Asymmetric catalysis cyclization

Throughout each chapter, clear structures, schemes, and figures accompany the text. Mechanism, reactivity, selectivity, and stereochemistry are especially addressed. Special emphasis is also placed on introducing both the logic of total synthesis and the rationale for the invention and use of important synthetic methods. In particular, we amplify the most important developments in asymmetric synthesis, catalysis, cyclization reactions, and organometallic chemistry. 

During cyclization with acetylene, the chiral center is maintained. This reaction has recently been extended to the synthesis of bipyridyl compounds having optically active substituents (75PC1) and provides access to chiral ligands of potential interest in transition-metal-catalyzed asymmetric catalysis. 

The chiral organolanthanides have been especially designed for asymmetric catalysis. Thus far several enantioselective olefin transformations (hydrogenation, hydroamination/cyclization, hydrosilylation) as well as the polymerization of methyl methacrylate mediated by these chiral organolanthanide metallocenes have been investigated. 

Experiments conducted in the mid-1980s by Agami indicated a small nonlinear effect in the asymmetric catalysis in the Hajos-Parrish-Wiechert-Eder-Sauer reaction (Scheme 6.7). Agami proposed that two proline molecules were involved in the catalysis the first proline forms an enamine with the side chain ketone and the second proline molecule facilitates a proton transfer. Hajos and Parrish reported that the proline-catalyzed cyclization shown in Scheme 6.7 did not incorporate when run in the presence of labeled water. While both of these results have since been discredited—the catalysis is first order in catalyst and is incorporated into... 

Planar chiral phosphaferrocene-oxazolines (379) constitute another family of complexes that are usefiil as ligands in asymmetric catalysis. Preparation of these takes advantage of a modified Friedel-Crafts acylation of (373) and an unusual conversion of the resulting trifluoromethyl ketone into an amide that is then cyclized to an oxazoline. The diastereomeric complexes thus formed are chromatographically separable and are used in a palladium-catalyzed asymmetric allylic substitution. Modification of this complex by using the anion derived from 3,4-dimethyl-2-phenylphosphole gives more... 

Ene Cyclization, " The asymmetric catalysis of the intramolecular carbonyl-ene reaction not only of type (3,4) but also (2,4) employs the BINOL-derived titanium complexes [(I )-BINOL-TiX2 X = C104 or OTf], modified by the perchlorate and trifluoromethanesulfonate ligands. The tmns-... 

Asymmetric catalysis of ene reactions was initially investigated for the intramolecular examples, because intramolecular versions are much more facile than their inter-molecular counterparts. The first reported example of an enantioselective 6-(3,4) car-bonyl-ene cyclization employed a BINOL-derived zinc reagent [81]. This, however, was successful only when excess zinc reagent (at least 3 equiv.) was used. An enantioselective 6-(3,4) olefin-ene cyclization has also been developed which uses a stoichiometric amount of a TADDOL-derived chiral titanimn complex (Sch. 26) [82]. In this ene reaction, a hetero Diels-Alder product was also obtained, the periselectivity depending critically on the solvent system employed. In both cases, geminal disubstitution is required of high ee are to be obtained. Neither reaction, however, constitutes an example of a truly catalytic asymmetric ene cyclization. 

We reported the first examples of asymmetric catalysis of intramolecular carbonyl-ene reactions of types (3,4) and (2,4) using the BINOL-derived titanium complex (1) [80,83]. The catalytic 7-(2,4) carbonyl-ene cyclization gives the oxepane with high ee, and gem-dimethyl groups are not required (Sch. 27). In a similar catalytic 6-(3,4) ene cyclization, the fram-tetrahydropyran is preferentially produced, with high ee (Sch. 28). The sense of asymmetric induction is exactly the same as observed for the glyoxylate-ene reaction—the (f )-BINOL-Ti catalyst provides the (R)-cyclic alcohol. 

Keck also investigated asymmetric catalysis with a BINOL-derived titanium complex [102,103] for the Mukaiyama aldol reaction. The reaction of a-benzyloxyalde-hyde with Danishefsky s dienes as functionalized silyl enol ethers gave aldol products instead of hetero Diels-Alder cycloadducts (Sch. 40) [103], The aldol product can be transformed into hetero Diels-Alder type adducts by acid-catalyzed cyclization. The catalyst was prepared from BINOL and Ti(OPr )4, in 1 1 or 2 1 stoichiometry, and oven-dried MS 4A, in ether under reflux. They reported the catalyst to be of BINOL-Ti(OPr% structure. 

Especially noteworthy is the field of asymmetric catalysis. Asymmetric catalytic reactions with transition metal complexes are used advantageously for hydrogenation, cyclization, codimerization, alkylation, epoxidation, hydroformylation, hydroesterification, hydrosilylation, hydrocyanation, and isomerization. In many cases, even higher regio- and stereoselectivities are required. Fundamental investigations of the mechanism of chirality transfer are also of interest. New chiral ligands that are suitable for catalytic processes are needed. 

Enantioselective intramolecular cyclization of secondary phosphines 216 or their boranes, catalyzed by chiral palladium(diphosphine) complexes, afforded P-stereogenic benzophospholanes 217 with moderate stereoselectivity (59-70% ee) and yields. However, the absolute configuration of compounds has not been established. This reaction allowed chiral phospholanes to be obtained, which are valuable ligands in asymmetric catalysis (Scheme 70) [115]. 

Chiral secondary amines have proven to be amongst the most dynamic and efficient of asymmetric catalysts. There are essentially two modes of activation by secondary amines whereby a nucleophilic enamine or an electrophilic imininm ion is generated. Figure 1.4 shows a generic scheme of these two modes of activation and how they would be used in asymmetric organocatalytic cyclizations. A third mode of catalysis, named Organo-SOMO catalysis is discussed in Sect 1.5.1.5. 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

As with many asymmetric processes, there are three ways to control absolute stereochemistry in the Nazarov cyclization Asymmetry transfer, the use of chiral auxiliaries, or asymmetric catalysis. It is important to realize, however, that there are two distinct processes operating that determine the stereochemistry of the product. To control the absolute stereochemistry of the p-carbon atom(s), it is necessary to control the sense of conrotation, clockwise or counterclockwise (torquoselectivity, see Section 3.4.3). To control the absolute stereochemistry of the a-carbon atom however, it is necessary to control the facial selectivity for enol protonation. 

Perhaps the most elegant and attractive method to control absolute stereochemistry, however, is the use of asymmetric catalysis, and several examples of this approach have been applied to the Nazarov cyclization. Traimer and co-workers were the first to report a single example of a successfiil asymmetric Nazarov cyclization catalyzed by chiral scandium complex in 2003. In the exact same issue of the journal however, Aggarwal and co-workers reported a more in-depth study using copper pyBOX complexes. ... 

Copper(I) catalysis has demonstrated its long-held reputation in asymmetric synthesis over the past decade. The moderate Lewis acidity and coordination property of Cu(l) salts make it a versatile metal center in various metal-ligand complex systems and thereby have broad applications in the area of organic chemistry, especially in the asymmetric catalysis field. This chapter summarizes the recent developments of Cu(l)-catalyzed asymmetric cycloaddition and cascade addition-cyclization reactions since 2010. A wide range of asymmetric transformations catalyzed by chiral Cu(l) complexes are discussed, such as the 1,3-dipolar cycloadditions, including [3+2], [3+3], and [3+6] cycloadditions. Other cycloadditions and cascade addition-cyclization reactions are also discussed. 

Transannular intramolecular Diels-Alder (TADA) cyclizations have been widely employed. Although a great deal has been learned about relative stereocontrol, little progress had been made on asymmetric catalysis of the cyclization of prochiral trienes such as 20. Eric N. Jacobsen of Harvard University has now found Science 2007, 317, 1736) that the o-fluoro complex 21 served effectively. The power of this approach was illustrated by the conversion of the adduct 22 into the natural product 11,12-diacetoxydrimane 23. 

In 2007, Gagne s group succeeded in a regio- and diastereoselective oxidative polycyclization of di- and trienols catalyzed achiral [(dppe)Pt] dications, wherein turnover was achieved by the trityl cation abstracting a hydride from a putative [(dppe)Pt-H] intermediate [32i]. One year later, Gagne s group developed the catalytic enantioselective polyene cyclization induced by [(S)-(xylyl-PHANEPHOS) Pt][(BF )j] catalyst, which was prepared from (S)-(xylyl-PHANEPHOS)PtIj and AgBF in situ (Scheme 9.21) [32j]. This asymmetric catalysis enables the oxidative cascade cyclization of polyalkene substrates [32k] (Scheme 9.15). 

This compilation embraces a wide variety of subjects, such as solid-phase and microwave stereoselective synthesis asymmetric phase-transfer asymmetric catalysis and application of chiral auxiliaries and microreactor technology stereoselective reduction and oxidation methods stereoselective additions cyclizations metatheses and different types of rearrangements asymmetric transition-metal-catalyzed, organocatalyzed, and biocatalytic reactions methods for the formation of carbon-heteroatom and heteroatom-heteroatom bonds like asymmetric hydroamina-tion and reductive amination, carboamination and alkylative cyclization, cycloadditions with carbon-heteroatom bond formation, and stereoselective halogenations and methods for the formation of carbon-sulfur and carbon-phosphorus bonds, asymmetric sulfoxidation, and so on. 

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