Aldehydes Diels-Alder reactions, chiral catalysis

The most frequently encountered, and most useful, cycloaddition reactions of silyl enol ethers are Diels-Alder reactions involving silyloxybutadicncs (Chapter 18). Danishefsky (30) has reviewed his pioneering work in this area, and has extended his studies to include heterodienophiles, particularly aldehydes. Lewis acid catalysis is required in such cases, and substantial asymmetric induction can be achieved using either a chiral lanthanide catalyst or an a-chiral aldehyde. 

A titanium complex derived from chiral /V-arencsulfonyl-2-amino-1 -indanol [20], a cationic chiral iron complex [21], and a chiral oxo(salen)manganese(V) complex [22] have been developed for the asymmetric Diels-Alder reaction of oc,P-unsaturated aldehydes with high asymmetric induction (Eq. 8A.11). In addition, a stable, chiral diaquo titanocene complex is utilized for the enantioselective Diels-Alder reaction of cyclopentadiene and a series of a.P Unsaturated aldehydes at low temperature, where catalysis occurs at the metal center rather than through activation of the dienophile by protonation. The high endo/exo selectivity is observed for a-substituted aldehydes, but the asymmetric induction is only moderate [23] (Eq. 8A. 12). 

Inanaga et al. have reported the preparation of the new chiral Yb(III) phosphate complex 180 (Figure 43), which is an efficient catalyst for asymmetric hetero-Diels-Alder reactions of 181 with aromatic aldehydes and/or a,P-unsaturated aldehydes. 2,6-Lutidine is found to be an effective additive to obtain high enantioselectivities.98 Another asymmetric catalysis for hetero-Diels-Alder reaction was reported by Mikami et al.99 An illustrative example is shown in Figure 44, wherein the interesting effects of water as an additive were observed to increase not only the enantioselectivity but also the chemical yield. 

As shown above, asymmetric catalysis of Diels-Alder reactions has been achieved by use of chiral titanium complexes bearing chiral diol ligands. Yamamoto has reported a chiral helical titanium complex derived from Ti(OPr )4 and a BINOL-derived tetraol ligand (Sch. 54) [134], The Diels-Alder products are obtained with uniformly high enantioselectivity, irrespective of the substituent pattern of a,/3-unsaturated aldehydes. Corey has also reported a new type of chiral titanium complex derived from an amino alcohol ligand (Sch. 55) [135]. The chiral titanium complex serves as an efficient asymmetric catalyst for the reaction of 2-bromoacrolein the Diels-Alder product is obtained with high enantioselectivity. 

Danishefsky and co-workers pioneered the use of chiral lanthanide complexes as catalysts in organic reactions. They found out that Eu(hfc)3, which is used as an NMR shift reagent, promoted hetero Diels-Alder reactions [30] of aldehydes with siloxydienes and induced enantiomeric enrichment (Sch. 1) [31]. Suitable substituents on the dienes were introduced to improve the extent of asymmetric induction. The best result was obtained in the reaction of benzaldehyde with l-methoxy-2-methyl-3-(trimethyl-siloxy)- , 3-butadiene using 1 mol % Eu(hfc)3 the enantiomerie excess was, however, moderate (58%). The authors maintained that the major advantage of lanthanide catalysis lay in the survival of otherwise labile systems used as adducts. 

Hetero Diels-Alder reactions between prochiral aldehydes and activated dienes such as 84 are also known to be catalyzed by Lewis acids (Eq. 26) and catalysis by chiral Lewis acids supported by dimethylpolysiloxane (83a) has been investigated [100]. Enantio-selectivity up to 43 % ee was achieved by use of polymeric Lewis acids. 

A mechanism has been proposed for the enantioselective Mikami ene reaction of a terminal alkene with a glyoxylic aldehyde using a chiral binaphthol as Lewis acid. Stereoselective synthesis of 5-amino esters via asymmetric aldol-type and aza-Diels-Alder reactions has been reviewed. Siliranes react cleanly with benzaldehyde to produce oxasilacyclopentanes—with inversion— under conditions of Bu OK catalysis enolizable aldehydes yield sdyl enol ethers. ... 

Chiral (helical) Lewis acids for asymmetric Diels-Alder catalysis are prepared from titanium tetraisopropoxide 5 and a chiral binaphthol ligand 4 [13]. The titanium reagent 6 plays an important role as chiral template for the fixation of a,fi-unsaturated aldehydes and thereby for the enantioface recognition of substrates. The asymmetric Diels-Alder reaction, e. g., of cyclopentadiene 7 and acrolein 8, is effected in the presence of catalytic (P)-6 (10 mol%), producing the endo adduct 9 (R =R2=H) in 88% ee (Scheme 1). 

The use of lanthanide complexes in asymmetric catalysis was pioneered by Danishefsky s group with the hetero-Diels-Alder reaction,and their utility as chiral Lewis acid catalysts was shown by Kobayashi. The Brpnsted base character of lanthanide-alkoxides has been used by Shibasaki for aldol reactions, cyanosilylation of aldehydes and nitroaldol reactions.The combination of Lewis acid and Brpnsted base properties of lanthanide complexes has been exploited in particular by Shibasaki for bifunctional asymmetric catalysis. These bimetallic lanthanide-main-group BINOL complexes are synthesized according to the following routes ... 

Catalysis of Diels-Alder Reactions. Me2AlCl has been used as a Lewis acid caUilyst for inter- and intramolecular Diels-Alder reactions with a wide variety of dienophiles. High diastereoselectivity is obtained from chiral a,p-unsaturated N-ticyloxazolidinones with more than 1 equiv of Me2AlCl. Use of MezAlCl as a catalyst affords high yields in inter- and intramolecular Diels-Alder reactions of a,p-unsaturated ketones (eq 1), and intramolecular Diels-Alder reactions of a, 3-unsaturated aldehydes. Me2AlCl-catalyzed Diels-Alder reac-... 

Catalysis of Diels-Alder Reactions. EtAlCb is a useful Lewis acid catalyst for Diels-Alder reactions. It is reported to be more efficacious for the Diels-Alder reaction of Acrolein and butadiene than either AICI3 or Et2AlCl. It is a useful catalyst for intramolecular Diels-Alder reactions with a,p-unsaturated esters (eq 4) and aldehydes as dienophiles. It has also proven to be a very efficient catalyst for the inter- and intramolecular asymmetric Diels-Alder reaction of chiral a,p-unsaturated acyl sultams (eq 5) and has been used to catalyze a wide variety of Diels-Alder... 

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. 

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