Ketones asymmetric arylation

In 2000, Woodward et al. reported that LiGaH4, in combination with the S/ 0-chelate, 2-hydroxy-2 -mercapto-1,1 -binaphthyl (MTBH2), formed an active catalyst for the asymmetric reduction of prochiral ketones with catecholborane as the hydride source (Scheme 10.65). The enantioface differentiation was on the basis of the steric requirements of the ketone substituents. Aryl w-alkyl ketones were reduced in enantioselectivities of 90-93% ee, whereas alkyl methyl ketones e.g. i-Pr, Cy, t-Bu) gave lower enantioselectivities of 60-72% ee. 

Alkylated (R,RHetrahydroindcnyItitanium difluoride and phenylsilane serve to asymmetrically reduce a variety of ketones, especially aryl alkyl ketones, in excellent chemical yields and >96% ee.587 The use of the easier to handle and less expensive PMHS is also highly effective in these transformations. In a related study using the (W, W)-tctrahydroindcny I titanium l,T-binaphth-2,2/-diolate precursor to the active catalyst, similarly impressive results are obtained.588... 

The asymmetric arylation of ketone enolates represents an attractive method for the preparation of optically active carbonyl compounds with a stereogenic quaternary center at the a-position to the carbonyl group. Such types of compounds are important intermediates for natural product synthesis. Replacement of BINAP by 109 provides... 

Buchwald has designed a hindered dialkylphosphino-binaphthyl ligand (3) that is much more active than the original ligand for asymmetric arylation of ketone enolates. Reactions occur at room temperature using only 2 mol % catalyst with enantioselectivities up to 94% [41]. Additionally, the Buchwald group has developed an electron-rich monodentate ligand (4) capable of vinylation of ketone enolates with up to 92% ee [42]. 

Intermolecular a-arylation of the ketone 399 with o-tolyl bromide (398) gives 400 under selected conditions using f-BuONa or KN(SiMe2)2 as suitable bases, and BINAP or DPPF (XLIX) as a bulky ligand [194], Furthermore, asymmetric arylation of the ketone 402 with the bromide 401 gave 403 with 98% ee efficiently by using chiral BINAP [195]. 

Tris[ (l S,2i )-6,6-dimethylbicylo[3.1.1]heptan-2-yl methyl]gallium reacts with ketones above room temperature, and optically active alcohols are obtained as main products (Scheme 145).438 LiGaH4, in combination with an S,0-chelate ligand, 2-hydroxy-2 -mercapto-l,T-binaphthyl (MTBH2), forms an active hydride catalyst for an asymmetric reduction of prochiral ketones with catecholborane. Enantiofacial differentiation is based on the steric requirement of the ketone substituents. Aryl//z-alkyl ketones are reduced in 90-93% ee and branched ketones RC(0)Me (e.g., R = Pr , oC6H11 Bu ) in 60-72% ee (Table 43).439 440... 

PALLADIUM-CATALYSED MULTIPLE AND ASYMMETRIC ARYLATIONS OF VINYL ETHERS CARRYING CO-ORDINATING NITROGEN AUXILIARIES SYNTHESIS OF ARYLATED KETONES AND ALDEHYDES... 

Scheme 14.57 Ni-catalysed asymmetric a-aiylation of ketones with aryl chlorides.

In 2006, Tan and co-workers [88] synthesized a series of chiral imidazolines and found 38 was suitable catalyst for asymmetric BH reactions of vinyl alkyl ketones with aryl aldehydes, which afforded the BH adducts in moderate to high yields and with up to 78% ee in toluene. Recently, Bugarin and Connell [89] applied the Fu s chiral DMAP 39 as catalyst in the MgL-mediated enantioselective BH reaction of cyclopentenone and aldehydes, giving the adducts in good yields and enantioselectivities. 

In addition to molecules containing prochiral sites, racemic molecules can participate in catalytic asymmetric transformations. In some transformations, the stereocenter is destroyed in the course of the reaction, and equilibrating prochiral intermediates are formed. An example of such a process is the asymmetric arylation of ketones (Figure 14.8C). In other cases, one of the enantiomers of the substrate reacts with the asymmetric catalyst significantly faster than the other enantiomer. In this case, an enantioenriched product is formed, and the opposite enantiomer of the reactant remains. This last process is called a kinetic resolution and is illustrated for the conjugate reduction of enones via hydrosilylation (Figure 14.8D). In this case, the top and bottom faces of the C-C double bond are diastereotopic because reaction at each face of the enone generates diastereomeric products. This section of the chapter first presents the principles that relate to reactions at prochiral centers of achiral substrates and then presents the principles that relate to reactions of racemic or meso compounds. 

More recently, the asymmetric hydrosilylation of aryl ketones and aryl imines has been developed using copper catalysts. " In this case, axially chiral biaryl bisphos-phine ligands boimd to copper generate remarkably active catalysts for tihe hydrosilylation of ketones. These reactions occur with high selectivity using the hydrosilane polymer... 

Since the publication by Bolm et al. [3], in 2001, of a review on catalytic asymmetric arylation reactions (Scheme 7.1), many innovative and practical processes have been developed in this area. In this chapter, which concerns the arylation of carbonyl groups (aldehydes, ketones, etc.) and the most important advances that have taken place in the last 10 years or so, enantioselective and nonasymmet-ric arylation of carbonyl groups wHl be discussed, taking into account the different transition-metal catalysts applied. 

Scheme 7.19 Enantioselective rhodium/phosphoramidite-catalyzed asymmetric arylation of trifluoromethyl ketones with arylboronic acids, as described by Minnaard and coworkers [33].

Palladium(0)-catalyzed asymmetric arylation of tert-cyclobutanol 33 with bromobenzene, involving enantioselective C-C bond cleavage, furnished the chiral y-arylated ketone 34 (Scheme 3.13) [24]. Good enantioselectivity was observed when a chiral ferrocenyl P,N-ligand was used. y-Alkenylated and y-allenylated ketones were also obtained by asymmetric ring opening. 

Hamada T, Chieffi A, Ahman J, Buchwald SL. An improved catalyst for the asymmetric arylation of ketone enolates. J. Am Chem. Soc. 2002 124(7) 1261-1268. 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

Chiral diamino carbene complexes of rhodium have been merely used in asymmetric hydrosilylations of prochiral ketones but also in asymmetric addition of aryl boron reagents to enones. 

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