A-aryl aldehydes

Synthesis of aryl ketones or aldehydes from aryl tnllates or iodides and organo stannanes in ihe presence of CO and a palladum catalyst... 

Another arylation reaction which uses arenediazonium salts as reagents and is catalyzed by copper should be discussed in this section on Meerwein reactions. It is the Beech reaction (Scheme 10-49) in which ketoximes such as formaldoxime (10.13, R=H), acetaldoxime (10.13, R=CH3), and other ketoximes with aliphatic residues R are arylated (Beech, 1954). The primary products are arylated oximes (10.14) yielding a-arylated aldehydes (10.15, R=H) or ketones (10.15, R=alkyl). Obviously the C=N group of these oximes reacts like a C = C group in classical Meerwein reactions. It is interesting that the addition of some sodium sulfite is necessary for the Beech reaction (0.1 to 0.2 equivalent of CuS04 and 0.03 equivalent of Na2S03). 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

Scheidt reports using an amended Rokita method in conjunction with an umpolung derivative of several aryl aldehydes for the synthesis of a-aryl ketones.7 The procedure is indeed useful for the synthesis of 2-arylated benzofurans as shown by the synthesis of demethylmoracin I (Fig. 4.8). 

Decarbonylation is also observed upon photolysis of / ,y-unsaturated homoconjugated aldehydes and a-aryl aldehydes. For example, R-laurolenal produces two enantiomeric products in yields of 88% and 12%, respectively ... 

Table 4.8. Some Photodecarbonylation Quantum Yields for a-Aryl Aldehydes...

The photodecarbonylation of a-aryl aldehydes has been studied as a function of structure by Kuntzel, Wolf, and Schaffner<70) ... 

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). 

This method is of quite general applicability and the carbonyl compound may be an aldehyde, a ketone, or an ester. Similarly, the halide may be chloride, bromide, or iodide although yields are generally lower with iodides. Alkyl and aryl halides react with equal facility and the alkyl halide may be primary, secondary, or tertiary. A few examples of the yields obtained with a variety of reagents are given in Table I (the yields quoted are obtained by g.l.c. analysis of the reaction mixture using an internal standard ). 

Akiyama et al. disclosed an asymmetric hydrophosphonylation in 2005 (Scheme 32) [55], Addition of diisopropyl phosphite (85a) to A-arylated aldimines 86 in the presence of BINOL phosphate (R)-M (10 mol%, R = 3,5-(CF3)j-C Hj) afforded a-amino phosphonates 87 in good yields (72-97%). The enantioselectivities were satisfactory (81-90% ee) in the case of imines derived from a,(3-unsaturated aldehydes and moderate (52-77% ee) for aromatic substrates. 

Enantiopure sugar-derived tetrahydroquinolines can be synthesized through a Bi(OTf)3-catalyzed reaction of 8-hydroxy-a, p-unsaturated aldehydes and aryl amines [130] (Fig. 31). 

A -Cyano- and A -(p-toluenesulfonyl)-A -(trimethylsilylmethyl)-5-methylisothio-ureas 269a and 269b have also been utilized as synthetic equivalents of azomethine ylides. ° Reaction of 269a and 269b with aromatic aldehydes and aryl ketones, in the presence of CsF, gives 2-iminooxazolines 270a-e in modest-to-good yield. These 2-iminooxazolines apparently are stable to isolation and do not isomerize to 2-aminooxazolines (Scheme 8.76). 

The reactivity of 9-methylacridine is, as might be expected, similar to that of 4-methyl-pyridine and lepidine, aromatic aldehydes giving either a-aryl-/8 (9-acridyl)ethanols or styrene derivatives depending on the conditions. 

DAMN reacts readily with a-keto aldehydes, a-keto oximes, and x-diketones to give mono- and disubstituted aryl/alkyl dicyanopyrazines (127) in good yield (Scheme 45). 

The classical Hantzsch reaction, the formation of dihydropyridines from an aldehyde, a 5-keto ester and an amine, was first described in 18826. In the 1940s, the interest for this substance class increased due to its pharmacological activity, for example, 4-aryl-1,4-dihydropyrdines form an important class of calcium channel antagonists such as Nifedipin. 

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