Asymmetric dialkyl zinc addition

The same dendritic ligands were used for the addition of disopropylzinc and diethylzinc to aldehydes (phenyl, 2-naphthyl, / -tolyl) 46). The two ligands were equally selective for the (J )-alcohol product (77% ee 86%, depending on the substrate). Dendrimer 53 was recovered after the reaction between diethylzinc and benzaldehyde and was reused in a consecutive run, giving the same enantioselec-tivity. 

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Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

Scheme 1.22 Kitamura and Noyori s mechanism of the asymmetric addition of dialkyl zinc to aryl aldehydes.

The Cu(I)-catalysed asymmetric conjugate addition of dialkyl zinc reagents to 3-nitrocoumarins 45 gives high yields of 3,4-dihydrocoumarins in a pH-dependent diastereoisomeric ratio. Subsequent decarboxylation gives optically active p-aryl nitroalkanes... 

Building on the success of Woodward s use of an achiral NHC to catalyze the conjugate addition of dialkyl zincs, Alexakis and Roland simultaneously reported the use of chiral NHCs to achieve the asymmetric addition into enones. In Alexakis s system, the catalyst was generated in situ by addition of BuLi to a suspension of imidazolium salt 19, Cu(OTf)2, and enone in toluene followed by addition of Et2Zn (Eq. 28) [63]. While conversions and yields were found to be nearly quantitative, ee values were moderate with 51% being the highest reported. 

Scheme 25 One pot asymmetric addition of dialkyl zinc to a cobalt complexed propargyl aldehyde followed by PKR...

Transformations involving chiral catalysts most efficiently lead to optically active products. The degree of enantioselectivity rather than the efficiency of the catalytic cycle has up to now been in the center of interest. Compared to hydrogenations, catalytic oxidations or C-C bond formations are much more complex processes and still under development. In the case of catalytic additions of dialkyl zinc compounds[l], allylstan-nanes [2], allyl silanes [3], and silyl enolethers [4] to aldehydes, the degree of asymmetric induction is less of a problem than the turnover number and substrate tolerance. Chiral Lewis acids for the enantioselective Mukaiyama reaction have been known for some time [4a - 4c], and recently the binaphthol-titanium complexes 1 [2c - 2e, 2jl and 2 [2b, 2i] have been found to catalyze the addition of allyl stannanes to aldehydes quite efficiently. It has been reported recently that a more active catalyst results upon addition of Me SiSfi-Pr) [2k] or Et2BS( -Pr) [21, 2m] to bi-naphthol-Ti(IV) preparations. 

Notable were highly enantioselective additions of N-phosphonyl imines with dialkyl zinc or hydroxyketones and a one-pot reaction of alkynylzirconocenes with alkynyl phosphazenes and zinc carbenoids to give single isomer cyclopropylphosphonamides. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. Other interesting reports cover the use of phosphoramidates for the synthesis of allylic amines as well as the first example of C-P cleavage of a-aminophosphono acids using periodate. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

For instance, it is reported that a chiral copper catalyst (R,R)-L promotes asymmetric conjugate addition of dialkyl zinc to a,p-unsaturated ketone 19 to form homochiral zinc enolate 20. This intermediate is then trapped in situ with NPP as electrophile, without the need of additional palladium catalysis. Good yield, high trans/cis (95/5) ratio, and excellent enantioselectivity (99%) are obtained. Moreover, the multi-functionalized nature of 21 makes it a versatile intermediate for further elaboration. 

Bos PH, Macia B, Femandez-lbanez MA, Minnaard AJ, Fer-inga BL. Catalytic asymmetric conjugate addition of dialkyl-zinc reagents to a,p-unsaturated sulfones. Org. Biomol. Chem. 2010 8(1) 47 9. 

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