Chiral, asymmetric polymerization

A most interesting extension of this type of reaction was performed by Addadi and Lahav (175). Their aim was to obtain chiral polymers by performing die reaction in a crystal of chiral structure. They employed monomers 103. The initial experiments were with a chiral resolved 103 where R1 is (R)- or ( -sec-butyl and R2 is C2H3. This material indeed crystallizes in the required structure, and yields photodimers and polymers with the expected stereochemistry, and with quantitative diastereomeric yield. It was possible to establish that the asymmetric induction was due essentially only to the chirality of the crystal structure and not to direct influences of the sec-butyl. Subsequently they were able, using sophisticated crystal engineering, to obtain chiral crystals from nonchiral 103, and from them dimers and polymers with high, probably quantitative enantiomeric yields. This may be described as an absolute asymmetric polymerization. 

The polymerization of trans-1,3-pentadiene, 149, in a chiral channel inclusion complex with enantiomerically pure perhydrotriphenylene affords an optically active polymer, 150 (236). Asymmetric polymerization of this monomer guest occurs also in deoxycholic acid inclusion complexes (237). 

The main limitation of these CSPs is their limited pressure stability, which makes them not very suitable for HPLC application. However, they have proved to be an excellent tool for the preparative separation of drugs by low-pressure HPLC. To make these CSPs accessible to HPLC, silica gel-based phases were developed. " This type of phase is available from Merck (Darmstadt, Germany) under the name Chiraspher. Polymer phases of different types have been developed by Okamoto s group. > They are prepared by the asymmetric polymerization of triphenylmethyl-methacrylate monomers. The original character of these polymers is that they do not possess any chiral centre and therefore their chirality is only due to their helicity. However, clear mechanisms have not been proposed... 

The enantioselective addition of an allylsilane to an aldehyde catalyzed by chiral acyloxyborane (CAB) 13 is an excellent method for obtaining optically active homoallyl alcohols.Itsuno and Kumagai reported that the synthesis of a new optically active polymer with chirality on the mainchain is possible by applying this reaction to the asymmetric polymerization of bis(allylsilane) and dialdehyde (Scheme 12.11). ... 

In the polymer field, reactions of this type are subject to several limitations related to the structure and symmetry of the resultant polymers. In effect, the stereospecific polymerization of propylene is in itself an enantioface-diflferen-tiating reaction, but the polymer lacks chirality. As already seen in Sect. V-A there are few intrinsically chiral stractures (254) and even fewer that can be obtained from achiral monomers. With two exceptions, which will be dealt with at the end of this section, optically active polymers have been obtained only from 1- or 1,4-substituted butadienes, fiom unsaturated cyclic monomers, fiom substituted benzalacetone, or by copolymerization of mono- and disubstituted olefins. The corresponding polymer stmctures are shown as formulas 32 and 33, 53, 77-79 and 82-89. These processes are called asymmetric polymerizations (254, 257) the name enantiogenic polymerization has been recently proposed (301). 

Asymmetric induction and stereoregularity can be treated, at least in part, as two distinct phenomena however, it has been observed that the values of pu and Pol can be divided into two parts one dependent on chiral factors external to the chain (catalyst, environment, etc.) and the other dependent on the intramolecular chain induction. This latter is a factor of stereoregularity or cooper-ativity rather than of chirality (its value is identical for both the DD and LL successions) (328). Both factors can be expressed as differences of free energies of activation In favorable cases, when they are of the same sign, asymmetric polymerization becomes easier (i.e., under the same conditions it gives a higher optical yield) than an analogous nonmacromolecular asymmetric synthesis. 

Another result of great importance—the conformational asymmetric polymerization of triphenylmethyl methacrylate realized in Osaka (223, 364, 365)— has already been discussed in Sect. IV-C. The polymerization was carried out in the presence of the complex butyllithium-sparteine or butyllithium-6-ben-zylsparteine. The use of benzylsparteine as cocatalyst leads to a completely soluble low molecular weight polymer with optical activity [a]o around 340° its structure was ascertained by conversion into (optically inactive) isotactic poly(methyl methacrylate). To the best of my knowledge this is the first example of an asymmetric synthesis in which the chirality of the product derives finom hindered rotation around carbon-carbon single bonds. 

Note l An asymmetric polymerization generally produces a polymer which contains chirality centres of opposite configuration in unequal amounts. 

Asymmetric polymerization in which the polymer molecules formed contain one (or more) new type(s) of elements of chirality not existing in the starting monomer(s). 

Polymerization of the bulky monomer chloral yields an optically active product when one uses a chiral initiator, e.g., lithium salts of methyl (+)- or (—)-mandelate or (R)- or (S)-octanoate [Corley et al., 1988 Jaycox and Vogl, 1990 Qin et al., 1995 Vogl, 2000], The chiral initiator forces propagation to proceed to form an excess of one of the two enantiomeric helices. The same driving force has been observed in the polymerization of triphenyl-methyl methacrylate at —78°C in toluene by initiating polymerization with a chiral complex formed from an achiral initiator such as n-butyllithium and an optically active amine such as (+)-l-(2-pyrrolidinylmethyl)pyrrolidine [Isobe et al., 2001b Nakano and Okamoto, 2000 Nakano et al., 2001]. Such polymerizations that proceed in an unsymmetrical manner to form an excess of one enantiomer are referred to as asymmetric polymerizations [Hatada et al., 2002]. Asymmetric polymerization has also been observed in the radical... 

Natta carried out the anionic polymerization of methyl sorbate, a 1,3-diene, with an optically active initiator and obtained an optically active homopolymer with main-chain chirality. The high molecular weight crystalline polymer produced with (P)-2-methylbutyllithium had a tritactic (di-iso-rra/w-tactic) structure. This was probably the first metal-catalyzed asymmetric polymerization 134). Polymerization of other dienes was attempted by using various asymmetric methods 135). 

Anionic Catalysis Several bulky methacrylates afford highly isotactic, optically active polymers having a single-handed helical structure by asymmetric polymerization. The effective polymerization mechanism is mainly anionic but free-radical catalysis can also lead to helix-sense-selective polymerization. The anionic initiator systems can also be applied for the polymerization of bulky acrylates and acrylamides. The one-handed helical polymethacrylates show an excellent chiral recognition ability when used as a chiral stationary phase for high-performance liquid chromatography (HPLC) [97,98]. 

Type II sorbents are based on an inclusion mechanism. Chiral recognition by optically active polymers is based solely on the helicity of that polymer. Optically active polymers can be prepared by the asymmetric polymerization of triphenylmethyl methacrylate using a chiral anionic initiator [264]. Helical polymers are unique from the previously discussed chromatographic approaches because polar functional groups are not required for resolution [265]. These commercially available sorbents have been used to resolve enantiomers of a-tocopherol [266]. The distinction between this group (lib) and the sorbents containing cavities is vague (Ila). 

Asymmetric Polymerization. The chiral organoaluminum catalyst is utilized for asymmetric polymerization of racemic a-methyl and p-methyl p-lactones. Optically active polymers pos-... 

A number of CSPs have been developed that are based on optically active synthetic helices formed by the asymmetric polymerization of methacrylate monomers. These polymers have been formed using either chiral monomers such as (S)-acryloylphenyl-alanine (73) and N-methylacryloyl-(S)-cyclohexylethylamine (73), or achiral monomers such as triphenyl methacrylate (74) and diphenyl-2-pyridyl-methyl methacrylate (74). In the latter case, the polymers were prepared using chiral cation catalysts including (—)-spartene-butyllithium and (+)-6-benzylsparteine-butyllithium complexes (74). The commercially available forms of these CSPs are listed in Table 3. 

In our work directed at achieving asymmetric polymerization we thus concentrated on non-chiral molecules of the type illustrated in Scheme 2 and, by correlating the space symmetry of the reactant with the point group of the possible product, we tried to generate all the hypothetical chiral motifs which, upon reaction, would give rise to chiral polymers. ... 

To explore the possibility of recycling alkaloid-Os04 complexes, several polymer-bound alkaloid derivatives have been used for heterogeneous catalytic asymmetric dihydroxylations. As chiral ligands, polymerized cinchona alkaloids or copolymers of quinine derivatives with acrylonitrile or styrene were studied [46]. In general, lower select vities and decreased rates were observed. 

Chiral an a-metallocene complexes have become useful catalysts in asymmetric polymerization reactions [73]. While enantio-resolution of a <3-metaIlocene race-mates cannot yield more than 50% of a particular enantiomer, the readily accessible racemate of a biphenyl-bridged metallocene complex (we abbreviate to bi-phecp -M M = Ti, Zr) has been quite recently reported to give enantio-pure ansa-titanocene and -zirconocene complexes through binol-induced asymmetric trans-... 

Yoshio Okamoto was born in Osaka, Japan, in 1941. He received his bachelor (1964), master (1966), and doctorate (1969) degrees from Osaka University, Faculty of Science. He joined Osaka University, Faculty of Engineering Science, as an assistant in 1969, and spent two years (1970— 1972) at the University of Michigan as a postdoctoral fellow with Professor C. G. Overberger. In 1983, he was promoted to Associate Professor, and in 1990 moved to Nagoya University as a professor. His research interest includes stereocontrol in polymerization, asymmetric polymerization, optically active polymers, and enantiomer separation by HPLC. He received the Award of the Society of Polymer Science, Japan, in 1982, the Chemical Society of Japan Award for Technical Development in 1991, the Award of The Chemical Society of Japan (1999), and the Chirality Medal (2001), among others. 

We published a review paper in this journal entitled Asymmetric Polymerization in 1994 which encompassed this aspect of helical polymer synthesis in addition to the other types of polymerization in which chirality is introduced during the polymerization process.34 There have been several other review papers on asymmetric polymerization and chiral polymers.35-40 On the other hand, if the energy barrier is low enough to allow rapid helix inversion at room temperature, one cannot expect to obtain a stable one-handed helical polymer but may expect to induce a prevailing helical sense with a small amount of chiral residue or stimulant. The existence of this type of polymer was most clearly demonstrated with poly(alkyl isocyanate)s.23,41... 

The significant contribution by the Nolte and Drenth group in this area was that, for the first time, they demonstrated the existence of a non-racem-ic helical structure for poly(isocyanide)s. Optical resolution using a chiral HPLC technique or asymmetric polymerization led to the isolation of optically active polymers, whose chirality was supposed to be solely due to the main chain helicity. Their effort, in conjunction with that of Novak s and Takahashi s significant contributions to asymmetric polymerization, will be discussed in the next section. Non-asymmetric and asymmetric polymerizations will be described separately in the following sections. 

The following subsections describe the asymmetric polymerization of isocyanides using four classifications based upon the mechanism of the asymmetric induction. The first two subsections deal with homo- and copolymerization of chiral, non-racemic isocyanides, and asymmetric polymerization of achiral isocyanides by chiral enantiopure nickel complexes are described in the final two subsections. 

In Nolte and Drenth s nickel catalyzed system, the polymerization was believed to be initiated by a nucleophilic attack by the alcohol used as a solvent or the halide on the starting complex on the coordinated isocyanides. Successful asymmetric polymerization was achieved using a dicationic tetrakis(isocyanide)nickel(II) complex 46 with enantiopure primary amines, which served as a chiral nucleophile in the initial step (Scheme 35) [58, 59]. In a typical experiment, a catalyst prepared from (f-BuNC)4Ni(II)(C104)2 (46a) (1 mol%) and an optically active amine (1 mol%), was used for polymerization of isocyanides with, or without a solvent, such as n-hexane, in... 

The details of this mechanism are still unclear, and need to be clarified. However, this asymmetric polymerization system using a nickel catalyst with optically active amines seems to be unique, in that the chiral elements that become apart from the propagating termini control the helical sense of the entire polymer main chain. A similar, but more stereoselective system is discussed below for the Pd-mediated polymerization of diisocyanobenzenes, which is discussed later. 

Chiral organopalladium complexes have been designed as initiators in the asymmetric polymerization of 1,2-diisocyanobenzenes instead of the resolved oligoquinoxalinylpalladium complexes. The first series of chiral initiators examined were the organopalladium complexes 98a-d bearing chiral 1,1 -binaphthyl groups (Scheme 57) [99, 100]. They were prepared from... 

Table 5 Asymmetric polymerization of diisocyanobenzenes 86 and 88 using chiral initiators 98a-d...

More recently, a series of new chiral palladium initiators 101-103 have been developed for the asymmetric polymerization of diisocyanobenzenes (Scheme 59) [101]. The new initiators are easily prepared from o-iodoben-... 

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