Rhodium-catalyzed conjugate addition

Recently, Krische and co-workers developed an effective protocol for the catalytic desymmetrization and parallel kinetic resolution of enone-diones via tandem conjugate addition-aldol cyclization (Scheme 66).150 This transformation, involving enantioselective rhodium-catalyzed conjugate addition methodology, enabled the formation of two C-G bonds and four contiguous stereogenic centers from simple precursors with high diastereo- and enantiocontrol. 

Scheme 3.1 Rhodium-catalyzed conjugate addition of phenylboronic acid to a,/ -unsaturated ketones [5].

Scheme 3.3 Organoboron compounds used for rhodium-catalyzed conjugate addition [12-15].

Bis(pinacolato)diboron 14 and bis(neopentyl glycolate)diboron 15 have been used for rhodium-catalyzed conjugate addition to a,/ -unsaturated ketones giving /9-boryl ketones, though the asymmetric version has not been reported [15]. 

Scheme 3.4 Catalytic cycle for the rhodium-catalyzed conjugate addition [15].

In 1998, the rhodium-catalyzed conjugate addition of organostannanes to a,/9-unsatu-rated ketones and esters was reported by Oi [29]. In the reaction, which was carried out in the presence of [Rh(COD)(MeCN)2]BF4 in THF at 60°C, a variety of a,/9-unsatu-rated ketones and esters were transformed into the corresponding conjugate addition products. It is noted that the yield was highly dependent on the substitution pattern of the substrates. For example, /9-substituted enone 40 afforded an 86% yield of 41, whereas methyl vinyl ketone 42 gave only an 18% yield of 43 (Scheme 3.14). The addition of water to the reaction mixture improved the reactivity for the formation of 41 (98%) and 43 (80%) [30]. 

Scheme 3.14 Rhodium-catalyzed conjugate addition of phenyltrimethyl-stannane [29, 30],...

Scheme 3.15 Catalytic cycle for rhodium-catalyzed conjugate addition of organostannanes [29],...

The use of organosilanes for rhodium-catalyzed conjugate addition is also feasible. In 2001, Mori reported that the catalytic conjugate addition of aryl(ethyl)silanediols to a,f -unsaturated carbonyl compounds takes place in the presence of [Rh(OH)(COD)]2 in a... 

Scheme 3.16 Rhodium-catalyzed conjugate addition of phenylstannanes [31, 32].

For rhodium-catalyzed conjugate addition using organosilanes, several other conditions have been reported [34]. Cationic rhodium catalysts such as [Rh(COD)2]BF4 and ]Rh(COD)(MeCN)2]BF4 are more active than neutral rhodium catalysts such as ]Rh(OH)(COD)]2. 

Recently, triphenylbismuth has been used for rhodium-catalyzed conjugate addition (Eq. 4) ]36]. The reaction carried out in the presence of [RhCl(COD)]2 or... 

The addition of Rh-Csp a-bonds to enones is a well-studied process. Lee s reaction is predicated on the idea that rhodium-catalyzed conjugate addition of boronic acids to enones can be interrupted by 1,1-insertion into an alkyne. Thanks to the high reactivity of rhodium toward alkynes and the effects of tethering, a partly intramo-... 

Complementary to the use of zinc reagents for the introduction of (functionalized) alkyl groups is the rhodium-catalyzed conjugate addition of aryl- and alkenylboron reagents. This method rapidly became popular, also because arylboron reagents are air and moisture stable and a large variety of them is commercially available . 

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]. 

Both, Hayashi and Carreira developed, independently, chiral dienes as novel ligands in asymmetric catalysis (Figure 8.6) [66]. Early investigations by Miyaura revealed that the rhodium-catalyzed conjugate addition of arylboronic acids to a,P-unsaturated ketones could be very efficiently catalyzed by a rhodium(I) complex of cyclooctadiene [67]. As a consequence, the development of chiral cod-analogues... 

Most of the currently applied protocols for rhodium-catalyzed conjugate addition chemistry involve the use of aqueous solvent systems which ensure catalytic turnover by protonation of the intermediate rhodium enolate. Consequently, tandem reaction sequences with electrophiles other than a proton are troublesome. In early investigations, Hayashi reported a rhodium/BINAP-catalyzed conjugate addition-aldol reaction under anhydrous conditions by use of 9-aryl-9-borabicyclo[3.3.1]no nanes (9-Ar-9-BBN) as aryl sources [117]. The reaction between tert-butyl vinyl ketone (145) with 9-(4-fluorophenyl)-9-BBN (146) and propionaldehyde (147) led to the formation of a syn/anti-mixiuve of 148 in a 0.8 to 1 ratio (Scheme 8.39). 

Scheme 5.17 Rhodium-catalyzed conjugated additions of organotin reagents on unsaturated ketones in...

Maddaford and co-workers have reported the diastereoselective synthesis of C-gly-coside 34m by use of rhodium-catalyzed conjugate addition [27] (Scheme 4.13). The reaction is efficiently catalyzed by cationic rhodium catalysts such as [Rh(cod)2]BF4,... 

In Hayashi s rhodium-catalyzed conjugate addition of boronic acids (Scheme 2.41), (S)-BINAP (139) was used as the chiral ligand to mediate the reaction of cyclohexenone and phenyl-BBN 138. The boron enolate 140 thus formed was clearly identified und fully characterized by spectroscopy and chemical conversions. Taking advantage of the well-known potential of boron enolates for stereoselective aldol additions, the subsequent reaction with propanal led to the aldol adduct 141 that was obtained in dr >99 1 and 98% ee (cf. Section 5.5) [147]. 

Scheme 2.41 Enantioselective rhodium-catalyzed conjugate addition of a borane and subsequent diastereoselective aldol addition of boron enolate 140.

Hayashi and Miyaura pioneered the enantioselective rhodium-catalyzed conjugate addition of arylboronic acids to a variety of Michael acceptors a,P-unsaturated ketones, esters, lactones, amides, and lactams [215]. Generally, water is used as a cosolvent and plays a key role in the catalytic cycle, illustrated in Scheme 5.111 (cycle A) for the conjugate addition of phenylboronic acid to cyclohexenone that, when catalyzed by the Rh(I)-(S)-BINAP complex, leads to 3-phenylcyclohexanone in 97% ee and 93% chemical yield [205a]. The key intermediates of the catalytic cycle, the hydroxorhodium complex 433, the phenylrhodium complex 434, and -bound rhodium enolate 435 were characterized by NMR spectroscopy. The reaction of the hydrorhodium complex 433 with phenylboronic acid leads to a transmetallation to give the phenylrhodium complex 434. Then, the insertion of the carbon-carbon double bond of cyclohexenone into the phenylrhodium bond leads to the formation of the... 

The Meyer-Schuster-type conversion of propargylic alcohols into conjugated enones was found to proceed efficiently in the presence of NHC-Au catalysts. " This process could be coupled with a subsequent asymmetric rhodium-catalyzed conjugate addition, thus expanding the synthetic scope of the transformation. ... 

Frost CG, Penrose SD, Lambshead K, Raithby PR, Warren JE, Gleave R. Rhodium-catalyzed conjugate addition-enan-tioselective protonation the synthesis of a,a -dibenzyl esters. Org. Lett. 2007 9 2119-2122. 

Hayashi investigated the asymmetric, rhodium-catalyzed conjugate addition reaction of organoboronic acids to a variety of unsaturated electrophilic acceptors [46, 144-147). The first successful example of such a transformation involved the use of a Rh-BINAP catalyst (187, Equation 34) [144. As shown for cyclohexenone, the rhodium-catalyzed addition of phenylboronic acid takes place to afford 188 in 96% ee and >99% yield. 

---