Asymmetric pericyclic reaction

Asymmetric Pericyclic Reactions. Several reports illustrate the utility of fra/is-2,5-dimethylpyirolidine as a chiral auxiliary in asymmetric Claisen-type rearrangements, [4 + 2], and [2 + 2] cycloaddition reactions. The enantioselective Claisen-type rearrangement of N,0-ketene acetals derived from tram-2,5-dimethylpyrrolidine has been studied. For example, the rearrangement of the iV.O-ketene acetal, formed in situ by the reaction of A-propionyl-fra/w-(25,55)-dimethylpyrrolidine with ( )-crotyl alcohol, affords the [3,3]-rearrangement product in 50% yield and 10 1 diastereoselectivity (eq 9). 

Asymmetric pericyclic reaction represents one of the most straightforward protocols to access enantioenriched cyclic compounds and triggers continuing interest in organic synthesis. Fruitful results have been achieved by the catalysis of chiral metal complexes over the past decades [1], On the other hand, recently small organic molecules have also contributed a lot to this area owing to the rapid development of asymmetric organocatalysis [2]. 

This chapter has been organized into sections based on the major reaction types. Hence, the hetero-Diels-Alder reaction has been included as a subsection of the Diels-Alder reaction. Although there are numerous reports of asymmetric pericyclic reactions, our discussion concentrates on reactions that are most likely to allow for scale up. 

Especially when combining two or more pericyclic reactions with each other, the outcome is highly efficient and could be almost qualified as miraculous, as each cycloaddition event could introduce a new ring, two new covalent bonds, and up to four new contiguous asymmetric centers in one step. Moreover, great progress has been achieved in the intramolecular and asymmetric pericyclic reactions recently, which provide highly effective approaches for the rapid elaboration of complex polycyclic systems. Some prominent total syntheses achieved based on pericyclic MBFTs will be exemplified below. 

It has been established that the course of the sequential pericyclic reaction of cyclopentadienones with acyclic conjugated alkadienes depends on the reaction temperature, thermal treatment at low temperatures affording 3a,4,7,7a-tetrahydroinden-l-one derivatives by way of a Cope rearrangement (see Scheme 38). Roman et al have developed an efficient stereoselective synthesis of enantiomerically pure i-nitrotricyclo[5.2.2.0 ]undeca-3,8-dienes via a tandem consecutive asymmetric Diels-Alder-Cope rearrangement (see Scheme 39). Adducts... 

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

The Diels-Alder reaction, a pericyclic reaction between a diene and a dienophile, is of utmost importance in synthetic organic chemistry. In the case of a reaction between asymmetrically substituted dienes (I) and asymmetrical dienophiles (II) ... 

Enamine catalysis involves a catalytically generated enamine intermediate that is formed via deprotonation of an iminium ion and that reacts with various electrophiles or undergoes pericyclic reactions. The first example of asymmetric enamine catalysis is the Hajos-Parrish-Eder-... 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

The Diels-Alder reaction of a diene and a dienophile has become one of the most powerful carbon-carbon bond-forming processes [81]. In normal Diels-Alder reactions of an electron-poor dienophile with an electron-rich diene, the main interaction is between the HOMO of the diene and the LUMO of the dienophile. Coordination of a Lewis acid to the dienophile reduces its frontier orbital energies, and this increases the rate of the reaction. Regio- and stereoselectivity are also markedly affected by the Lewis acid. Recent extensive studies on the design of chiral Lewis acids have led to fruitful results in the control of the stereochemistry of a variety of pericyclic reactions. Several chirally modified Lewis acids have been developed for the asymmetric Diels-Alder reaction [82,83] and spectacular advances have recently been achieved in this area. Various kinds of polymer-supported chiral Lewis acid have also been developed. Polymer-supported A1 Lewis acids such as 62 have been used in the Diels-Alder reaction of cyclopentadiene and methacrolein (Eq. 20) [84] as has polymer-supported Ti alkoxide 63 [84]. These Ti catalysts are readily prepared and have high activity in the Diels-Alder reaction. 

Other sections of this chapter should be accessed as many chiral auxiliaries and catalysts appear to cross over from one type of pericyclic reaction to another. It should also be noted that although a large number of pericyclic reactions are known, large differences in asymmetric induction can occur with only subtle changes in reagents. This is especially true of the Diels-Alder reaction. 

Aluminum-Carbonyl Complexation, Activation, and Nucleophilic Reaction Pericyclic Reaction and Asymmetric Reaction... 

A commoner way to make heterocycles by pericyclic reactions is to use 1,3-dipolar cycloadditions. These often occur without catalysis and so are compatible with many other reactions. The starting material 182 for this asymmetric synthesis of swainsonine was derived from a natural sugar (chiral pool strategy, chapter 23). An exceptionally stereoselective Wittig reaction gave the Z-alkene 183 (chapter 15) and the alcohol was converted into the azide 184 with diphenylphos-phoryl azide.24... 

What is more, the asymmetric structure of the surface dimers in silicon and germanium causes a polarization of the double bond. Hence may occur a nucleophilic attack on the Ji -orbital and the formation of a rr-complex from the attacking, electron rich alkene and the electron-deficient end of the surface dimer. The subsequent addition leading to the final product is easy to take place then (Figure 6.43). Obviously this is not the concerted and symmetric mechanism typical of pericyclic reactions, which is also why the prohibition of a thermal reaction is by-passed. 

This chapter examines reactions that involve molecular rearrangements and cycloadditions. The use of these terms will not be restricted to concerted, pericyclic reactions, however. Often, stepwise processes that involve a net transformation equivalent to a pericyclic reaction are catalyzed by transition metals. The incorporation of chiral ligands into these metal catalysts introduces the possibility of asymmetric induction by inter-ligand chirality transfer. The chapter is divided into two main parts (rearrangements and cycloadditions), and subdivided by the standard classifications for pericyclic reactions e.g., [1,3], [2,3], [4-1-2], etc.). The latter classification is for convenience only, and does not imply adherence to the pericyclic selection rules. Indeed, the first reaction to be described is a net [1,3]-suprafacial hydrogen shift, which is symmetry forbidden if concerted. 

A very interesting thermal pericyclic reaction inside the asymmetric carcerand 51 was recently reported by Reinhoudt and co-workers. They studied the extrusion of SO2 and butadiene from incarcerated 3-sulfolene by mass spectrometry (Figure 9.15). " ... 

Pericyclic Reactions. Trimethylsilyldiazomethane reacts with chiral acrylates to create optically active A -pyrazolines via regioselective asymmetric [3+2] cycloaddition. Subsequent pro-todesilylation affords A -pyrazolines in good yields (eq 66). This procedure offers a convenient route to azaprolines. ... 

The E. possess several asymmetric centers. In nature they occur as mixtures of stereoisomers. For synthesis, see Ut. The biosynthesis proceeds non-enzymat-ically from a>-phenylpolyenynoic acids by pericyclic reactions (endiandrin cascade). ... 

In addition to the classical reactions, this book covers many techniques and reactions that have more recently gained wide use among practicing chemists. Molecular-orbital theory is introduced early and used to explain electronic effects in conjugated and aromatic systems, pericyclic reactions, and ultraviolet spectroscopy. Carbon-13 NMR spectroscopy is treated as the routine tool it has become in most research laboratories, and the DEPT technique is introduced in this edition. Many of the newer synthetic techniques are also included, such as asymmetric hydrogenation and epoxidation, use of sodium triacetoxyborohydride, Birch reduction, Swern oxidations, alkylation of 1,3-dithianes, and oxidations using pyridinium chlorochromate. 

New types of combined pericycHc reactions 13UK228. Organocatalytic asymmetric cycloaddition reaction of ketenes 12CJ057. Pericyclic [4+2] and [3+2] cycloaddition reactions of nitroarenes in heterocyclic synthesis 13KGS102. 

As shown in this chapter, asymmetric organocatalytic pericyclic reactions have turned out powerful tools for selective construction of molecular complexity, in particular for DA, HAD, and [3+2] cycloadditions. The large number of applications of the adducts from these reactions establish organocatalytic pericyclic reactions as useful standard tools in a synthetic chemist toolbox. Without a doubt, this class of reactions will continue to develop with several new challenges to be addressed and numerous of new exciting discoveries that will further expand the synthetic application of this class of reactions. 

A review of the use of electrocyclic reactions in synthesis has been presented" and of asymmetric electrocyclic reactions that result in diastereo- or enantio-selectivity selection as a consequence of the influence of a chiral component, be it substrate or catalyst, on the electrocyclic bond-forming process." Computational studies of 0 electrocyclic ring-opening reactions of 2-pyrone and 6-fluoro-2-pyrone are pseudoper-icyclic 6-fluoro-2-pyranol are a borderline case and 2-pyranol, pyran, and 6-fluoro pyran reactions are pericyclic in character." ... 

Building upon these concepts, this chapter firstly gives an insight into the modes of action of a selection of non-covalent chiral organocatalysts, employing chiral Brpnsted acid catalysis, chiral Brpnsted base catalysis, and chiral phase-transfer catalysis (PTC). Further sections of this chapter describe two separate case studies that aim to compare and contrast selected covalent and non-covalent strategies for achieving two distinct processes, acyl transfer reactions and asymmetric pericyclic processes. 

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