Aromatic electron-rich aldehydes

A study by Hayashi et al. demonstrates that less reactive electron-rich aromatic aldehydes efficiently undergo Mannich reactions under high pressure induced by water freezing [8], For instance, in the Mannich reaction of p-anisaldehyde, 3,4-dimethoxybenzaldehyde or N-acetyl-(4-formyl)aniline, with acetone and p-anisidine, good yields (61-99%) and excellent enantioselectivities (92-97%) have been obtained under water-freezing high-pressure conditions while there is no reaction at room temperature at 0.1 MPa (Scheme 9.6). 

Treatment of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate 171 with KF generates benzyne, which can then react with aromatic aldehydes to furnish 9-aryl-97/-xanthenes in moderate yield (Scheme 55). Electron-rich aromatic aldehydes are necessary to obtain high yields of the desired xanthenes <20040L4049>. 

The precatalyst 17 produced (S)-benzoin (6, Ar = Ph) in very good yield (83%) and enantioselectivity (90% ee). The condensation of numerous other aromatic aldehydes 4 yielded the corresponding a-hydroxy ketones 6 with excellent ee-values of up to 95%. (For experimental details see Chapter 14.20.2). Electron-rich aromatic aldehydes gave consistently higher asymmetric inductions than electron-deficient (i.e., activated) aromatic aldehydes, with lower reaction temperatures or lower amounts of catalyst leading to slightly higher enantioselectivities coupled with lower yields. 

Fig. 14.38. Regioselective Baeyer-Villiger rearrangement of an electron-rich aromatic aldehyde.

Phenyl formates (see Figure 11.34 for synthesis) hydrolyze to phenols more easily than the phenyl acetates shown in Figure 11.32. Overall, these species bring short reaction sequences to an end which may start with any aromatic methyl ketone or with an electron-rich aromatic aldehyde and which end with a phenol with widely variable substituent patterns. 

A convenient and inexpensive method to transform electron rich aromatic aldehydes to phenols," or a,p-unsaturated aldehydes to vinyl formates, utilizes 30% hydrogen peroxide catdyzed by bis(n-nitro-phenyl) diselenide. A two-step formylation/MCPBA oxidation procedure (Scheme 25) was utilized by Kishi and coworkers in the 100 g scale conversion of 2,6-dimethoxytoluene to the mitomycin precursor (76). An organic peroxy acid was not required for the conversion of 9-formyl-6-methylellipticine (77) to... 

The relative reactivity of aldehydes and acetals toward a typical ketene silyl acetal in the presence of TiCU has been revealed by use of competition reactions (Eqs (22) [98, 99], (23) [98], and (24) [98]). Although yields are not necessarily high, perhaps because these experiments were conducted solely to compare the reactivity of the compounds, the results shown in these equations are quite informative (i) acetals are more reactive than the corresponding aldehyde, (ii) aliphatic aldehydes are more reactive than aromatic aldehydes, and (iii) electron-rich aromatic aldehydes are somewhat more reactive than the electron-deficient variety. 

Azaborolyl complex (- -)-218 has been used in a stereoselective Mukaiyama aldol reaction as illustrated in Scheme 32 <2005JA15352>. Complex (- -)-218 reacts with electron rich aromatic aldehydes and silyl ketene acetals to generate adduct 220. X-ray structures indicate the stereochemistry is as illustrated. This stereochemistry is... 

Arylxanthenes are formed when electron-rich aromatic aldehydes react with an excess of arynes. Initial nucleophilic attack by the carbonyl oxygen atom on the aryne generates a benzoxete which isomerises to an o-quinone methide. A [4-i-2]cycloaddition with the aryne completes the sequence <040L4049>. 

Cyanohydrin silyl ethers Yttrium isopropoxide-more likely, the ((-PrO),3Y50 species—complexes with l,3-bis(2-methylferrocenyl)propane-l,3-dione (1) to afford a highly efficient catalyst for the asymmetric silylcyanation of electron-rich aromatic aldehydes with MCjSiCN. 

Also calix[4]arene has been incorporated to the hydroxy moiety of 4-hydroxyproline to give componnd 98 (Fig. 4.13). This system (2 mol%) have been applied as catalyst in the aldol reaction between cyclohexanone with different aromatic aldehydes in water at 25°C. Generally, moderate yields, diastereo- and enantioselectivities were obtained, being highly dependent on the aromatic substitution. Whereas electron rich aromatic aldehydes afforded mainly the syn-aHAoi, the... 

In the same year, Glorius and coworkers successfully introduced dehydroamino ester 47 as the Michael acceptor for the Stetter reaction. Aromatic aldehydes 21 with an electron-withdrawing group worked well. However, electron-rich aromatic aldehydes did not (Scheme 20.23). 

In 2002, Enders and Kallfass [19] synthesized bicyclic triazolium salt 4 that produced benzoin in 83% yield with up to 95% ee. As expected, electron-rich aromatic aldehydes gave significantly better asymmetric results than electron-deficient ones. Lower reaction temperature (0°C instead of room temperature) led to higher enantioselectivities but resulted in lower yields (Scheme 7.4). 

Electron-rich aromatic aldehydes reacted superiorly conqrared with electron-neutral or electron-deflcient counterparts. Six-membered heterocycles such as piperidine, morpholine, andpiper-izine were also feasible substrates. Acyclic amines could also be efficiently cyclized to furnish ring-fused oxazines (75-95% yield). Other oxidants such as FeCH, CAN, DDQ, and I2 gave trace to no conversion, while Ag2N03 was low yielding (only 25% using 2.0 equiv). 

The cobalt complexed cyclopropane diester 4 was then reacted with a variety of aldehydes in the presence of boron trifluoride etherate in dichloromethane to afford the desired tetrahydrofurans 5 in high yields with poor diastereoselective control (Scheme 10.6). The cycloaddition reaction was limited to electron deflcient aromatic, aliphatic, and functionalized aldehydes, where no reaction was observed with electron rich aromatic aldehydes. The tetrahydrofurans were obtained as a 1 1 mixture of cis- and fran -isomers, where the best diastereomeric ratio obtained was 2 1 (5d) in favor of the fran -isomer. Modifying the temperature of the reaction had little effect on the diastereoselectivity. Confirmation of the stereochemistry was achieved by X-ray and NMR analysis of the separated diastereoisomers, including... 

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