Arylation of aldehydes

While the synthesis of fnnctionalised secondary alcohols and amines can be achieved withont catalyst by the addition of organolithium and organomagnesium reagents to C=N and C=0 gronps, these methods lack a significant functional group tolerance. In order to overcome this limitation and access to more functionalised compounds, the catalytic arylation of aldehydes and imines has been extensively studied [2]. 

The facile arylation of aldehydes with arylboronic acid has prompted the exploration of asymmetric versions of this reaction. However, this field has been scarcely explored and only few examples have been reported in the literature, with moderate results. The first diastereoselective example was described by Ftirstner and coworkers. By reacting the Gamer aldehyde 15 with phenylboronic acid under their set of experimental conditions (i.e. RhClj-SH O, IPr HCl) (Scheme 7.4) [21], the secondary alcohol was obtained in higher selectivity than that observed in the addition of phenylmagnesium bromide reported by Joullie (de = 94% versus 66%), with the anti isomer as the major compound [29]. 

Regarding the use of other metals for this transformation, Shirai and co-workers reported that a system constituted by palladium(II) complex [Pd(p-Cl)(r -aUyl)]2 and thioether-imidazolium chloride 19 achieved the arylation of aldehydes with boronic acids [33] and potassium trifluoroborates in good to excellent yields (Scheme 7.5) [34], More recently, Buffard and Itami showed that a NKcod) / IPr-HCl system could catalyse the reaction of arylboronate esters and inactivated aldehydes and ketones (Scheme 7.5) [35]. 

Scheme 3.60 Thiazolidine ligand for arylations of aldehydes with aryl boronic acids.

The transmetallation from (PhBO)3 to diethylzine has been shown to occur in a two-step process (Scheme 9.16). This catalytic system is highly effective for the enantioselective arylation of aldehydes to give diaryl carbinols. ... 

The asymmetric arylation of aldehydes in the presence of a catalytic amount of chiral amino alcohol111 or of chiral tertiary aminonaphthol112 has been described. The reactive arylzinc species have been generated in situ from a boron-zinc exchange instead of employing the more expensive diphenylzinc. The chiral diaryl carbinols have been obtained in high yields and ees. 

Arylation of aldehydes. Aryl group transfer from arylboronic acids to relatively... 

For a-arylation of aldehydes catalytic systems with wide-scoped applicability have been determined. Excellent phosphine ligand for assisting Pd(OAc>2 in the reaction with ArCl is 1, and with ArBr, rac. BINAP or 2. 

The a-arylation of aldehydes is also possible [57,58]. The choice of ligand and solvent is important (Eq. 15) [57]. In the case when a less bulky ligand or a more polar solvent is used, aldol condensation occurs at first, which is follwed by y-arylation to give a 1 2 coupling product. 

McMillan and Allen have accomplished the enantioselective a-arylation of aldehydes using diaryliodonium salts and a combination of copper and organic amine catalysts. This asymmetric protocol has been applied to the rapid synthesis of (5 -ketoprofen, a commercially successful oral and topical analgesic [920],... 

An interesting variation of this reaction is shown in Scheme 2.21 and consists of a Michael reaction between aldehydes and quinones, which results in a procedure for carrying out the formal a-arylation of aldehydes. In this case, the activation of the Michael donor as the corresponding enamine takes place followed by the conjugate addition to the highly electrophilic quinone reagent... 

Efficient catalytic arylation of aldehydes with thioether—imidazohnium carbene hgands 12CPB419. 

MacMillan and co-workers then developed the a-arylation of aldehydes and showed it to be ortfto-selective. The single electron oxidant in this case was [Fe(phen)3] (PFg)3 in place of CAN, as it was shown to provide a superior catalyst/ oxidant combination. The general applicability of this procedure was demonstrated with a wide variety of substrates [33, 34], The mechanism proposed by MacMillan and co-workers is an overall two electron oxidation whereby the 3- Ji-radical cation reacts with the benzene ring to form a bicyclic radical cation 107 that upon further oxidation, generates a dienyl cation 108. Rearomatisation and hydrolysis of the iminium species generates the product and regenerates the catalyst (Scheme 1.27). 

Scheme 1.27 Ortho-selective a-arylation of aldehydes via Organo-SOMO catalysis. ML ...

On the other hand, Jprgensen et al. have reported an interesting a-arylation of aldehydes with electron-rich aromatic compounds such as A-(4-hydroxyphenyl)-4-methylbenzenesulfonamide through a novel anodic oxidation/organocatalytic protocol [95]. As depicted in Scheme 2.29, the reaction firstly involves the... 

Scheme 8.1 Zinc-mediated asymmetric arylation of aldehydes.

Figure 8.3 Examined ligands for the rhodium-catalyzed enantioselective arylation of aldehydes.

Recently, Rondo and Aoyama reported on a nickel/Et-DuPhos-catalyzed arylation of aldehydes using arylboroxines as aryl source (Scheme 8.6) [20]. Although the reactivity of this protocol is satisfying, enantioselectivities were only found to be in the range of 32 to 78%. 

Scheme 8.22 Palladium(ll)-catalyzed conjugate asymmetric arylation of aldehydes 87.

A chelation-assisted mthenium-catalyzed arylation of aldehyde 99 was accomplished in combination with a palladium complex [47]. This cooperative catalysis [48] proved applicable to organostannanes and aryl iodides as arylating reagents (Scheme 9.35). The direct arylation proceeded most likely through ruthenium-catalyzed C—H bond activation, subsequent transmetallation to palladium, and reductive elimination from a palladium intermediate. 

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