BINAP addition reactions

In 1997, Miyaura and co-workers reported the nonasymmetric version of 1,4-addition of aryl- and alkenylboronic acids to a,/ -unsaturated ketones using rhodium-phosphine complex as the catalyst.97 Later, Hayashi and Miyaura realized the asymmetric 1,4-addition with high catalytic activity and enantioselectivity.98 In the presence of ( y)-BINAP, the reaction of 2-cyclohexenone with 2.5 equiv. of phenylboronic acid gave (A)-3-phenylcyclohexanone with 97% ee (BINAP = 2,2 -bis (diphenylphosphino)-l,l -binaphthyl Scheme 29).99... 

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... 

Rhodium-catalyzed asymmetric 1,4-addition reactions have been applied to various other a,p-unsaturated compounds as well. Thus, Rh/(5)-binap can catalyze the asymmetric 1,4-addition of arylboroxines to ot,p-unsaturated phosphonates in high yield and ee (Figure 3.37). The key to the success in achieving high yield is the... 

Fumaric and maleic compounds are also suitable substrates in the rhodium-catalyzed asymmetric 1,4-addition reactions. While phosphorus-based chiral ligands, such as (/f)-binap, provide low enantioselectivity for these substrates (<51% ee), chiral diene ligands 38 and 45 are particularly effective for achieving high ee (Figures 3.39 and 3.40). 

As another way of constructing nitrogen-containing heterocycles enantioselec-tively, the use of 3-aIkoxycarbonyl-3-pyrrolines as substrates has also been described in the rhodium-catalyzed asymmetric 1,4-addition reactions (Figure 3.41). Among the conditions examined, it was found that [Rh(OH)(cod)]2/(5)-binap catalyst is uniquely effective for achieving high yield of the 1,4-adducts. 

Shibasaki has examined catalysis of a complex, prepared in situ from PdCl2, AgOTf, (R)-or (S)-BINAP, 4 A molecular sieves, and H20, in the aldol addition reaction of enolsilanes by (Eq. 8B2.5) [13]. Under these conditions, aryl methyl ketone-derived trimethylsilyl enolates add to benzaldehyde and hydrocinnamaldehyde, affording adducts with up to 73% ee. 

Yamamoto has recently described a novel catalytic, asymmetric aldol addition reaction of enol stannanes 19 and 21 with aldehydes (Eqs. 8B2.6 and 8B2.7) [14]. The stannyl ketones are prepared solvent-free by treatment of the corresponding enol acetates with tributyltin methoxide. Although, in general, these enolates are known to exist as mixtures of C- and 0-bound tautomers, it is reported that the mixture may be utilized in the catalytic process. The complexes Yamamoto utilized in this unprecedented process are noteworthy in their novelty as catalysts for catalytic C-C bond-forming reactions. The active complex is generated upon treatment of Ag(OTf) with (R)-BINAP in THF. Under optimal conditions, 10 mol % catalyst 20 effects the addition of enol stannanes with benzaldehyde, hydrocinnamaldehyde, or cinnamaldehyde to give the adducts of acetone, rerf-butyl methyl ketone (pinacolone), and acetophenone in good yields and 41-95% ee (Table 8B2.3). 

Jorgensen et al. reported that C2-symmetric bis(oxazoline)-copper(II) complex 25 also acts as chiral Lewis acid catalyst for a reaction of allylic stannane with ethyl glyoxylate [37]. Meanwhile, p-Tol-BINAP-CuCl complex 26 was shown to be a promising chiral catalyst for a catalytic enantioselective allylation of ketones with allyltrimethoxysilane under the influence of the TBAT catalyst [38]. Evans and coworkers have developed (S,S)-Ph-pybox-Sc(OTf)3 complex 27 as a new chiral Lewis acid catalyst and shown that this scandium catalyst promotes enantioselective addition reactions of allenyltrimethylsilanes to ethyl glyoxylate [39]. But, when the silicon substituents become bulkier, nonracemic dihydrofurans are predominantly obtained as products of [3+2] cycloaddition. 

The tributyltin enolates 74 are readily prepared from the corresponding enol acetates and tributyltin methoxide in the absence of solvent [34]. The tin enolates thus obtained occur in the 0-Sn form and/or the C-Sn form, and both species can be used for the aldol reaction of this system. Although the tin enolates themselves have adequate reactivity toward aldehydes [34c], in the presence of the BINAP silver(I) catalyst the reaction proceeds much faster even at -20 °C. Optimum conditions entail the use of THF as solvent and the results employing these conditions in the catalytic enan-tioselective aldol reaction of a variety of tributyltin enolates with typical aromatic, a,/3-unsaturated, and aliphatic aldehydes are summarized in Table 2. TTie characteristic features are (i) All reactions proceed to furnish the corresponding aldol adducts 75 in moderate to high yield in the presence of 10 mol % (i )-BINAP AgOTf complex at -20 °C for 8 h, and no dehydrated aldol adduct is observed (ii) with an a,j3-unsaturated aldehyde, the 1,2-addition reaction takes place exclusively (entry 3) (iii) a bulky alkyl substituent of tin enolate increases the enantioselectivity of the aldol reaction. For instance, the highest ee (95 % ee) is obtained when the tin enolate prepared from pinacolone 77 or rert-butyl ethyl ketone 79 is added to aldehydes (entries 2, 7, and 8) (iv) addition of the cyclohexanone-derived enol tributylstannane 78 (( )-... 

Cu(I). Carreira and co-workers have documented a class of Cu-mediated dieno-late aldol addition reactions that are postulated to proceed through an intermediate metalloenolate (Eq. (8.26)) [40]. The active catalyst is generated upon dissolution of p-tolbinap and Cu(OTf)2 in THE followed by addition of Bu4NPh3Sip2 as an anhydrous fluoride source. The putative Cu-fluoride complex initiates the formation of a Cu-dienolate that subsequently participates in a catalytic, enantioselec-tive addition reaction. Using as little as 0.5 mol% catalyst, the protected acetoace-tate adducts are isolated in up to 94% ee [41]. The use of the corresponding p-tol-binap-Cu(OrBu) complex prepared in situ from Cu(OfBu) and binap functions as a competent catalyst. This feature is consistent with an intermediate metal alkox-ide in the catalytic cycle, namely, the first-formed metal aldolate adduct. The... 

The prominent asymmetric Michael-type addition reaction of arylborane was realized using binap-Rh catalyst 38 (Eq. (12.32)) [77, 78],... 

Addition reactions. By intramolecular hydroacylation in an ionic liquid, indanones are prepared in a Rh-catalyzed reaction, the metal ion in use is ligated to (R)-BINAP. ... 

For all reactions studied, the activity of the supported catalysts was higher than for the similar biphasic ionic liquid system, which was ascribed to improved mass transfer between the substrates and the ionic liquid phase. In addition, the observed product selectivities of 64-87% and enantioselectivity of 97% for the SILP-Ru-(S)-BINAP catalyzed reaction equalled those of the homogeneous reference reactions. No indication of rhodium metal leeching was found by AAS analysis of the reaction filtrate. 

The rhodium-catalyzed addition of aryl- and 1-alkenylboronic acids tooc, unsaiurated ketones, aldehydes, esters, and amides gave the conjugate 1,4-addition products in high yidds. The ifaodium(I) complexes also catalyzed the 1,2-addition of organoboronic acids to aldehydes or N-sulfonyl aldimines. The dficiency of protocol was demonstrated in the asymmetric addition reactions of organoboronic acids in the presoice of a rhodium(acacV BINAP complex. 

Phosphine-AgOTf complexes are known to promote Michael addition reactions. Kobayashi and Shirakawa have achieved asymmetric Michael addition of P-ketoester to nitroalkenes catalyzed by (R)-Tol-BINAP-AgOTf in water [68]. When cyclopentanone-2-carboxylic acid tert-butyl ester (50) and trans- -nitrostyrene (51) were used as substrates, the Michael adduct (52) was obtained in 71% yield with 77 23 diastereomeric ratio. The major diastereomer showed 78% ee (Scheme 18.19). 

While testing two different catalysts, Tanaka found that cationic rhodium in a binary system (cationic Rh(I)/H8-binap) is effective in chemo- and regioselective addition reactions of terminal alkynes with acetylenedicarboxylate to form 1,2,3,4-tetra-substituted benzenes with excellent yield of 99% [9, 44, 45]. It is also important to note that this reaction is tolerant to a large number of functional groups, including alkenes, alkyl halides, and esters. Although cationic iridium complex Ir(I) did not give a positive result in the cycloaddition reactions, the authors showed that the catalytic system with neutral Ir(I) can facilitate cycloaromatization of dimethyl acetylenedicarboxylate and terminal alkynes [45]. 

Catalysis with BINAP-CuFz, Carreira and co-workers have recently reported a novel aldol addition reaction using a putative Cu(I) fluoride complex as catalyst [32]. The cmiqilex is readily assembled in situ upon dissolving BINAP and CufOTflj, in THF followed by addition of Bu4NPh3SiF2, as an anhydrous fluoride source. Dienolate 105 undergoes addition to a wide range of aldehyde substrates at -78°C with 5 mol % catalyst, giving the protected acetoacetate adducts with up to 94% ee. The reaction has been mechanistically examined in some detail, leading to the postulation that the addition process includes a metalloenolate in the catalytic cycle as relevant reactive intermediate (Scheme 8B2.11) [33]. This perspective contrasts the more traditional role of transition-metal catalysis of the Mukaiyama aldol addition reaction wherein the metal functions as a Lewis acid and activates the electrophilic aldehyde partner. 

RECENT ADVANCES IN ASYMMETRIC ALDOL ADDITION REACTIONS (S)-ToI-BINAP CuF2 + 105... 

Addition reactions of dienolates and aldehydes can also be effected through the use of bisphosphine copper(I) complexes [145, 146]. A mixture of p-Tol-BINAP, Cu(0Tf)2, and (Bu4N)Ph3Sip2 leads to a complex that efficiently promotes rapid aldol addition reactions of acetoacetate-derived dienolates to give adducts with high yields and selectivities. The addition to crotonaldehyde served as an important launch point in Carreira s total syn-... 

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. 

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