Alkyl zinc. enantioselective

The sequential approach is also common in proposals written by synthetic chemists (a multistep synthesis is inherently step by step). Vyvyan (excerpt 13N), for example, proposes a strategy to synthesize a select group of heliannuols (alleo-pathic natural products isolated from the sunflower) in an optically pure form. One approach that he will explore involves enantioselective cross-coupling reactions between an alkyl zinc reagent and an aryl bromide. He begins with experiments that will utilize recently developed catalysts and produce products with known optical rotation data. Subsequent reactions are described that will lead potentially to the desired stereospecific heliannuols A and D. 

Once this process is explored with the model system to assess the level of enantioselectivity, we will then prepare alkyl zinc reagent 48 from 44 using standard methods - - and cross couple 48 to aryl bromide 18 using the appropriate chiral catalysts (Scheme 7). Although the acetonide stereocenter in 48 is somewhat remote from the coupling site, the stereocenter may serve to enhance the stereoselectivity of the cross-coupling process because the two possible products are diastereomers, not simply enantiomers. This reaction will produce 49 from (S)-48 and 30 from (R)-48 that can then be converted to epoxides 31 and 32 using standard methods. Epoxide 31 leads to heliannuol D 4 after base-promoted epoxide cyclization and deprotonation. Similarly, epoxide 32 leads to heliannuol A 1 after acid-promoted cyclization. 

The chiral catalysts 1 to 4 are highly enantioselective in the addition of di(prira-alkyl)zincs to aromatic aldehydes. (IS, 2i )-iV,iV-dibutylnorephedrine [1 (DBNE)] [5] possesses the advantage of its utility as a highly enantioselective catalyst even for the alkylation of aliphatic aldehydes to afford aliphatic sec-alcohols with up to 93% ee [5]. DBNE is also an appropriate chiral catalyst for the addition of diisopropylzinc [di(sec-alkyl)zinc] (98% ee) [15]. (S)-Diphenyl(l-meth-ylpyrrolidin-2-yl)methanol [2 (DPMPM) [6] catalyzes the enantioselective ethylation of aromatic aldehydes to afford almost enantiomerically pure sec-alcohols... 

DAIB =((-)-3-exo-(Dimethylamino)isobomeol) was introduced as a chiral auxiliary (AX) for the enantioselective addition of dialkylzincs to aldehydes [112]. It has been applied for both intermolecular [113a] and intramolecular [113b] formation of ( -aIlyl alcohols from acetylenes and aldehydes via (l-alkenyl)(alkyl)zinc intermediates. 

Lewis acids such as zinc triflate[16] and BF3[17] have been used to effect the reaction of indole with jV-proiected aziridine-2-carboxylate esters. These alkylations by aziridines constitute a potential method for the enantioselective introduction of tryptophan side-chains in a single step. (See Chapter 13 for other methods of synthesis of tryptophans.)... 

While the mechanism of the ammonium salt catalyzed alkylation is unclear, in polar solvents the enantioselectivity of the addition of dialkylzincs to aldehydes generally drops considerably, probably due to uncatalyzed product formation or complexation of the zinc reagent with the polar solvent rather than with the chiral auxiliary. 

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],... 

The zinc alkoxide of 2-methyl-l-(3-quinolyl)propan-l-ol was used in a catalytic amount to give ee up to 94% in the enantioselective alkylation of quinoline-3-carbaldehyde by diisopropyl-... 

The C2-symmetric bifunctional tridentate bis(thiazoline) 222 has been shown to promote the zinc(II)-catalyzed asymmetric Michael addition of nitroalkanes to nitroalkenes in high enantioselectivity <06JA7418>. The corresponding bis(oxazoline) ligand provides comparable enantioselectivity but higher product yield. The same bis(thiazoline) ligand has also been evaluated in the enantioselective Friedel-Crafts alkylation of indoles, but the enantioselectivity is moderate <06OL2115>. 

Both the aldehyde and diethylzinc are activated by the zinc amide, and the ethyl group transformation from diethylzinc to aldehyde furnishes the highly enantioselective alkylation of aromatic aldehydes. 

Nonracemic tra s-2-[aryl(alkyl)thio]cyclohexanols with l/ ,2/ -configuration are prepared with modest to good enantioselectivity in high yield by reaction of 1,2-epoxycyclohexane with various thiols in dichloromethane at 25 °C catalyzed by zinc L-tartrate in a heterogeneous reaction103. 

Table 6.12 Enantioselective catalytic epoxidation of aryl- and alkyl-substituted a,/l-enones using a (i )-BINOL-zinc catalyst (see Figure 6.13).

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