Borylation enantioselective

The enantioselective P-borylation of a,P-unsaturated esters with (Bpin) was studied in the presence of various [CuCl(NHC)] or [Cu(MeCN)(NHC)] (NHC = chiral imidazol-2-ylidene or imidazolidin-2-ylidene) complexes. The reaction proceeds by heterolytic cleavage of the B-B bond of the (Bpin), followed by formation of Cu-boryl complexes which insert across the C=C bond of the unsaturated ester. Best yields and ee were observed with complex 144, featuring a non-C2 symmetric NHC ligand (Scheme 2.31) [114]. 

Formal hydration of the double bond appeared by the hydroboration-oxidation sequence. Desymmetrization reactions with catalytic asymmetric hydroboration are not restricted to norbornene or nonfunctionalized substrates and can be successfully applied to meso bicyclic hydrazines. In the case of 157, hydroxy derivative 158 is formed with only moderate enantioselectivity both using Rh or Ir precatalysts. Interestingly, a reversal of enantioselectivity is observed for the catalytic desymmetrization reaction by exchanging these two transition metals. Rh-catalyzed hydroboration involves a metal-H insertion, and a boryl migration is involved when using an Ir precatalyst (Equation 17) <2002JA12098, 2002JOC3522>. 

Use of the boron azaenolate 3, prepared from achiral 2-ethyl-4,4-dimethyloxazoline and the chiral boryl triflate, undergoes aldol condensation to give mainly threo-fi-hydroxy esters with enantioselectivity of about 80% (equation II). 

Only limited success has been reported in the reduction of ketimines due to the low electrophilicity of the imine carbon and the rapid equilibration between the (E)- and (Z)-isomers. However, high enantioselectivity was achieved in catalytic reduction of imines of keto esters (Equation (261))1125 and oximes of acetophenone (Equation (262))1089,1125-1131 cyclic ketones (Equation (263)),1127 and a ketone possessing a boryl group (Equation (264)).1128... 

The use of these boryl complexes in catalytic, enantioselective additions to aldehydes by silyl ketene acetals has also been the subject of intense investigation by Yamamoto (Eq. 30) [108]. Although ethyl and benzyl acetate-derived enol silanes furnished racemic products, the phenyl acetate-derived trimethylsilyl ketene acetals proved optimal, giving adducts in up to 84% ee. Additionally, Yamamoto has documented the use of 184 in aldol addition reactions of propionate- and isobutyrate-derived enol silanes (Eqs. 31 and 32). Thus, the addition of the phenyl acetate derived (E)-enol silane afforded adducts as diastereomeric mixtures with the syn stereoisomer displaying up to 97% ee (Eq. 32). 

For an enantioselective addition of enol silanes to acetals mediated by a boryl complex incorporating a chiral indolyl group, see Kinugasa M, Harada T, Oku A (1996) J Org Chem 61 6772... 

Additional examples of reagent-based enantioselection involve the enantioselective hydrogen atom abstraction by chiral amine-boryl [37] or silanethiyl radicals... 

Enantioselective hydrogen atom abstraction by chiral amine boryl radical 83 allows for kinetic resolution of racemic ester 84. In the specific example illustrated in Eq. (23), the enantioselectivity of the residual enantiomer of the substrate reached 74% (/ ,/ ). It is postulated that a transition state as shown in 86 could account for the asymmetric hydrogen atom abstraction. 

Lam [77] has described highly enantioselective Cu(I)-catalyzed borylative aldol cyclizations of enone diones 237 via a chair-like transition state 238, which resulted in densely functionalized decalin-, hydrindane-, and diquinane-based products 239 containing four contiguous stereocenters, two of which are quaternary (Scheme 11.51). 

Scheme 11.51 Enantioselective Cu(l)-catalyzed borylative aldol cyclization [77]...

The first Cu-catalyzed asymmetric borylative cyclization reaction between cyclohexadienone-containing 1,6-enynes and B2pin2 was established to afford an optically pure d5-hydrobenzo[l ]furan framework bearing alkenylboronate and enone substructures through a tandem process of selective P-borylation of the propargylic ether and subsequent enantioselective conjugate addition to cyclohexadienone (13JA11700). 

The first enantioselective p-boration of activated alkenes was described by Fer-ndndez and coworkers in 2009 using 2mol% of monodentate chiral NHC—Cu complex 100 [90]. p-borylation of a,p-unsaturated esters was achieved with excellent conversion (up to 99%) and moderate enantioselectivities (up to 73% ee) in the presence of 2% of copper complex 100. The substrates with a group at position a were studied as well, but the diastereoselectivities were relatively low (around 60 40) (Scheme 3.61). 

In 2010, McQuade and coworkers described the application of complex 98 in the enantioselective conjugate borylation of acyclic a,p-unsaturated esters (Scheme 3.62) [91]. The copper(I) complex 98 exhibited excellent reactivities (88-95% yields) and enantioselectivities (82-96% ee) for p-borylation of a variety of aliphatic and aromatic a,p-unsaturated esters by using 1 mol% of 98. As typical in NHC-Cu(I)-catalyzed borylation reaction, methanol was a necessary additive in this transformation. The system was highly reactive and catalyst loadings... 

In the same year, another annulated chiral monodentate Af-heterocyclic car-bene 101 based on an isoquinoline was reported by the Hong group (Scheme 3.63). The authors proposed that this isoquinoline-based chiral diami-nocarbene blocks three quadrants of the metal coordination sphere. Its application in enantioselective p-borylation of acyclic a,p-unsaturated amides led to the products in good yields (80-99%) and enantioselectivities (75-87% ee) [92]. Interestingly, changing the double bond geometry from E to Z resulted in reduced yield and enantioselectivity and gave the opposite enantiomer. 

Very recently, Ma and coworkers reported another bicyclic triazolium ligand 102 based on [2.2]paracyclophane and its applications in the asymmetric copper (I)-catalyzed p-borylation of a,p-unsaturated acyclic enones (Scheme 3.64) [93]. The catalyst generated in situ by the reaction of 102 and CU2O was remarkably efficient giving the p-boryl ketones in high yields (up to 99%) and enantioselectivities (up to 97%). A screening of the ligand revealed that the absolute... 

Scheme 3.9 Aggarwal s enantioselective litbiation-borylation. (Adapted witb permission from ref. 60 2010 Wiley-VCH Verlag GmbH.)...

The ready availability of arylboronates by an aromatic C-H borylation provides a synthetic link to the well-established palladium-catalyzed cross-coupling reactions, rhodium-catalyzed 1,4-addition to a,p-unsaturated carbonyl compounds, and other bond forming reactions using arylboronic esters (Scheme 2.12). Borylation of 1,3-dichlorobenzene with pinacolborane is followed directly by a cross-coupling reaction with methyl p-bromobenzoate for the synthesis of a biaryl product in 91% yield [60]. Pinacol esters of arylboronic acids react much slower than the free acids [62], but both derivatives achieve high isolated yields and comparable enantioselectivities (91% ee) in asymmetric 1,4-addition to N-benzyl crotonamides [63]. Borylation of arenes followed by oxidation of the C-B bond is synthetically equivalent to an aromatic C-H oxidation to phenols [64]. Oxidation of the resulting arylboronates with Oxone in a 1 1 acetone-water solution is completed within 10 min at room temperature. 

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