Chiral 1,3-diol catalyst

The hydride-donor class of reductants has not yet been successfully paired with enantioselective catalysts. However, a number of chiral reagents that are used in stoichiometric quantity can effect enantioselective reduction of acetophenone and other prochiral ketones. One class of reagents consists of derivatives of LiAlH4 in which some of die hydrides have been replaced by chiral ligands. Section C of Scheme 2.13 shows some examples where chiral diols or amino alcohols have been introduced. Another type of reagent represented in Scheme 2.13 is chiral trialkylborohydrides. Chiral boranes are quite readily available (see Section 4.9 in Part B) and easily converted to borohydrides. 

Choudary, B.M., Chowdari, N.S., Mahdi, S., Kantam, M.L. (2003) A Trifimctional Catalyst for One-Pot Synthesis of Chiral Diols via Heck Coupling-N-Oxidation-Asymmetric Dihydroxyla-tion Application for the Synthesis of Diltiazem and Taxol Side Chain. Journal of Organic Chemistry, 6S, 1736-1746. 

A chiral zirconium catalyst generated from Zr(0,-Bu)4 and (R)-3,3 -diiodo-1,1 -binaphthalene-2,2 -diol [(f )-3,3/-l2BINOL] catalyzed... 

Catalytic enantioselective synthesis of vzc-diols is a challenging issue. Chiral induction using chiral ligands is difficult to achieve. The moderately enantioselective pinacolization of benzaldehyde is demonstrated to be performed by the chiral titanocene catalysts 15 and 16 [42,43]. 

Thirteen different chiral diol ligands were used (Scheme 25), leading to a catalyst library of 104 members.121 In a model reaction benzaldehyde (51), (R = Ph) was used as the carbonyl component, HPLC being used to ascertain the enantiopurity of (92). Initially 1 mol.% of catalyst was used. In the primary screening catalysts modified by L4, L5, L6, and L7 turned out to be excellent (77-96% ee yields 63-100%). Thereafter the catalyst loading of Lm/Ti/Lra (m, n = A-l) was decreased to 0.1 mol.%, but this led to only trace amounts of product. Finally, the solvent was... 

Hydride reductions of C = N groups are well known in organic chemistry. It was therefore obvious to try to use chiral auxiliaries in order to render the reducing agent enantioselective [88]. The chiral catalyst is prepared by addition of a chiral diol or amino alcohol, and the active species is formed by reaction of OH or NH groups of the chiral auxiliary with the metal hydride. A major drawback of most hydride reduction methods is the fact that stoichiometric or higher amounts of chiral material are needed and that the hydrolyzed borates and aluminates must be disposed of, which leads to increased costs for the reduction step. 

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... 

The self-assembly of a chiral Ti catalyst can be achieved by using the achiral precursor Ti(OPr )4 and two different chiral diol components, (R)-BINOL and (R,R)-TADDOL, in a molar ratio of 1 1 1. The components of less basic (R)-BINOL and the relatively more basic (R,R)-TADDOL assemble with Ti(OPr )4 in a molar ratio of 1 1 1, yielding chiral titanium catalyst 118 in the reaction system. In the asymmetric catalysis of the carbonyl-ene reaction, 118 is not only the most enantioselective catalyst but also the most stable and the exclusively formed species in the reaction system. 

To a much smaller extent non-enzymic processes have also been used to catalyse the stereoselective acylation of alcohols. For example, a simple tripeptide has been used, in conjunction with acetic anhydride, to convert rram-2-acctylaminocyclohexanol into the (K),(R)-Qster and recovered (S),(S)-alcohol[17]. In another, related, example a chiral amine, in the presence of molecular sieve and the appropriate acylating agent, has been used as a catalyst in the conversion of cyclohexane-1(S), 2(/ )-diol into 2(S)-benzoyloxy-cyclohexan-1 f / j-ol1 IS]. Such alternative methods have not been extensively explored, though reports by Fu, Miller, Vedejs and co-workers on enantioselective esterifications, for example of 1-phenylethanol and other substrates using /. vo-propyl anhydride and a chiral phosphine catalyst will undoubtedly attract more attention to this area1191. 

Chiral titanium catalyst for asymmetric Diels-Alder reactions. A Japanese group2 recently reported that a chiral titanium reagent (1), prepared in situ from TiCl2(0-f-Pr)2 and the chiral diol 2, derived from L-tartaric acid, in combination... 

Kagan and coworkers studied the reaction between cyclopentadiene and 310 in the presence of aluminum alcoholates of chiral diols and their chiral mono ethers208. Among the various diols studied, only 1,1-diphenyl-1,2-propanediol (325) gave satisfactory results. Optimization by variation of the dienophile/catalyst ratio, aging of the catalyst and variation of the temperature ultimately resulted in a maximum of 86% ee at —100 °C. 

Reilly and Oh explored the asymmetric induction of chiral catalysts derived from bis(dichloroborane) 397 in the cycloaddition of cyclopentadiene with a-bromoacrolein and methacrolein. /V-Tosyltryplophan (394) and chiral diols 395 and 396 were employed as chiral ligands246,247. The application of chiral iV-tosyltryptophan afforded the best results (equation 118, Table 22). 

Chiral titanium catalysts have generally been derived from chiral diols. Narasaka and colleagues251 developed an efficient catalyst, 406, prepared from TiCl2(OPr- )2 and a (+)-tartaric acid derived 1,4-diol. These authors found that Af-crotonyl-l,3-oxazolidin-2-one (404) reacted with cyclopentadiene in the presence of 10 mol% of 406 to give cycloadduct 405 with up to 91% ee (equation 120)252. 

The catalyst was prepared from the corresponding chiral diol and TiCl2(OPr-/)2 at room temperature in the presence of 4 A molecular sieves. Without molecular sieves, stoichiometric amounts of the titanium complex were required to obtain an equally high enantioselectivity. A remarkable solvent effect was observed. Various cycloadducts were only obtained with high optical yields when non-polar solvents were employed252,253. For example, 4-substituted 4-cyclohexene-1,2-dicarboxylate derivatives 408 were obtained with ee values ranging from 91 to 94% in the reactions of 91a, 399 and 407 with 17b in toluene/... 

Engler and colleagues256 demonstrated that the way in which catalyst 406 is prepared has a strong effect on the regioselectivity and enantioselectivity of quinone Diels-Alder reactions. The most effective catalyst was prepared from a 1 1 1 mixture of titanium tetrachloride, titanium tetraisopropoxide and chiral diol 416. The cycloadditions of 2-methoxy-l,4-benzoquinones such as 414 with simple dienes to give adducts like 415 proceeded with high yields and enantioselectivities of up to 80% ee using this catalytic system (equation 123). 

Another interesting example involves the dihydrosilylation of alkynes [20], which is carried out at room temperature in two steps, the first one with platinum chloride (0.01%) and the second one with palladium-MOP catalysts (0.3%). The reaction can be done with solely the palladium catalyst, but in that case the yield for the first step is low. The work-up leads to the formation of a chiral diol in high optical yield when the MOP derivative shown is used (Figure 18.12). 

The role of multicomponent ligand assembly into a highly enantioselective catalyst is shown in the enantioselective catalysis for the carbonyl-ene reaction (Table 8.9). The catalyst is prepared from an achiral precatalyst, Ti(0 Pr)4 and a combination of BINOL with various chiral diols such as TADDOL and 5-Cl-BIPOL in a molar ratio of 1 1 1 (10mol% with respect to the olefin and glyoxylate) in... 

In the catalytic system shown in Scheme 9, a hydrogen bond between one hydroxy function of the diol catalyst and the carbonyl group of the substrate is regarded as the driving force of catalysis. Here, the spatial orientation of the bulky a-1-naphthyl substituents of the TADDOL (a,a,a, a -tetraaryl-l,3-dioxolan-4,5-dimethanol) scaffold generates the chiral environment controlling the enantioselectivity of the reaction. 

As with the Diels-Alder reaction, it is possible to achieve enantioselective cycloaddition in the presence of chiral catalysts.89 The Ti(IV) catalyst C with chiral diol ligands leads to moderate to high enantioselectivity in nitrone-alkene cycloadditions.90... 

The Rawal group next applied diol catalysis to the enantioselective vinylogous Mukaiyama aldol (VMA) reaction of electron-deficient aldehydes [105]. Screening of various known chiral diol derivatives, including VANOL, VAPOL, BINOL, BAMOL, and TADDOL, revealed that 38a was the only catalyst capable of providing products in acceptable levels ofenantioselection (Scheme 5.55). Subsequent to this work, Scettri reported a similar study of TADDOL-promoted VMA reactions with Chan s diene [106]. 

SCHEME 79. Asymmetric epoxidation of olefins by TBHP catalyzed by a molybdenum catalyst in the presence of chiral diols... 

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

Heterogeneous asymmetric hydrogenation of 1,3-diketones is achieved by using a chirally modified Raney Ni catalyst (Scheme 1.51) [241]. Desired chiral diols are obtainable with about 90% ee. This method has been used for the synthesis of some naturally occurring compounds [242],... 

With Tartrate-Derived Chiral 1,4-Diol/Ti Complexes A catalytic asymmetric Diels-Alder reaction is promoted by the use of a chiral titanium catalyst prepared in situ from (Pr O TiC and a tartrate-derived (2.R,3.R)-l,l>4,4-tetraphenyl-2,3-0-(l-phenylethylidene)-l,2,3,4-butanetetrol. This chiral titanium catalyst, developed by Narasaka, has been successfully executed with oxazolidinone derivatives of 3-borylpropenoic acids as P-hydroxy acrylic acid equivalents [40] (Eq. 8A.21). The resulting chiral adduct can be utilized for the first asymmetric total synthesis of a highly oxygenated sesquiterpene, (-i-)-Paniculide. 

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