Diels-Alder reactions chiral reagents

Nishiyama H., Motoyama Y. Other Transition Metal Reagents Chiral Transition-Metal Lewis Acid Catalysis for Asymmetric Organic Synthesis in Lewis Acid Reagents 1999 225, Ed Yamamoto H., Pb. Oxford Univ. Press, Oxford Keywords asymmetric Diels-Alder reactions, chiral transition metal Lewis-acid catalysis, asymmetric synthesis... 

Keywords asymmetric Diels-Alder reactions, chiral titanium reagent... 

Another chiral titanium reagent, 11, was developed by Corey et al. [17] (Scheme 1.24). The catalyst was prepared from chiral ris-N-sulfonyl-2-amino-l-indanol and titanium tetraisopropoxide with removal of 2-propanol, followed by treatment with one equivalent of SiCl4, to give the catalytically-active yellow solid. This catalyst is thought not to be a simple monomer, but rather an aggregated species, as suggested by NMR study. Catalyst 11 promotes the Diels-Alder reaction of a-bro-moacrolein with cyclopentadiene or isoprene. 

With few exceptions chiral Lewis acids are usually moisture-sensitive and require anhydrous conditions, but bench-stable aquo complexes such as [Cu(S,S)-t-Bu-box)(H20)2](SbF6)2 were found to promote the Diels-Alder reaction as effectively as the anhydrous copper reagent. 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

Although furan is usually a poor diene in the Diels-Alder reaction, the chiral copper reagent 24b promotes its asymmetric addition to acryloyloxazolidinone to afford the 7-oxabicyclo[2.2.1]hept-2-ene derivative in high optical purity (Scheme 1.40). Because a retro-Diels-Alder reaction occurs above -20 °C, the reaction must be performed at low temperature (-78 °C) to obtain a high optical yield. The bicy-... 

The chiral copper reagent 24 is an effective catalyst not only for intermolecular, hut also for intramolecular Diels-Alder reactions, as shown in the following schemes (Scheme 1.41, 1,42, 1.43). Synthetically useful octalin and decalin skeletons were synthesized in high enantio- and diastereoselectivity. The synthetic utility of this intramolecular Diels-Alder reaction has been demonstrated hy a short total synthesis of isopulo upone [23, 33d]. 

Application of this catalytic process was extended to asymmetric intramolecular Diels-Alder reactions. Synthetically useful intermediates with octalin and decalin skeletons were obtained in high optical purity by use of a catalytic amount of the chiral titanium reagent [45] (Scheme 1.57, Table 1.25). The core part of the mevi-nic acids was enantioselectively synthesized by use of this asymmetric intramolecular reaction [46] (Scheme 1.58). 

Several highly enantioselective Diels-Alder reactions are known for which the di-enophile does not fit any of the above classes. Corey and coworkers applied the chiral aluminum reagent 36 with a C2-symmetric stilbenediamine moiety (videsu-pra) to the Diels-Alder reaction of maleimides as dienophiles [54] (Scheme 1.68). In most asymmetric Diels-Alder reactions the reactants are usually relatively simple dienes such as cyclopentadiene or monosubstituted butadienes, and unsym-... 

In contrast, modest enantioselection has been observed in the asymmetric Diels-Alder reaction between cyclopentadiene (18) with methylacrylate and methylpropiolate catalyzed by chiral organoaluminum reagents 58 [59] (Equation 3.15) prepared from trimethylaluminum and (R)-(+)-3,3 -bis(triphenylsi-lyl)-l,l -bi-2-naphthol [60]. The reaction was highly cnJo-diastereoselective. 

Keywords chiral boron reagents, Diels-Alder reaction, stereoselective... 

In 2005, another class of chiral ligands, bis(thiazolines) derivatives, was prepared by Nishio et al. from chiral bis-(A-acylamino alcohols) by using Lawesson s reagent. These new compounds have proved to be useful chiral ligands for the Zn-catalysed Diels-Alder reaction of 3-acryloyloxazolidine-2-one with cyclopentadiene, giving the corresponding cycloadducts as a 94 6 diastereomeric mixture, where the major diastereomer was formed with 92% ee (Scheme 5.14). 

For acrylates, or type I reagents, applied in asymmetric Diels-Alder reactions, several chiral auxiliaries such as menthol derivatives, camphor derivatives,16,3 and oxazolidinones4 are available. Carbohydrate compounds have also been reported as chiral auxiliaries in a recent publication, although the stereoselectivity was not good.5 Here are examples in which asymmetric Diels-... 

Chiral a,/ -unsaturated A-acyloxazolidinones have been regarded as a complement for type I dienophile reagents. Evans et al.4 reported a Diels-Alder reaction promoted by dialkyl aluminum chloride. In this reaction, chiral a,/ -unsaturated A-acyloxazolidinones were used as highly reactive and diaster-eoselective dienophiles. The stereogenic outcome of the Diels-Alder adducts... 

Lewis acids of chiral metal aryloxides prepared from metal reagents and optically active binaphthol derivatives have played a significant role in asymmetric synthesis and have been extensively studied.23 However, in Diels-Alder reactions, the asymmetric induction with chiral metal aryloxides is, in most cases, controlled by steric interaction between a dienophile and a chiral ligand. This kind of interaction is sometimes insufficient to provide a high level of enantioselectivity. 

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... 

The Diels-Alder reactions of the chiral reagents A-allyl-o-butylanilide and A -(o-butylphenyl)-2-methylmaleimide proceed with high endo and diastereofacial selectivity. ... 

Discrimination of the racemic aluminum reagent 4 can be carried out using chiral ketone 5, which deactivates one enantiomer of racemic 4. The hetero-Diels-Alder reaction is then catalyzed by the remaining opposite enantiomer of racemic 4 (Scheme 8.4). The combination of racemic 4 and chiral ketone 5 in a 1 1 ratio gives better enantiomeric excess than in a 2 1 ratio, implying that one diastereomer of the 4/5 complex readily dissociates to yield optically pure 4 and the chiral ketone 5. 

The chiral dialuminum Lewis acid 14, which is effective as an asymmetric Diels-Alder catalyst, has been prepared from DIBAH and BINOL derivatives (Scheme 12.12). " The catalytic activity of 14 is significantly greater than that of monoaluminum reagents. The catalyst achieves high reactivity and selectivity by an intramolecular interaction of two aluminum Lewis acids. Similarly, the chiral trialuminum Lewis acid 15 is quantitatively formed from optically pure 3-(2,4,6-triisopropylphenyl)binaphthol (2 equiv) and MeaAl (3 equiv) in CH2CI2 at room temperature (Scheme 12.12). " The novel structure of 15 has been ascertained by NMR spectroscopic analysis and measurement of the methane gas evolved. Trinuclear aluminum catalyst 15 is effective for the Diels-Alder reaction of methacrolein with cyclopentadiene. Diels-Alder adducts have been obtained in 99% yield with 92% exo selectivity. Under optimum reaction conditions, the... 

One of the efficient method for constructing carbohydrates is the Diels-Alder reaction, which gives a variety of important synthetic intermediates for the synthesis of cyclitol derivatives. We therefore were interested in the development of asymmetric Diels-Alder reaction by the use of chiral titanium reagents. 

Since high enantioselectivity was achieved by employing two molar equivalents of the chiral titanium reagent generated from 17b, the asymmetric Diels-Alder reaction of various oxazolidone derivatives of a,8-unsaturated acids and cyclopentadiene was studied. The results are listed in Table 4. With the exception of the acryloyl derivative 15b, various dienophiles reacted with cyclopentadiene to give the endo-adducts 1 in high optical purity. 

The a-pyrone (635) undergoes an exothermic Diels-Alder reaction with 1-diethylamino-1-propyne to afford the cycloadduct (636) (77JOC2930). Only a single regioisomer is produced, which is in line with the expected polarization of these reagents (Scheme 144). A Diels-Alder reaction of the same a-pyrone with 1-dibenzylamino-l-propyne affords an aniline derivative which has been employed in a chiral synthesis of the aromatic portion of the ionophore antibiotic lasalocid (80JA6178). 

Oppolzefs chiral auxiliary,6 (-)-2,10-camphorsultam, is useful in the asymmetric Diels-Alder reaction,3 4 and for the preparation of enantiomerically pure p-substituted carboxylic acids7 and diols,8 in the stereoselective synthesis of A2-isoxazolines,9 and in the preparation of N-fluoro (-)-2,10-camphorsultam, an enantioselective fluorinating reagent.10... 

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