Rhodium-catalyzed addition of arylboronic

Murakami [27] and Lautens [28] independently reported the rhodium-catalyzed addition of arylboronic acids to oxanorbornenes (Scheme 3.12). Murakami reported that the reaction of oxabenzonorbornadiene 37 a with phenylboronic acid 2m, in the presence of a rhodium-P(OEt)3 catalyst in MeOH at reflux, gave an 86% yield of the ring-opened alcohol 38 am. Lautens reported the asymmetric version of the reaction, where high enantioselectivity was observed with chiral ferrocenylbisphosphine hgand 39 in a... 

Alternatively, it is also possible to use in situ generated N Boc imines as electro philes [117]. When a carbamoyl sulfones are treated under the rhodium catalyzed addition of arylboronic acids, the imine is formed in situ, and the nucleophilic addition proceeds smoothly to generate the N Boc protected amine (Scheme 1.34). 

The rhodium-catalyzed addition of arylboronic acids to a, 3-unsaturated ketones was first reported by Miyaura in 1997 [44], and only a short time thereafter the first enantioselective addition was documented by Hayashi [45]. Excellent reviews are available that summarize the early developments in this rapidly expanding field of asymmetric catalysis [46] consequently, only recent advances wiU be included in this section. 

In 2005, Bolm and coworkers disclosed a new planar-chiral imidazolium salt 30 incorporating a chiral Al-substituent (Scheme 3.16) [35]. Its apphcation in rhodium-catalyzed additions of arylboronic acids to aromatic aldehydes was demonstrated, and the corresponding diarylmethanols were obtained with up to 38% ee. Since the hgand bears two chiral elements, match and mismatch effects were observed by showing that NHC 31, which is the diastereomer of 30, did not give any enantioinduction. 

Scheme 7.3 Rhodium-catalyzed addition of arylboronic acids to aldehydes, as described by Furstner and Krause [5].

Lautens et al. reported the rhodium-catalyzed addition of arylboronic acids to vinyl-substituted nitrogen heteroaromatic compounds [32]. The reaction of 2-vinylpyridine (42a) with phenylboronic acid (2m) and [RhCl(cod)]2/TPPDS catalyst in the presence of sodium carbonate and sodium dodecyl sulfate (SDS) as a phase-transfer agent in water at 80 °C for 15 h gave a 84% yield of the addition product 43am (Scheme 4.17). The water-soluble TPPDS was a ligand of choice to help dissolve the catalyst in water. Under these conditions, the addition of arylboronic acids was also observed for sev-... 

Scheme4.31 Rhodium-catalyzed addition of arylboronic adds to alkynyl nitrogen heteroaromatic compounds.

Miyaura also [50] reported rhodium-catalyzed additions of arylboronic acids to aldimines. Despite the potential production of water from boronic adds by cydic trimerization, no hydrolysis of N-sulfonyl aldimines was observed when boronic acids were used in the rhodium-catalyzed addition to aldimines in anhydrous diox-ane. The reactions proceeded well, regardless of the presence of both an electron-withdrawing and an electron-donating group on the aldehyde or the arylboronic add. For example, the reaction of N-sulfonyl aldimine 79a with boronic acid 2o catalyzed by cationic rhodium [Rh(cod) MeCN)2]BF4 gave 87% yield of the product 80ao, and... 

Imines derived from N tert butanesulfinamide also undergo diastereoselective rhodium(I) catalyzed addition of arylboronic acids [61] (Scheme 1.16), a reaction that has been primarily developed for catalytic asymmetric processes (see below). 

The catalytic asymmetric synthesis of diarylmethylamines by a rhodium/phos phoramidite catalyzed addition of arylboronic adds to N,N dimethylsulfamoyl pro tected aldimines has been reported by de Vries and Feringa [118], The reaction produces very high yields and high enantioselectivities of the protected amine. Deprotection of the amine is achieved without any racemization upon heating the product in the microwave with 1,3 diaminopropane (Scheme 1.35). 

A diastereoselective approach to these chiral building blocks was developed by Ellman (Scheme 8.15) [40]. Thus, N-tert-butylsulfinyl aldimines 57 were employed as electrophiles in the rhodium/phosphine 58-catalyzed addition of arylboronic acids. Whereas Ellman s procedure requires heating, Batey discovered that an amine base allows the reaction to take place at ambient temperature [41]. However, it is worth noting that Ellman s process can also be carried out in an enantioselec-tive way by using N-diphenylphosphinoyl aldimines 48 as substrate and Degu-PHOS (56) as ligand (87-97% yield, 88-94% ee) (Scheme 8.14 Figure 8.4). 

Scheme 5.8 Rhodium(l)/(fl)-3,5-diCF3-SYNPFIOS-catalyzed addition of arylboronic acids to several maleimides [27].

Arylation of alkynes via addition of arylboronic acids to alkynes represents an attractive strategy in organic synthesis. The first addition of arylboronic acids to alkynes in aqueous media catalyzed by rhodium was reported by Hayashi et al.89 They found that rhodium catalysts associated with chelating bisphosphine ligands, such as 1,4-Ws(diphenyl-phosphino)butane (dppb) and 1,1 -/ E(diphenylphospliino)fcrroccnc... 

In addition to aryl halides and triflates, organometallic reagents can be utilized for the catalytic arylation reaction. The rhodium-catalyzed arylation of arylpyridines proceeds with the use of tetraarylstannanes (Equation (67)).83 The ruthenium-catalyzed reaction of aromatic ketones with arylboronates affords the ortho-arylated aromatic ketones (Equation (68)).84... 

Rhodium(i) complexes are excellent catalysts for the 1,4-addition of aryl- or 1-alkenylboron, -silicon, and -tin compounds to a,/3-unsaturated carbonyl compounds. In contrast, there are few reports on the palladium(n) complex-catalyzed 1,4-addition to enones126,126a for the easy formation of C-bound enolate, which will result in /3-hydride elimination product of Heck reaction. Previously, Cacchi et al. described the palladium(n)-catalyzed Michael addition of ArHgCl or SnAr4 to enones in acidic water.127 Recently, Miyaura and co-workers reported the 1,4-addition of arylboronic acids and boroxines to a,/3-unsaturated carbonyl compounds. A cationic palladium(n) complex [Pd(dppe)(PhCN)2](SbF6)2 was found to be an excellent catalyst for this reaction (dppe = l,2-bis(diphenyl-phosphine)ethane Scheme 42).128... 

Following the initial work by Hayashi and Miyaura using (5)-binap, several other chiral ligands were reported to achieve high enantioselectivity in the rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to ot,p-enones (Figure 3.18). A polymer-supported (X)-binap analog 42 was also synthesized and it was successfully utilized in the rhodium-catalyzed asymmetric 1,4-addition reactions in water (Figure 3.19)." The stereoselectivities observed in this system are comparable to those obtained in the unsupported Rh/(5)-binap system. It was also... 

Figure 3.18. Chiral ligands that exhibit high enantioselectivity in the rhodium-catalyzed 1,4-addition of arylboronic acids to a,P-enones.

An asymmetric 1,4-addition of arylboronic acids to coumarins such as 220 catalyzed by rhodium has been achieved in greater than 99% ee (Equation 21) <2005OL2285>. This method should prove useful for the synthesis of enantiomerically enriched compounds that contain a stereogenic center between two aryl groups. This methodology was used in the total synthesis of (R)-tolterodine. 

These monodentate ligands, containing very bulky chiral N-substituents, have been applied in the asymmetric rhodium(I)-catalyzed conjugate addition of arylboronic acids to a-enones (Scheme 38) originally developed by Miyaura, Hayashi and coworkers [98]. 

Arylboronic acids added to alkynes975-977 and activated alkenes such as norbornene978-981 or 2-vinylpyridines982 in the presence of a rhodium(i) catalyst. Addition of arylboronic acids to allenes was reported to be catalyzed by Pd(PPh3)4 in the presence of AcOH.983... 

Catalytic, Enantioselective Addition of Arylboronic Acids to Cycloalkenones. A complex between ligand 1 and a rhodium(I) salt was found to catalyze the asymmetric 1,4-addition reaction of arylboronic acids to cyclohexenone and cyclohep-tenone. The reaction proceeds with high enantiocontrol and excellent yields (eq 4). Lower enantiomeric excesses were observed with cyclopentenone (83% ee), but a variety of substituted phenyl-boronic acids could be used. 

Additionally, the efficient synthesis of substituted phenylalanine-type amino acids using a rhodium catalyzed, conjugate addition of arylboronic acids has been described. The reactions are run in water using a low loading (0.5 mol%) of the rhodium catalyst [28]. 

Since 2004, considerable progress has been achieved in the rhodium-catalyzed enantioselective addition of arylboronic acids or arylboroxines to various classes of aryl imines 42 (Scheme 8.14). 

The rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to a, 3-unsaturated carbonyl compounds is one of the most versatile and robust methods for the stereoselective introduction of aryl groups (Scheme 8.17). In contrast, copper-catalyzed processes generally transfer alkyl groups with high selectivities, but perform only poorly in aryl transfer [43]. 

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