Allylic alcohols catalytic enantioselective

Asymmetric cyclization was also successful in the rhodium-catalyzed hydrosilylation of silyl ethers 81 derived from allyl alcohols. High enantioselectivity (up to 97% ee) was observed in the reaction of silyl ethers containing a bulky group on the silicon atom in the presence of a rhodium-BINAP catalyst (Scheme 23).78 The cyclization products 82 were readily converted into 1,3-diols 83 by the oxidation. During studies on this asymmetric hydrosilylation, silylrhodation pathway in the catalytic cycle was demonstrated by a deuterium-labeling experiment.79... 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

In 1980, Katsuki and Sharpless communicated that the epoxidation of a variety of allylic alcohols was achieved in exceptionally high enantioselectivity with a catalyst derived from titanium(IV) isopropoxide and chiral diethyl tartrate. This seminal contribution described an asymmetric catalytic system that not only provided the product epoxide in remarkable enantioselectivity, but showed the immediate generality of the reaction by examining 5 of the 8 possible substitution patterns of allylic alcohols all of which were epoxidized in >90% ee. Shortly thereafter. Sharpless and others began to illustrate the... 

O Connor, S.P. Catalytic, Enantioselective Cyclopropanation of Allylic Alcohols PhD Thesis, University of Illinois, Urbana-Champaign, 1993. 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

Several catalytic systems have been reported for the enantioselective Simmons Smith cyclopropanation reaction and, among these, only a few could be used in catalytic amounts. Chiral bis(sulfonamides) derived from cyclo-hexanediamine have been successfully employed as promoters of the enantioselective Simmons-Smith cyclopropanation of a series of allylic alcohols. Excellent results in terms of both yield and stereoselectivity were obtained even with disubstituted allylic alcohols, as shown in Scheme 6.20. Moreover, this methodology could be applied to the cyclopropanation of stannyl and silyl-substituted allylic alcohols, providing an entry to the enantioselective route to stannyl- and silyl-substituted cyclopropanes of potential synthetic intermediates. On the other hand, it must be noted that the presence of a methyl substituent at the 2-position of the allylic alcohol was not well tolerated and led to slow reactions and poor enantioselectivities (ee<50% ee). ... 

The majority of catalytic enantioselective allylation reactions involve the chiral Lewis-acid-catalysed additions of allylsilanes or allylstannanes to carbonyl compounds. Monothiobinaphthol has been used by Woodward et al. as a chiral promoter in the enantioselective catalytic allylation of aryl ketones with impure Sn(allyl)4, prepared from allyl chloride, air-oxidised magnesium and SnCl4. Therefore, the allylation of arylketones in these conditions was achieved very efficiently, since the corresponding allylic alcohols were formed in... 

The use of alkylhydroperoxides as epoxidizing agents for allylic alcohols under catalytic conditions was soon expanded into enantioselective epoxidation with use of the more mild titanium alkoxides in the presence of chiral tartaric esters116. As concerns the epoxidation of functionalized dienes, these now so-called Sharpless conditions [Ti(OPr )4, dialkyl tartrate, TBHP] have been utilized to enantioselectively epoxidize 1,4-pentadiene-... 

The Sharpless epoxidation is a popular laboratory process that is both enantioselective and catalytic in nature. Not only does it employ inexpensive reagents and involve various important substrates (allylic alcohols) and products (epoxides) in organic synthesis, but it also demonstrates unusually wide applicability because of its insensitivity to many aspects of substrate structure. Selection of the proper chirality in the starting tartrate esters and proper geometry of the allylic alcohols allows one to establish both the chirality and relative configuration of the product (Fig. 4-1). 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

More recently, Hartwig and coworkers reported iridium-catalyzed, asymmetric aminations of allylic alcohols in the presence of Lewis acid activators [103]. The addition of molecular sieves and Nb(OEt)5 or catalytic amounts of BPh3 activated the allylic alcohol sufficiently to allow allylic amination reactions to occur in high yield, branched-to-linear selectivity, and enantioselectivity (Scheme 29). Without the activators, only trace amounts of product were observed. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

This method has proven to be an extremely useful means of synthesizing enantiomerically enriched compounds. Various improvements in the methods for carrying out the Sharpless oxidation have been developed.48 The reaction can be done with catalytic amounts of titanium isopropoxide and the tartrate ester.49 This procedure uses molecular sieves to sequester water, which has a deleterious effect on both the rate and enantioselectivity of the reaction. Scheme 12.9 gives some examples of enantioselective epoxidation of allylic alcohols. 

Table 17) with two substituents in position C3 the oxygen transfer by the chiral hydroperoxides occurred from the same enantioface of the double bond, while epoxidation of the (ii)-phenyl-substituted substrates 142c,g,i resulted in the formation of the opposite epoxide enantiomer in excess. In 2000 Hamann and coworkers reported a new saturated protected carbohydrate hydroperoxide 69b , which showed high asymmetric induction in the vanadium-catalyzed epoxidation reaction of 3-methyl-2-buten-l-ol. The ee of 90% obtained was a milestone in the field of stereoselective oxygen transfer with optically active hydroperoxides. Unfortunately, the tertiary allylic alcohol 2-methyl-3-buten-2-ol was epoxidized with low enantioselectivity (ee 18%) with the same catalytic system . 

In 1980, Katsuki and Sharpless described the first really efficient asymmetric epoxidation of allylic alcohols with very high enantioselectivities (ee 90-95%), employing a combination of Ti(OPr-/)4-diethyl tartrate (DET) as chiral catalyst and TBHP as oxidant Stoichiometric conditions were originally described for this system, however the addition of molecular sieves (which trap water traces) to the reaction allows the epoxidation to proceed under catalytic conditions. The stereochemical course of the reaction may be predicted by the empirical rule shown in equations 40 and 41. With (—)-DET, the oxidant approaches the allylic alcohol from the top side of the plane, whereas the bottom side is open for the (-l-)-DET based reagent, giving rise to the opposite optically active epoxide. Various aspects of this reaction including the mechanism, theoretical investigations and synthetic applications of the epoxy alcohol products have been reviewed and details may be found in the specific literature . 

The metal-catalyzed asymmetric epoxidation of allylic alcohols with various enan-tiomerically pure hydroperoxides has been studied by several groups. This approach has been employed in the Ti- and V-mediated epoxidation of this class of substrates, in the presence of different achiral additives with modest enantioselectivities (ee ee < 46% ), which turned satisfactory (ee 72%) in the presence of the TADDOL-derived hydroperoxide TADOOH 73 . This oxidant has been recently employed in the oxovanadium sandwich-type POM [ZnW(V0)2(ZnW9034)2] catalyzed epoxidation of various allylic alcohols with very high catalytic efficiency (42000 turnovers) and enantiomeric ratios up to 95 5 98. 

They have also developed a catalytic version of the reaction in which the chiral ligand DIPT was used in 20 mol% (379-381). In spite of the reduction of the amount of the chiral ligand, enantioselectivities of up to 93% ee were obtained in this work. The addition of a small amount of 1,4-dioxane proved to be crucial for the enantioselectivity of the reaction. A proposal for the reaction mechanism is outlined in Scheme 12.88. Allyl alcohol, hydroximoyl chloride 274 and diethylzinc react to form 276, which is mixed with the ligand and an additional amount of... 

Asymmetric elimination of bicyclic wc.vr>-epoxides 3 to give the corresponding allyl alcohols (/ )-4 can be achieved in moderate yield and enantioselectivity by using vitamin B12, which is, in situ, reduced to catalytically active vitamin B12s [cob(I)alamin] with zinc in methanol68-70. This reaction fails for 1,2-epoxycyclooctane and also for monocyclic epoxides, e.g., 2,3-dimethyIoxi-rane gives (/ )-3-buten-2-ol in 57% yield but with low enantiomeric excess (26%)68-70. 

Conversely, Charette and coworkers have shown that the chiral phosphate 23 could be used in catalytic amounts for the cyclopropanation of protected allylic alcohols (equation 97) . This was made possible by using DME as the additive to slow down the background cyclopropanation process, leading to racemic cyclopropane (Pathway A). Bis(iodomethyl)zinc was used as the stoichiometric reagent to regenerate the reactive iodomethylzinc phosphate (Pathway B). Excellent enantioselectivities were observed using this protocol however, the scope of the reaction is still quite limited. 

This enantioselective preparation of allylic alcohols has been applied to the synthesis of the side chain of prostaglandins . The addition to functionalized aldehydes, such as 483, allows the synthesis of C2-symmetrical 1,4-diols, such as 484, with excellent diastereoselectivity and enantioselectivity . An extension of this method allows the synthesis of C3-symmetrical dioF . Aldol-type products result from the catalytic enantioselective addition of functionalized dialkylzincs to 3-TIPSO-substituted aldehydes, such as 485, followed by a protection-deprotection and oxidation sequence affording 486 in 70% yield and 91% ee (Scheme 118) . The addition to a-alkoxyaldehydes provides a... 

Dosa and Fu reported the first catalytic enantioselective phenyl transfer reaction to ketones (equation 25)100. In the presence of 1.5 equivalents of MeOH, the chiral tertiary alcohol was produced in good yield and with high enantioselectivity. Walsh and workers recently reported the Ti(OE -i Vchiral dihydroxybis(sulfonamide) catalyst 34 system, whereby enones have been converted to enantioenriched allyl alcohols101. 

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