hydroxy ketones with relative syn configuration of the major diastereomer are obtained with de 51-80% and 70-80% ee. However, recrystallization of the aldol adducts, followed by ozonolysis, furnishes diastereo- and enantiomerically pure (lS, S )-. yn-a-mcthyl-/3-hydroxy ketones 5 in 36-51% overall yield. The absolute configuration of the aldol adducts was established by X-ray crystallographic analysis. Starting from the SAMP- or RAMP-hydrazone either enantiomer, (S,S) or (R,R), is available using this methodology16. 

Protected cyanohydrins may be employed as acyl anion equivalents in 1,4-additions in the presence of HMPA129. For instance cyanohydrins prepared from arylaldehydes add in a 1,4-fashion under thermodynamic control (THF or THF/HMPA) to cyclohexenone, isophorone and decalone systems in the latter case c/.s-octahydro-2(l/f)-naphthalenones are exclusively obtained 130-131. 

Z- Configuration is typical of the majority of a-aryl(hetaryl)-/V-alkylaldo-nitrones. The isolation of -isomers in the condensation of aromatic aldehydes with iV-j3-]ihenyletli Tliydroxylamine has been described (155). The synthesis of a, N -diary lnitrones gives best results if acidic catalysis is employed (156), or when clay is used as a catalyst (157). Significant reduction of reaction time and increase in the yields of nitrones can be achieved if microwave irradiation is used (158, 159). On the basis of polymeric arylaldehydes, the synthesis of polymeric a,-diarylnitrones has been described (160). 

More recently, a new and straightforward one-pot approach was reported by Bu et al. <2003JOC5415>. This reaction involves the cyclocondensation of l,2-dipyridin-2-yl-ethane-l,2-dione 120 and arylaldehydes, in the presence of ammonium acetate. Imidazo[l,5- ]pyridines 121 were obtained in reasonable yields, but competitive formation of imidazoles 122 was observed. The amount of ammonium acetate used in this reaction was also shown to strongly influence the yield of the cyclization (Scheme 38). 

A versatile synthesis of triazolopyrazines has been elaborated by Akritopoulou-Zanze et al. <2004TL8439>. The method involves two steps a multicomponent Ugi reaction and a subsequent ring closure. Thus, arylaldehydes, propargylamine, cyclohexylisocyanide, and azidoacetic acid yielded the intermediate 406 which easily underwent cyclization to give the partially saturated derivative 407 in excellent yields. 

Stobbe was the first to observe photochromism in fulgides (1.33) when he synthesised them by the condensation of an arylaldehyde or ketone with a substituted methylene succinate. However, it was not until the 1970s, during the course of the extensive work carried out by Heller and his collaborators, that their chemistry and use in photochromism was truly exploited. Heller s work showed, amongst many other things, the importance of R in (1.33) being a 5-membered ring heterocycle, e.g. furan. 

Unlike the 13C-NMR method, H-NMR spectra are not applicable to 3-alkylaldehydes. For 3-arylaldehydes, the chemical shifts of 2-H, 3 -H, and 5-H appear deshielded in oxazolidines derived from chiral aldehydes with configuration A, where Rz is the aryl group. 

The apparent fickleness of the acyl-pyrroles and -indoles in their reaction with carbanions to form new C—C bonds arises from the contribution made by the zwitterionic structure, e.g. (410b), to the resonance hybrid and the choice of the reaction conditions is critical for a successful nucleophilic reaction. Thus, formyl-pyrroles and -indoles do not normally undergo the Cannizzaro reaction nor do they form stable cyanohydrins or undergo benzoin-type reactions. However, surprisingly, 2-formylpyrrole reacts with arylaldehydes in the presence of potassium cyanide to yield (428), which is easily oxidized to (429) (B-77MI30505). It is noteworthy that the presence of an ester substituent adjacent to the formyl group modifies the mesomeric interaction to such an extent to allow the formation of (430) in low yield, as a result of an initial benzoin-type self-condensation (Scheme 76) (68BSF637). 

Balan and Adolfsson [28] reported a direct catalytic enantioselective three-component aza Baylis-Hillman reaction between arylaldehydes, tosylamides, and Michael acceptors using the quinidine-based Hatekayama catalyst 96 [29] together with titanium isopropoxide as a Lewis acid cocatalyst (Scheme 9.18). High chemical yields and stereoselectivity ranging between 49 and 74% ee were obtained using various substituted arylaldehydes. 

Barbas and co-workers [31] have reported a related reaction of a trans-4-aryl-3-buten-2-one, an arylaldehyde, and Meldrum s acid in the presence of catalytic amounts of an amino acid forming spirotriones in good yields and ees (Scheme 9.21). Among a family of 19 pyrrolidine-based catalysts, 5,5-dimethyl thiazolidi-nium-4-carboxylate (DMTC) 113 was found to be the most efficient catalyst for this reaction. 

A catalytic enantioselective arylation of arylaldehydes employs a chiral /3-amino alcohol and a boronic acid-diethylzinc exchange reaction to generate the reactive arylzinc species.247... 

The mechanisms of asymmetric synthesis of aziridines from guanidinium ylides and arylaldehydes have been probed by varying para-substituents in the aldehyde.339 Hammett plots show a mechanistic switchover going from electron-donating to electron-withdrawing groups. 

A highly enantioselective proline-catalysed intramolecular Morita-Baylis-Hillman reaction of hept-2-enedial (111) has been reported. Addition of imidazole to the mixture resulted in an unusual inversion of enantioselectivity.149 The first example of a TiCU-mediated Morita-Baylis-Hillman-type reaction of cy-acetyl cyclic ketene dithioacetals with arylaldehydes has been described.150... 

S)-Proline also catalyzed Mannich reactions in a three-component (donor aldehyde, 4-methoxyaniline, arylaldehyde) protocol - that is, without preformation of imine (Table 2.14) [71b, 82]. (For experimental details see Chapter 14.2.2). This three-component format also afforded the syn-Mannich products in good yields with high diastereoselectivity and enantioselectivities when slow addition of donor aldehyde and/or formation of the imine prior to addition of donor aldehyde was used at a lower reaction temperature, such —20 °C. Reactivity of benzaldehyde and of N-PMP-imine of benzaldehyde as acceptors was compared in the... 

Alternatively, enantiomerically enriched 3-aryl-y-lactones have been synthesised using a Sml2-mediated carbonyl-alkene coupling between enantiomerically pure arylaldehyde-Cr(CO)3 complexes and ketones (Scheme 5.25). 

Emphasis on the employment of transition metal catalysts to achieve useful synthetic transformations is illustrated by three procedures in this volume. The reaction of allylic alcohols with aryl halides in the presence of a palladium derived catalyst can be used to prepare various /3-arylaldehydes. This is illustrated by the preparation of 2-METHYL-... 

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