Boron, chiral catalysts

Some of the developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds have origin in Diels-Alder chemistry, where many of the catalysts have been applied. This is valid for catalysts which enable monodentate coordination of the carbonyl functionality, such as the chiral aluminum and boron complexes. New chiral catalysts for cycloaddition reactions of carbonyl compounds have, however, also been developed. 

The possibility of using chiral auxiliaries or chiral catalysts to achieve enantio-selective Claisen rearrangements has been explored.253 One approach is to use chiral boron enolates. For example, enolates prepared with the chiral diazaborolidine bromide O lead to rearranged products of more than 95% enantiomeric excess.254... 

The directive effect of allylic hydroxy groups can be used in conjunction with chiral catalysts to achieve enantioselective cyclopropanation. The chiral ligand used is a boronate ester derived from the (VjA jA N -tetramethyl amide of tartaric acid.186 Similar results are obtained using the potassium alkoxide, again indicating the Lewis base character of the directive effect. 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

Perhaps the most attractive method of introducing enantioselectivity into the Diels-Alder reaction is to use a chiral catalyst in the form of a Lewis acidic metal complex. In recent years, this area has shown the greatest progress, with the introduction of many excellent catalytic processes. Quite a number of ligand-metal combinations have been evaluated for their potential as chiral catalysts in Diels-Alder reactions. The most commonly used metals are boron, titanium, and aluminum. Copper, magnesium, and lanthanides have also been used in asymmetric catalytic Diels-Alder reactions. 

The directive effect of allylic hydroxyl groups can be used in conjunction with chiral catalysts to achieve enantioselective cyclopropanation. The chiral ligand used is a boronate... 

High enantioselectivities (up to 94%) are obtained in the sodium borohydride reduction of aliphatic ketones using a tartaric acid-derived boronic ester (TarB-N02) as a chiral catalyst. A mechanism (Scheme 14) involving an acyloxyborohydride intermediate has been postulated.319... 

Asymmetric hydroboration of prochiral alkenes has been achieved using transition metal catalysts and chiral phosphines as ligands to obtain enantiomerically pure alkyl boronates <1997CC173>. Catalysts such as Rh(COD)2+BF4 , Rh(COD)2+Cl, Rh+BF4 , etc., in combination with chiral phosphines like DIOP 71, BINAP 72, CHIRAPHOS 73, DIPAMP 74, BDPP 75, ferrocene-based diphosphines 76<1999TL4977>, etc., have been employed for the asymmetric hydroboration of prochiral alkenes with moderate to high ee (DIOP = 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane BINAP = 2,2-bis(diphenyl-phos-phanyl)-l,1-binaphthyl CHIRAPHOS = 2,3-bis(diphenylphosphino)butane DIPAMP = l,2-bis[(2-methoxyphe-nyl)phenylphosphino]ethane BDPP = 2,4-bis(diphenylphosphino)pentane). 

The palladium-catalyzed silylboration of typical allenes exhibited a strong tendency to occur at the internal double bond giving allylsilanes, which undergo allylation of aldehydes in the presence of a Lewis acid (Equation (44)).254 257 The selectivity can be varied by changing the substituents, but the boron atom always added to the central carbon. Enantioselective silylboration of terminal monosubstituted allenes was demonstrated by double asymmetric induction using chiral silylboranes and chiral catalysts (Equation (45)). 

Without question, the most important developments in this field over the past 10 years have been in the area of enantioselective hydroborations. New chiral catalyst systems are typically tested in hydroborations of vinyl arenes, as reactions using HBcat and a cationic rhodium catalyst are well known to give selective formation of the unusual branched isomer. In related studies, enantiopure 2,2-disubstituted cyclopropyl boronates were easily prepared via the catalytic asymmetric hydroboration of 3,3-disubstituted cyclopropenes using a number of chiral neutral rhodium complexes (equation 13). Directing groups, such as esters and alkoxymethyl substituents, were necessary for achieving... 

Catalytic Asymmetric Diels-Alder Reaction. Amino alcohol (1) combined with Boron Tribromide generates a chiral catalyst for the asymmetric Diels-Alder reaction (97% ee) of unsaturated aldehydes and dienes. ... 

Helmchen and co-workers [13] independently achieved similar results with catalysts of CAB 3 derived from valine (R = /-Pr). When R is 2,4,6-trimethylphenyl, the cycloaddition of crotonaldehyde and cyclopentadiene occurs with 72 % ee exo endo = 3 97) in the presence of 0.2 equiv. chiral catalyst. More recently, the same authors systematically investigated the influence of different experimental conditions on the enantioselectivity [15]. Improved enantioselectivity was obtained in THE or by addition of THE (ee up to 86 %). A transition-state model is proposed for prediction of the absolute configuration of the adducts (Eig. 2). In this model, the R group directs the R S02 group to the opposite side of the ring, where the latter group again participates in trans attack on boron. The conformation of the complexed enal has been determined to be s-cis, as has the coordination of carbonyl to boron syn to H. This model correctly predicts the outcome of all the examples studied. 

Mukaiyama and co-workers have reported that prolinol derivatives combined with BBrs produce promising catalysts for some Diels-Alder reactions [26]. Methacrolein and cyclopentadiene, for example, afford the exo adduct (exoiendo > 99 1) in 97 % ee (reaction at -78 °C in dichloromethane with 20 mol % catalyst). The chiral catalyst is believed to be the HBr adduct salt of the amino boron derivative (Eq. 26). 

The efficiency of haloboranes as Lewis add catalysts and the sensitivity of the boron atom environment to steric hindrance (see Chapter 6) make boron compounds useful chiral catalysts. Hawkins and Loren [779] prepared enantiopure chloroborane (17 ,2I )-3.6, and they showed that the complex 3.6 with methyl crotonate lies under the s-trans conformation 9.40 both in the solid state and in solution. This conformation is also the reactive one, and [4+2]-cycloadditions of acrylates with cyclopentadiene or cydohexadiene catalyzed by (17 ,2i )-3.6 lead highly selectively to the product resulting from the attack of the diene on the unshielded face of complex 9.40 (Figure 9.15). 

The product is obtained in 95% yield and 94% ee. In the counterpart in solution, the ee was only 21-50%. Polymeric chiral catalysts have also been used in the addition of zinc alkyls to aldehydes. Use of a proline-based copolymer in a continuous asymmetrical synthesis with an ultra filtration membrane gave 80% ee (10.61).138 There was no deactivation in 7 days. A boron-containing polymer (10.62) gave only 28-51% ee compared with the 65-75% ee found with model compounds in solution.139... 

The first examples of the enantioselective Simmons-Smith cyclopropanations mediated by a chiral catalyst are very recent. Scheme 6.33 shows three catalysts for the cyclopropanation of rrans-cinnamyl alcohol. The most selective appears to be Charette s dioxaborolane (Scheme 6.33c, [120-122], which also affords the highest yield of product, although this procedure is only suitable for small scale.With other olefins, such as cis and trans disubstituted alkenes and P,P-trisubstituted alkenes, the yields are nearly as good and the enantioselectivities are 96-97%. An important finding in this study [120] was that, in addition to the Lewis acid (boron) that binds the alcohol, a second atom to chelate the zinc is also necessary. In the... 

This reduction method has a number of advantages that include wide scope, predictable absolute stereochemistry, ready availability of the chiral catalyst in both enantiomeric forms, high yields, experimental ease, recovery of the catalyst (as the amino alcohol), and low cost of goods. The most common form of the chiral oxazaborolidine is derived from prolinol and has a methyl substituent on the boron atom (B-Me-CBS) 1. When one conducts a reduction on a novel system for the first time, this catalyst provides a good compromise of cost, enantioselectivity, and experimental ease. If sufficient control is not observed with this reagent, one can then systematically evaluate the numerous variations of this framework. 

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