Precise Synthesis of Macromolecular Architectures by Novel Iterative Methodology Combining Living Anionic Polymerization with Specially Designed Linking Chemistry

Review Precise Synthesis of Macromolecular Architectures by Novel Iterative Methodology Combining Living Anionic Polymerization with Specially Designed Linking Chemistry

Raita Goseki 1,2,*, Shotaro Ito 1, Yuri Matsuo 1, Tomoya Higashihara 3 and Akira Hirao 1,4,5,*

1 Polymeric and Organic Materials Department, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1, Ohokayama, Meguro-ku, Tokyo 152-8552, Japan; sito@polymer.titech.ac.jp (S.I.); [email protected] (Y.M.) 2 Department of Chemical Science and Engineering, School of Materials Chemistry and Technology, Tokyo Institute of Technology, 2-12-1, Ohokayama, Meguro-ku, Tokyo 152-8552, Japan 3 Department of Polymer Science and Engineering, Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan; [email protected] 4 Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan 5 Department of Applied Chemistry, National Chiao Tung University, Hsinchu 30010, Taiwan * Correspondence: [email protected] (R.G.); [email protected] (A.H.); Tel.: +81-3-5734-2138 (R.G.)

Received: 26 August 2017; Accepted: 17 September 2017; Published: 25 September 2017

Abstract: This article reviews the development of a novel all-around iterative methodology combining living anionic polymerization with specially designed linking chemistry for macromolecular architecture syntheses. The methodology is designed in such a way that the same reaction site is always regenerated after the polymer chain is introduced in each reaction sequence, and this “polymer chain introduction and regeneration of the same reaction site” sequence is repeatable. Accordingly, the polymer chain can be successively and, in principle, limitlessly introduced to construct macromolecular architectures. With this iterative methodology, a variety of synthetically difﬁcult macromolecular architectures, i.e., multicomponent µ-star polymers, high generation dendrimer-like hyperbranched polymers, exactly deﬁned graft polymers, and multiblock polymers having more than three blocks, were successfully synthesized.

Keywords: living anionic polymerization; linking chemistry; µ-star polymer; high generation dendrimer-like hyperbranched polymer; exactly deﬁned graft polymers; multiblock polymers; iterative methodology; benzyl bromide; α-phenylacrylate

1. Introduction Macromolecular architectures generally involve graft, star-branched, and hyperbranched polymers [1–3]. In this article, multiblock polymers with more than three blocks linked in a line are also added, although they are not usually categorized in macromolecular architectures. These architectural polymers have attracted increasing interest year by year because of the formation of their unique and characteristic 3D long-range morphological nanostructures and supramolecular assemblies, which can be fabricated to make nano devices important in the ﬁelds of nanoscience and nanotechnology [4–14]. Since the method for forming such nanostructures and supramolecular assemblies is strongly dominated by their architectures, it is essential to synthesize the well-deﬁned macromolecular architectures.

Polymers 2017, 9, 470; doi:10.3390/polym9100470 www.mdpi.com/journal/polymers Polymers 2017, 9, 470 2 of 30

All of the synthetic methodologies so far developed are specifically designed based on the architectures [1–3]. In any case, synthetic difficulty and limitation are present because multistep reactions and several reaction sites with different reactivities selectively worked in linking reaction steps are always required. For this reason, the synthesis of macromolecular architectures has long been recognized to be very difficult and still challenging even now. To overcome the difficulty and limitation of systematically synthesizing macromolecular architectures, we have been developing a novel all-around iterative methodology combining living anionic polymerization with specially designed linking chemistry since the 1990s [15–20]. This methodology is designed in such a way that the same reaction site is always regenerated after the polymer chain introduction in each reaction sequence, and this “polymer chain introduction and regeneration of the same reaction site” sequence is repeatable. If the synthetic design operates as expected, the polymer chain can be successively, and in principle, limitlessly introduced to construct macromolecular architectures. One more important advantage of this methodology is that the use of multistep selective reactions and reaction sites with different reactivities generally required for macromolecular architecture synthesis can be completely avoided because the polymer segment is introduced one by one in each reaction step. This iterative methodology was first applied to the synthesis of mixed arm star polymers and found to be very successful. After that, the methodology has been widely applied to the syntheses of high generation dendrimer-like hyperbranched polymers, exactly defined graft polymers, and multiblock polymers with more than three blocks. Needless to say, these polymers are synthetically very difficult even now due to their complex architectures along with structural perfection. Herein, we report on the successful synthesis of well-defined complex macromolecular architectures by the novel all-around iterative methodology combining living anionic polymerization with specially designed linking chemistry.

2. Macromolecular Architecture Syntheses by Iterative Methodology

2.1. Star Polymers ((SP)s) The first successful macromolecular architecture synthesized by the all-around iterative methodology is a series of multicomponent (SP)s. Mixed arm (SP)s with a composition asymmetry (hereinafter, called “µ-star polymers (µ-SP)”), have recently attracted interest due to their unique morphologies on the basis of star-branched architecture [5,8,10–13,21–29]. However, the synthesis of well-defined (µ-SP)s with more than three different compositions is very difficult by two requirements: First, multistep selective reactions in a number that corresponds to all the different arms are required. Secondly, several reaction sites with different reactivities selectively operating for different arm introduction are required. For these requirements, the already reported methodologies using living anionic polymerization allow access only to the synthesis of two components AxBy and several ABC and ABCD (µ-SP)s [17,30–45]. Although a 5-arm ABCDE (µ-SP) was recently synthesized by the combination of living polymerization with azide-alkyne cycloaddition reaction [46], multicomponent (µ-SP) synthesis is quite limited even now. The first successful synthesis of multicomponent (µ-SP) by an iterative methodology is shown in Scheme1[ 47,48]. In the first reaction sequence, a living chain-end-X-functionalized polymer (A) was prepared by the end-capping of a living polymer (A) with an X-substituted 1,1-diphenylethylene (DPE). After the termination, the introduced X terminus was converted to a Y reaction site, which can react with a living polymer. A living chain-end-X-functionalized polymer (B) was prepared and in situ reacted with the resulting Y-functionalized polymer (A), thus forming an in-chain-X-functionalized diblock copolymer. After converting the X to Y reaction site, a newly prepared slightly excess amount of living chain-end-X-functionalized polymer (C) reacted with the Y-functionalized diblock copolymer to result in an ABC (µ-SP). The objective coupling product was isolated by fractional precipitation using appropriate solvent system or using preparative size exclusion chromatography (SEC). Similarly, an Polymers 2017, 9, 470 3 of 30

ABCD (µ-SP) was obtained by iterating the reaction sequence with a living chain-end-X-functionalized polymerPolymers 2017 (D)., 9, 470 3 of 31

(1) Arm introduction Br Y X (2) Regeneration of the same O-Si reaction site 1 a) Me3SiCl/LiBr

(A) X MeOH a) -H -H X X Y (B)

X a)

(2) (1) X Y (C)

X a) X Y (1) (2)

(D)

(1) a) X X Y (1) (2) (2)

SchemeScheme 1. (μ(-SP)µ-SP) synthesis synthesis by the by iterative the iterative methodology. methodology. Reproduced Reproduced with permission with permission from reference from reference[47]. Copyright [47]. Copyright 2005 American 2005 American Chemical Chemical Society. Society.

The living chain-end-X-functionalized polymer was prepared by end-capping a living anionic The living chain-end-X-functionalized polymer was prepared by end-capping a living polymer with 1-(3-tert-butyldimethylsilyloxymethylphenyl)-1-phenylethylene (1). The 3-tert- anionic polymer with 1-(3-tert-butyldimethylsilyloxymethylphenyl)-1-phenylethylene (1). The butyldimethylsilyloxymethylphenyl ω-terminus was quantitatively converted to the benzyl bromide 3-tert-butyldimethylsilyloxymethylphenyl ω-terminus was quantitatively converted to the benzyl (BnBr) reaction site with a 1:1 mixture of (CH3)3SiCl and LiBr. The results are summarized in Table 1. bromide (BnBr) reaction site with a 1:1 mixture of (CH3)3SiCl and LiBr. The results are summarized in All of the polymers possessed the well-controlled Mn values and compositions and extremely low Table1. All of the polymers possessed the well-controlled Mn values and compositions and extremely polydispersity indexes. The successful syntheses of the requisite ABC and ABCD (μ-SP)s are thus low polydispersity indexes. The successful syntheses of the requisite ABC and ABCD (µ-SP)s are obvious. thus obvious. As can be seen in Scheme 1, the reaction steps, (1) and (2), in each of all reaction sequences are equal to theTable “polymer 1. Characterization chain (arm results in this of (case)µ-SP)s introduction” synthesized by theand iterative the “regeneration methodology. of the same reaction site”. The living end-X-functionalized polymer plays as a key role in order to introduce both the arm and the X functionalityMn (kg/mol)in each sequence. SinceMw/M then finalComposition (μ-SP) still (wt has % the wt %X wtfunctionality %) Polymer convertible to the Y reactionCalcd. site, this RALLS procedurea enablesSEC further reaction Calcd. sequence.1H NMRThus, the first proposed iterativeA methodology 10.4 works 10.0very satisfactorily 1.02 as designed. 100 100 AB 19.8 20.8 1.02 50/50 48/52 3-armTable ABC 1. Characterization 31.7 results 34.4 of (μ-SP)s synthesized 1.02 by 32/34/34 the iterative methodology. 34/32/34 4-arm ABCD b 45.8 46.5 1.02 26/24/25/25 27/23/25/25 Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) a Polymer b Determined by SEC with RI, viscometer, anda right angle laser light scattering (RALLS) detector.1 A, B, C, and D arms correspondCalcd. to polystyrene,RALLS poly(α-methylstyrene),SEC poly(4-methylstyrene), Calcd. andH NMR poly(methyl methacrylate),A respectively.10.4 10.0 1.02 100 100 AB 19.8 20.8 1.02 50/50 48/52 3-arm ABC 31.7 34.4 1.02 32/34/34 34/32/34 As can be seen in Scheme1, the reaction steps, (1) and (2), in each of all reaction sequences 4-arm ABCD b 45.8 46.5 1.02 26/24/25/25 27/23/25/25 are equal to the “polymer chain (arm in this case) introduction” and the “regeneration of the same a Determined by SEC with RI, viscometer, and right angle laser light scattering (RALLS) detector. b A, reaction site”. The living end-X-functionalized polymer plays as a key role in order to introduce both B, C, and D arms correspond to polystyrene, poly(α-methylstyrene), poly(4-methylstyrene), and poly(methyl methacrylate), respectively.

The DPE derivative, 1, is capable of not only reacting with a living polymer but also of offering the X function. Thus, the use of 1 is indispensable in the methodology, but may provide a certain restriction. The living polymer, which can react with 1, is essentially limited to highly reactive living

Polymers 2017, 9, 470 4 of 30 Polymers 2017, 9, 470 4 of 31 thepolystyrene arm and the (PSt),X functionality polyisoprene in (PIs), each poly(1,3-butadiene) sequence. Since the (PBd), final or (µ -SP)living still polymers has the derivedX functionality from convertibletheir related to the monomers.Y reaction Unfortunately, site, this procedure living enablespoly(2-vinylpyridine) further reaction (P2VPy) sequence. and Thus,poly(methyl the first proposedmethacrylate) iterative (PMMA) methodology with interesting works very functional satisfactorily groups ascannot designed. be used due to their very low or no reactivitiesThe DPE for derivative, the DPE functionality.1, is capable The of not use only of li reactingving P2VPy with and a living(PMMA) polymer in the linking but also reaction of offering is thepossibleX function. to introduce Thus, theP2VPy use or of (PMMA)1 is indispensable segment. In insuch the a methodology,case, however, butthe reaction may provide sequence a certain can restriction.no longer The be repeated living polymer, because whichthe X functionality can react with is not1, is introduced essentially in limited the linking to highly reaction. reactive living polystyreneVery (PSt),recently, polyisoprene a new and (PIs),improved poly(1,3-butadiene) methodology ha (PBd),s been orproposed, living polymers as illustrated derived in Scheme from their 2 related[49–52]. monomers. The key Unfortunately,of this methodology living poly(2-vinylpyridine) is to utilize two functionalities, (P2VPy) and X poly(methyl1 and X2, which methacrylate) can be (PMMA)deprotected with in interesting turn to separately functional convert groups to cannotthe first be and used second due toY reaction their very sites. low As or the no X reactivities1 and X2 forfunctionalities, the DPE functionality. trimethylsilyl The use(TMS) of livingand tert P2VPy-butyldimethylsilyl and (PMMA) (TBDMS) in the linking ethers reaction were selected. is possible As to introducethe starting P2VPy polymer, or (PMMA) a living segment. polymer In (A) such with a TMS case, and however, TBDMS the termini reaction was sequence prepared can by no the longer living be repeatedpolymerization because thewithX functionality the functional is not introducedanion obtained in the linking from reaction. sec-BuLi and 1-(3-tert- butyldimethylsilyloxymethylphenyl)-1-(3-trimethylsilyloxymethylphenyl)ethylene (2). The first Very recently, a new and improved methodology has been proposed, as illustrated in reaction sequence involves deprotection of the TMS group and the subsequent conversion of the Scheme2[ 49–52]. The key of this methodology is to utilize two functionalities, X1 and X2, regenerate OH group to an α-phenylacrylate (PA) reaction site, the reaction of a living polymer (B) which can be deprotected in turn to separately convert to the first and second Y reaction sites. with the reaction site, deprotection of the TBDMS group, followed by conversion to the reaction site, As the X and X functionalities, trimethylsilyl (TMS) and tert-butyldimethylsilyl (TBDMS) ethers and the1 reaction2 of the functional anion with the reaction site to reintroduce the TMS and TBDMS ethers. were selected. As the starting polymer, a living polymer (A) with TMS and TBDMS termini As was seen in Scheme 2, the TMS group was deprotected with MeOH containing K2CO3. The wasregenerated prepared byOH the group living was polymerization converted to the with PA the reaction functional site anionby the obtained Mitsunobu from reactionsec-BuLi with and 1-(3-α-phenylacrylictert-butyldimethylsilyloxymethylphenyl)-1-(3-trimethylsilyloxymethylphenyl)ethylene acid. The resulting (PA and TBDMS ether)-functionalized polymer was reacted ( 2with). The firsta living reaction polymer sequence (B) involvesto result deprotectionin an in-chain-(TBDMS of the TMS ether)-functionalized group and the subsequent AB diblock conversion copolymer. of the regenerateThe TBDMS OH group was to an thenα-phenylacrylate deprotected with (PA) (C reaction4H9)4NF, site, followed the reaction by conversion of a living to the polymer PA reaction (B) with thesite. reaction The functional site, deprotection anion, again of the obtained TBDMS from group, sec followed-BuLi and by 2,conversion reacted with to the reactionreaction site,site to and thereintroduce reaction of the the TMS functional and TBDMS anion ethers. with the reaction site to reintroduce the TMS and TBDMS ethers.

O-Si a = MeOH, K2CO3, a' = Bu4NF X1 Y O O C X2 i N OPri O-Si b = PPh3, PrO N O COOH 2 O

X1 X1 X1 X1 RLi Monomer MeOH -H R X2 X2 X2 X2

Y R X 1) a 1) a' X2 1 2) b 2) b X2 X2 Y X2

Y R 1) a 1) a' X2 X2 Y X1 2) b 2) b X X2 2

R 1) a 1) a' X2 Y X2 Y X1 X2 2) b 2) b X2

R X1 1) a 1) a' X2 Y X2 Y X2 X2 2) b 2) b

Scheme 2. (μ-SP) synthesis by the iterative methodology using X1 and X2 functionalities. Reproduced Scheme 2. (µ-SP) synthesis by the iterative methodology using X1 and X2 functionalities. Reproduced with permission from reference [49]. Copyright 2012 American Chemical Society. with permission from reference [49]. Copyright 2012 American Chemical Society.

Polymers 2017, 9, 470 5 of 30

As was seen in Scheme2, the TMS group was deprotected with MeOH containing K 2CO3. The regenerated OH group was converted to the PA reaction site by the Mitsunobu reaction with α-phenylacrylic acid. The resulting (PA and TBDMS ether)-functionalized polymer was reacted with a living polymer (B) to result in an in-chain-(TBDMS ether)-functionalized AB diblock copolymer. The TBDMS group was then deprotected with (C4H9)4NF, followed by conversion to the PA reaction site. The functional anion, again obtained from sec-BuLi and 2, reacted with the reaction site to reintroduce the TMS and TBDMS ethers. An ABC (µ-SP) with TMS and TBDMS ethers at the core was synthesized by iterating the second sequence. The reaction sequence was further continued to yield ABCD and ABCDE (µ-SP)s. Thus, the ﬁrst and second reaction sites are utilized for the arm introduction and the reintroduction of X1 and X2 functionalities convertible to the same reaction sites. The results are summarized in Table2. Agreement among the calculated Mn values, compositions and those observed was satisfactory and low polydispersity indexes were attained in all the resulting (µ-SP)s. Thus, the new methodology efﬁciently and expectedly operates to successively synthesize ABC, ABCD, and even ABCDE (µ-SP)s. The synthesis of (µ-SP)s with more compositions would be possible, since the two silyl ethers were introduced into the 5-arm (µ-SP).

Table 2. Characterization results of (µ-SP)s synthesized by the iterative methodology using X1 and X2 functionalities.

Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) Polymer Calcd. RALLS a SEC Calcd. 1H NMR 3-arm ABC 32.2 33.8 1.03 38/31/31 37/32/31 4-arm ABCD 43.4 43.0 1.03 30/25/22/23 36/26/20/24 5-arm ABCDE b 52.0 51.5 1.03 24/21/18/19/18 26/20/16/20/18 a Determined by SEC with RI, viscometer, and right angle laser light scattering (RALLS) detector. b A, B, C, D, and E arms correspond to (PMMA), poly(ethylmethacrylate), poly(tert-butylmethacrylate), poly(benzylmethacrylate), and poly(2-methoxyethylmethacrylate), respectively.

Unlike the first methodology, the advantage of this new methodology is that various living polymers, ranging from less reactive living (PMMA), P2VPy, to highly reactive living PSt, PIs, and PBd, are usable for the arm introduction because any of these living polymers readily reacts with the PA reaction site with the quantitative conversion of the reactive site. In fact, with this methodology, less reactive living (PMMA), poly(ethyl methacrylate), poly(tert-butyl methacrylate), poly(benzyl methacrylate), and poly(2-methoxyethyl methacrylate) all quantitatively reacted to afford a 5-arm all poly(methacrylate)-based ABCDE (µ-SP) for the first time. In the methodology, the BnBr functionality can also be used as the reaction site. However, as the conversion to the BnBr reaction site is usually carried out under strongly acidic conditions, some poly(alkyl methacrylate)s are not stable and pyridine ring in P2VPy might be formed to pyridinium salt under such conditions. The new iterative methodology was further extended to the methodology with three different protected functionalities, X1, X2, and X3, as illustrated in Scheme3[ 53]. The three functionalities are designed to be sequentially converted one order to the first, second, and third Y reaction sites at different steps. For this design, the TMS, TBDMS, and 2-tetrahydropyranyl (THP) ethers were chosen as the X1, X2, and X3 functionalities. The TMS group was first deprotected with MeOH containing K2CO3 and, on the other hand, the TBDMS and THP ethers remained unchanged. The TBDMS group was then deprotected with (C4H9)4NF under the conditions where the THP ether was stable. The THP ether was finally deprotected with 0.5 M HCl. The regenerated OH group in each step was converted to the PA reaction site one by one. Polymers 2017, 9, 470 6 of 30 Polymers 2017, 9, 470 6 of 31

O-Si a = MeOH, K2CO3

a' = Bu4NF O a" = 0.5N HCl O X1 3 Si-O-(CH2)3Li X2 O b = i X3 i N N OPr COOH, Ph3P, PrO Y: O O O

X1 X1 X1 Y X3 1) Monomer 1) a X2-Li X2 X2 X2 2) MeOH 2) b X3 X3 X3

X2 1) a' Y 1) a" X3 Y 2) b 2) b X3 X3

X2 X1 Y X3 1) a 1) a' X3 X3 X2 X3 Y X3 2) b 2) b X2 X2

X2 X1 Y 1) a" X3 1) a X3 Y X3 X3 2) b 2) b X2 X2

1) a' X3 X3 X3 X3 2) b X2 Y

X1 X3 X2

Scheme 3.3. ((μµ-SP)-SP) synthesis synthesis by by the iterativeiterative methodologymethodology usingusing XX11, X2,, and X3 functionalities. Reproduced with permission fromfrom referencereference [[5353].]. CopyrightCopyright 20132013 AmericanAmerican ChemicalChemical Society.Society.

TheAs summarized starting α-terminal in Table 3, (TMS,the Mn values TBDMS, observed and THP by RALLS ethers)-functionalized agreed well with calculated poly(cyclohexyl values methacrylate)and low polydispersity (PCHMA) indexes was prepared were attained by the livingin all polymerizationthe (μ-SP)s. Their of CHMAcompositions with thewere functional close to anioncalculated from values. 3-tert -butyldimethylsilyloxy-1-propyllithiumThus, the successful syntheses of expected and (μ-SP)s 1-(3-(2-tetrahydro-2 were evident fromH-pyranyloxy) the results methyl)phenyl-1-(3-trimethylsilyloxymethylphenyl)ethylenelisted in this table. Since the final ABCDEFG (μ-SP) still has ( 3the). TheTHP reaction functionality, sequence the involvesreaction severalsequence steps is possibly as follows: iterated. the TMS Thus, ether the deprotection third proposed and conversion methodology to the also PA works reaction well site, as the designed. linking withThe atwo living arms polymer, are introduced the TBDMS by ether the deprotectionfirst and second and conversionreaction sites to the and reaction the three site, theethers second are linkingreintroduced reaction by with the third another reaction living site polymer, to enable the THP further ether reaction deprotection sequence. and conversion to the reaction site, and the reaction with the functional anion to reintroduce the TMS, TBDMS, and THP ethers. By iterating such the reaction sequence, the successive synthesis from ABC, ABCD, ABCDE, ABCDEF and to even ABCDEFG (µ-SP)s were successfully achieved.

Polymers 2017, 9, 470 7 of 30

As summarized in Table3, the Mn values observed by RALLS agreed well with calculated values and low polydispersity indexes were attained in all the (µ-SP)s. Their compositions were close to calculated values. Thus, the successful syntheses of expected (µ-SP)s were evident from the results listed in this table. Since the ﬁnal ABCDEFG (µ-SP) still has the THP functionality, the reaction sequence is possibly iterated. Thus, the third proposed methodology also works well as designed. The two arms are introduced by the ﬁrst and second reaction sites and the three ethers are reintroduced by the third reaction site to enable further reaction sequence.

Table 3. Characterization results of (µ-SP)s synthesized by the iterative methodology using X1, X2, and X3 functionalities.

Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) Polymer Calcd. RALLS SEC Calcd. 1H NMR ABC 35.0 34.9 1.03 30/35/35 31/35/34 ABCD 45.9 47.1 1.03 23/26/27/25 24/25/27/24 ABCDE 56.6 53.5 1.04 20/21/22/20/17 20/23/21/20/16 ABCDEF 62.8 64.9 1.05 17/18/19/17/15/14 18/20/18/17/14/13 ABCDEFG a 73.8 74.2 1.04 14/16/17/15/13/13/12 16/17/16/14/12/12/13 a A, B, C, D, E, F, and G arms correspond to poly(cyclohexylmethacrylate), PSt, poly(4-methoxystyrene), poly(4-methylstyrene), (PMMA), poly(ethylmethacrylate), and poly(2-methoxyethylmethacrylate), respectively.

In this section, we proposed three iterative methodologies. In the ﬁrst methodology, the living end-X-functionalized polymer was used as the building block in each reaction sequence and the next sequence was continued after converting the X function to the Y reaction site. In the last two methodologies shown in Schemes2 and3, the functional anions were employed to reintroduce X1, X2 and X1, X2, X3 functionalities, with which their reaction sequences could be iterated. It should be mentioned, however, that these methodologies are basically designed in the same concept so that each reaction sequence involves two steps of the arm introduction and regeneration of the same reaction site and can be iterated to synthesize a series of multicomponent (µ-SP)s. As often mentioned, one more important advantage of such iterative methodologies is that, in essence, the use of multistep selective reactions and several reaction sites with different reactivities generally required for the (µ-SP) synthesis are completely avoided because one arm is introduced in each reaction step.

2.2. Dendrimer-Like Hyperbranched Polymers ((DHBH)s) A (DHBP) has emerged as the new class hyperbranched polymer with structural perfection since 1995 [54]. In order to clearly image the structure of (DHBP), the fifth-generation (5G) (DHBP) and its block copolymer are shown in Figure1. These polymers are similar in branched architecture to dendrimers, but comprise several polymers connected between the layers. Accordingly, (DHBP)s are much higher in molecular weight and much larger in molecular size than dendrimers. DHPBs, believed to be globular macromolecules in shape, have many features, such as topologically specific hyperbranched architectures, hierarchic repeated layer structures, so-called “generation”, different branched densities among the core and layers, and many termini [55–59]. Although various (DHBP)s have been synthesized to date, most of them were limited to 2G~4G 5 −1 polymers with Mn values of 10 g·mol order due to several reaction steps for the introduction of additional polymer chains [60–79]. As for high-generation (≥4G) and high-molecular-weight (≥106 g·mol−1) (DHBP)s with well-defined structures, there were reported only two examples 6 −1 synthesized by Gnanou et al. (7G DHB PSt with a Mn of 1.92 × 10 g·mol and 8G DHB poly(ethylene 5 −1 oxide) with a Mn of 6.50 × 10 g·mol ) and several (DHBP)s synthesized by Hirao et al. which will be described in this section [80–87]. As can be seen in Figure1, (DHBP)s comprise several repeating units on the basis of layer structures. It is, therefore, expected that the iterative methodology is applicable to the synthesis of (DHBP)s, as illustrated in Scheme4[ 82,83]. In the first reaction sequence, a living α-chain- Polymers 2017, 9, 470 7 of 31

Table 3. Characterization results of (μ-SP)s synthesized by the iterative methodology using X1, X2,

and X3 functionalities.

In this section, we proposed three iterative methodologies. In the first methodology, the living end-X-functionalized polymer was used as the building block in each reaction sequence and the next sequence was continued after converting the X function to the Y reaction site. In the last two methodologies shown in Schemes 2 and 3, the functional anions were employed to reintroduce X1, X2 and X1, X2, X3 functionalities, with which their reaction sequences could be iterated. It should be mentioned, however, that these methodologies are basically designed in the same concept so that each reaction sequence involves two steps of the arm introduction and regeneration of the same Polymersreaction2017 site, 9, 470and can be iterated to synthesize a series of multicomponent (μ-SP)s. As 8often of 30 mentioned, one more important advantage of such iterative methodologies is that, in essence, the use of multistep selective reactions and several reaction sites with different reactivities generally required end-(for theX )(2μ-functionalized-SP) synthesis are polymer completely reacted avoided with because a core havingone arm four is introducedY reaction in siteseach toreaction result step. in a 4-arm (SP). The introduced eight X termini were then converted to the Y reaction sites. In the second2.2. Dendrimer-Like sequence, the Hyperbranched resulting (SP) Polymers with ( Y((DHBH)s))8 termini was linked with a separately prepared living α-chain-end-(X)2-functionalized polymer to yield a 2G (DHBP) with sixteen X termini. Thus, the A (DHBP) has emerged as the new class hyperbranched polymer with structural perfection since living α-chain-end-(X)2-functionalized polymer is used as the building block in each reaction sequence. As1995 was [54]. seen, In order the (DHBP) to clearly was image obtained the structure from the of second (DHBP), sequence. the fifth-generation The linking of (5G) the (DHBP) living polymer and its block copolymer are shown in Figure 1. These polymers are similar in branched architecture to with either the core compound or the polymer with (Y)8 termini and the conversion to the Y reaction sitedendrimers, are exactly but equal comprise to (1) several the arm polymers introduction connect anded (2) between regeneration the layers. of the Accordingly, reaction site, (DHBP)s respectively. are SincemuchPolymers thehigher 2G 2017 (DHBP)in, 9 , molecular470 possesses weight the and sixteen muchY reaction larger in sites, molecular the reaction size than sequence dendrimers. can be8 repeated. ofDHPBs, 31 Indeed,believed it to was be repeatedglobular tomacromolecules successively synthesize in shape, 3G, ha 4G,ve many 5G, 6G, features, and even such 7G as (DHBP)s topologically (see Scheme specific5). additional polymer chains [60–79]. As for high-generation (≥4G) and high-molecular-weight Ashyperbranched can be seen, thearchitectures, polymer obtained hierarchic in one repeated reaction layer sequence structures, before so-called becomes “generation”, the starting polymer different in (≥106 g·mol−1) (DHBP)s with well-defined structures, there were reported only two examples thebranched next sequence densities [ 83among]. the core and layers, and many termini [55–59]. synthesized by Gnanou et al. (7G DHB PSt with a Mn of 1.92 × 106 g·mol−1 and 8G DHB poly(ethylene oxide) with a Mn of 6.50 × 105 g·mol−1) and several (DHBP)s synthesized by Hirao et al. which will be

described in this section [80–87]. As can be seen in Figure 1, (DHBP)s comprise several repeating units on the basis of layer structures. It is, therefore, expected that the iterative methodology is applicable to the synthesis of (DHBP)s, as illustrated in Scheme 4 [82,83]. In the first reaction sequence, a living α-chain-end-(X)2- functionalized polymer reacted with a core having four Y reaction sites to result in a 4-arm (SP). The introduced eight X termini were then converted to the Y reaction sites. In the second sequence, the resulting (SP) with (Y)8 termini was linked with a separately prepared living α-chain-end-(X)2- functionalized polymer to yield a 2G (DHBP) with sixteen X termini. Thus, the living α-chain-end- (X)2-functionalized polymer is used as the building block in each reaction sequence. As was seen, the (DHBP) was obtained from the second sequence. The linking of the living polymer with either the core compound or the polymer with (Y)8 termini and the conversion to the Y reaction site are exactly equal to (1) the arm introduction and (2) regeneration of the reaction site, respectively. Since the 2G (DHBP) possesses the sixteen Y reaction sites, the reaction sequence can be repeated. Indeed, it was repeated to successively synthesize 3G, 4G, 5G, 6G, and even 7G (DHBP)s (see Scheme 5). As can be seen, the polymer obtained in one reaction sequence before becomes the starting polymer in the next Figure 1. 5G (DHBP) and its block copolymer. sequence [83]. Figure 1. 5G (DHBP) and its block copolymer.

Although various (DHBP)s have been synthesized to date, most of them were limited to 2G~4 G polymers with Mn values of 105 g·mol−1 order due to several reaction steps for the introduction of

SchemeScheme 4. Synthesis4. Synthesis of of 1G 1G and and 2G2G polymers by by the the iterative iterative methodology. methodology.

The building block was prepared by the living polymerization of MMA with the initiator obtained from sec-BuLi and 1,1-bis(3-tert-butyldimethylsilyloxymethylphenyl)ethylene (4). Similar to the previous methodologies, the introduced TBDMS ether (X) is readily and quantitatively converted to the BnBr (Y) reaction site. The linking reactions proceeded with ~100% efficiencies at −40 °C for a few hours with 2 equivalents of living α-chain-end-(TBDMS)2-functinalized (PMMA) to afford 2G,

Polymers 2017, 9, 470 9 of 31

3G, and 4G polymers. The use of 3–5 equivalents of living (PMMA) and longer reaction times to 48 h Polymers 2017, 9, 470 9 of 30 were needed to complete the reaction, yielding 5G, 6G, and 7G polymers.

SchemeScheme 5. Successive synthesis of DHB (PMMA)s (1G–7G) by the iterative methodology. Reproduced withwith permissionpermission fromfrom referencereference [[83].83]. CopyrightCopyright 20052005 AmericanAmerican ChemicalChemical Society.Society.

TheAs summarized building block in was Table prepared 4, the result by theing living DHB polymerization (PMMA)s all of had MMA well-controlled with the initiator Mn values obtained in fromagreementsec-BuLi with and those 1,1-bis(3- calculatedtert -butyldimethylsilyloxymethylphenyl)ethyleneand low polydispersity indexes, (Mw/Mn ≤ 1.03). Agreement (4). Similar between to the previousthe calculated methodologies, values andthe those introduced observed TBDMS in end-func ethertionality (X) is readily is excellent and quantitatively in each of all samples. converted The to the7G BnBrDHB ((PMMA)Y) reaction was site. a huge The linking macromolecule reactions with proceeded a Mw value with ~100% of 1.97 efficiencies × 106 g mol at−1 −and40 ◦consistedC for a few of hours508 (PMMA) with 2 equivalents segments having of living 512α-chain-end-(TBDMS) BnBr termini, which2-functinalized enable further (PMMA) synthetic to affordsequence 2G, of 3G, more and 4Ggeneration polymers. (DHBP)s. The use Thus, of 3–5 the equivalents synthesis of of well-d livingefined (PMMA) (DHBP)s and longerwas quite reaction successful times by to employing 48 h were neededthe iterative to complete methodology the reaction, using yieldingthe living 5G, α-chain-end-(TBDMS 6G, and 7G polymers. ether)2-functionalized polymer as the buildingAs summarized block. This in Table success4, the also resulting made DHBit poss (PMMA)sible to synthesize all had well-controlled other (DHBP)sM maden values up inof t agreementpoly(tert-butyl with thosemethacrylate) calculated (P andBMA), low polydispersityPSt, and a mixture indexes, of (M thesew/M ntwo≤ 1.03). polymers Agreement by a betweenslightly themodified calculated procedure values andusing those the observed PA reaction in end-functionality site. Several isamphiphilic excellent in eachgeneration-based of all samples. block The 6 −1 7Gcopolymers DHB (PMMA) with PSt was and a huge poly(methacrylic macromolecule acid) with alayersMw value could of be 1.97 obtained× 10 g ·frommol theand DHB consisted block ofcopolymers 508 (PMMA) consisting segments of (P havingtBMA) 512 and BnBr PSt, termini,followed which by hydrolysis enable further of the synthetic(PtBMA) sequencesegments of[86]. more generation (DHBP)s. Thus, the synthesis of well-defined (DHBP)s was quite successful by employing Table 4. Characterization results of the DHB (PMMA)s (1G–7G). the iterative methodology using the living α-chain-end-(TBDMS ether)2-functionalized polymer as the building block.M Thisn (kg/mol) success also madeMw (kg/mol) it possible to synthesizeMw/Mn otherEnd-Functionality (DHBP)s made up of Polymer poly(tert-butyl methacrylate)Calcd. 1H (P NMRtBMA), PSt, Calcd. and a mixture SLS a of theseSEC two polymers Calcd. by a slightly1H NMR modified procedure1G using the 14.6 PA reaction14.2 site. Several14.9 amphiphilic14.8 generation-based 1.02 block 8 copolymers 7.90 with PSt and poly(methacrylic2G 43.0 acid) layers42.9 could43.9 be obtained44.2 from the DHB 1.02 block copolymers 16 consisting 16.0 of (PtBMA)3G and PSt, followed97.3 by98.4 hydrolysis 99.2 of the (PtBMA)105 segments 1.02 [86]. 32 32.6 A highly4G dense219 3G DHB219 (PMMA) with223 four polymer230 chains 1.02 branched at 64 the core as 64. well0 as in 5G 452 449 462 472 1.03 128 127 the two layers was synthesized by the iterative methodology with a living α-chain-end-(TBDMS 6G 980 974 1000 1060 1.02 256 254 ether) -functionalized (PMMA) (see Scheme6)[ 84]. The resulting polymer had a M value of 4 7G 1950 1940 1980 1970 1.02 512 509n 9.30 × 105 g·mol−1 and 256 BnBr termini (see Table5). Further synthesis was not possible in this a static light scattering (SLS). Arm segments are adusted to be in the range of 3500~4000 g·mol−1 in Mn value. case. Instead, three different 4G (DHBP)s shown in Figure2 could be synthesized by using the living α-chain-end-(TBDMS)2-functionalized (PMMA) in either the second, third, or fourth reaction sequence.

Polymers 2017, 9, 470 10 of 30

All of the polymers were around 2 million in Mn value with 512 BnBr termini even in the 4G polymers (see also Table5)[85].

Table 4. Characterization results of the DHB (PMMA)s (1G–7G).

M (kg/mol) M (kg/mol) M /M End-Functionality Polymer n w w n Calcd. 1H NMR Calcd. SLS a SEC Calcd. 1H NMR Polymers 2017, 9, 470 10 of 31 1G 14.6 14.2 14.9 14.8 1.02 8 7.90 2GA highly 43.0 dense 3G DHB 42.9 (PMMA) with 43.9 four polymer 44.2 chains branched 1.02 at the core 16 as well as in 16.0 3Gthe two layers 97.3 was synthesized 98.4 by the 99.2iterative methodology 105 with a 1.02 living α-chain-end-(TBDMS 32 32.6 4G 219 219 223 230 1.02 64 64.0 ether)4-functionalized (PMMA) (see Scheme 6) [84]. The resulting polymer had a Mn value of 9.30 × 5G 452 449 462 472 1.03 128 127 105 g·mol−1 and 256 BnBr termini (see Table 5). Further synthesis was not possible in this case. Instead, 6G 980 974 1000 1060 1.02 256 254 three different 4G (DHBP)s shown in Figure 2 could be synthesized by using the living α-chain-end- 7G 1950 1940 1980 1970 1.02 512 509 (TBDMS)2-functionalized (PMMA) in either the second, third, or fourth reaction sequence. All of the a · −1 staticpolymers light scatteringwere around (SLS). 2 million Arm segments in Mn value are adusted with 512 to BnBr be in thetermini range even of 3500~4000 in the 4G g polymersmol in M(seen value. also Table 5) [85].

Scheme 6. Successive synthesis of highly dense DHB (PMMA)s (1G–3G). Reproduced with Scheme 6. Successive synthesis of highly dense DHB (PMMA)s (1G–3G). Reproduced with permission permission from ref [84]. Copyright 2006 WILLEY-VCH Veriag GmbH & Co. KGaA, Weinheim, from ref.Germany. [84]. Copyright 2006 WILLEY-VCH Veriag GmbH & Co. KGaA, Weinheim, Germany.

TableTable 5. Characterization 5. Characterization results results of of highlyhighly dense dense DHB DHB (PMMA)s (PMMA)s (1G–4G). (1G–4G).

Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) Polymer 1Mn (kg/mol) Mw/Mn Composition1 (wt % wt % wt %) Polymer Calcd. H NMR SLS SEC Calcd. H NMR 1G Calcd.52.8 152.2H NMR 51.6 SLS1.02 SEC 16 Calcd. 16.1 1H NMR 1G2G 52.8236 234 52.2 247 51.61.02 1.02 64 16 63.6 16.1 2G3G 236938 959 234 930 2471.01 1.02 256 64 259 63.6 3G4G-1 9382350 2330 959 2330 9301.02 1.01 512 256 521 259 4G-14G-2 23501860 1900 2330 1860 23301.03 1.02 512 512 528 521 4G-24G-3 18601910 1930 1900 1880 18601.02 1.03 512 512 516 528

4G-3 1910PMMA arm segments 1930 are adjusted 1880 to be ca. 10,000 1.02 g·mol−1 in Mn 512 value. 516 −1 PMMA arm segments are adjusted to be ca. 10,000 g·mol in Mn value.

Polymers 2017, 9, 470 11 of 30

Polymers 2017, 9, 470 11 of 31

Figure 2. SEC Profiles of 4G-1, 4G-2, and 4G-3 DHB (PMMA)s. Reproduced with permission from Figure 2. SEC Profiles of 4G-1, 4G-2, and 4G-3 DHB (PMMA)s. Reproduced with permission from reference [85]. Copyright 2009 American Chemical Society. reference [85]. Copyright 2009 American Chemical Society. We demonstrated the effectiveness of the iterative methodology for the synthesis of high- generationWe demonstrated and high-molecular-weight the effectiveness (DHBP)s. of the The iterative methodologies methodology shown forin Schemes the synthesis 4–6 are of high-generationbasically the same and high-molecular-weightas that shown in Scheme (DHBP)s.1, except for The the methodologies use of different shown building in blocks Schemes and4– the6 are basicallycore compound. the same asSince that highly shown reactive in Scheme BnBr1 ,or except PA termini for the are use present of different in the buildingintermediate blocks and and final the corepolymers, compound. various Since useful highly functionalities, reactive BnBr such or as PA perfluoroalkanes, termini are present olefins in (double the intermediate bonds), acetylenes and final polymers,(triple bonds), various alkoxy useful and functionalities, hydrosilanes, such epoxide, as perfluoroalkanes, thiol, phosphine, olefins ferrocene, (double and bonds),monosaccharide acetylenes (tripleresidues, bonds), etc., alkoxy can be and introduced hydrosilanes, at any generation, epoxide, thiol, internal, phosphine, and external ferrocene, positions and [55]. monosaccharide As a result, residues,well-defined etc., can functional be introduced hyperbranched at any generation,and nano-size internal, globular and macromolecules external positions with many [55]. Aspotential a result, well-definedapplications functional are synthesized. hyperbranched Novel and and interestin nano-sizeg morphological globular macromolecules nanostructures and with supramolecular many potential assemblies will also be expected from generation-based DHB block polymers [55,56,58,76,77,79]. applications are synthesized. Novel and interesting morphological nanostructures and supramolecular assemblies will also be expected from generation-based DHB block polymers [55,56,58,76,77,79]. 2.3. Graft Polymers ((GP)s) 2.3. GraftAs Polymers illustrated ((GP)s) in Figure 3, a (GP) is defined by three structural parameters: (1) molecular weight of the main chain; (2) molecular weight of the graft chain; and (3) distance between the graft chains. As illustrated in Figure3, a (GP) is defined by three structural parameters: (1) molecular weight An ideal (GP), in which the three parameters are perfectly controlled, is termed an “exactly defined of the main chain; (2) molecular weight of the graft chain; and (3) distance between the graft chains. graft polymer (EDGP)” [88]. Although the physical and mechanical properties as well as morphology Anof ideal (GP) (GP), are significantly in which the influenced three parameters by such three are perfectlystructural controlled, parameters, is their termed relationships an “exactly have defined not graftbeen polymer enough (EDGP)” elucidated [88 ].due Although to the synthetic the physical difficul andty mechanical of (EDGP) properties[1,2,89–91]. as In well practice, as morphology various of (GP)(GP)s are have significantly been synthesized influenced so far, by suchbut all three of them structural are not parameters, (EDGP)s, except their relationshipsfor the PIs–graft have–PSt not beenreported enough by elucidated Hadjichristidis due to et the al. synthetic[88] and several difficulty graft of (EDGP)polymers [1 synthesize,2,89–91].d In by practice, Hirao et various al., which (GP)s havewill been be introduced synthesized in sothis far, section but all[92–97]. of them are not (EDGP)s, except for the PIs–graft–PSt reported by HadjichristidisAs shown in et Scheme al. [88 ]7, and a living several PIs reacted graft polymers with 1,4-bis(phenylethenyl)benzene synthesized by Hirao et al.,(5) to which introduce will be introduceda DPE terminus. in this section After the [92 termination,–97]. a living PSt reacted with the DPE terminus to prepare a PIs– blockAs–PSt shown in-chain in Scheme anion,7, afrom living which PIs reactedisoprene with was 1,4-bis(phenylethenyl)benzene polymerized. The resulting living ( 5 )3-arm to introduce (SP) a DPEreacted terminus. with 5 to After again the introduce termination, the DPE a living terminus. PSt reactedThe same with reaction the DPE sequence terminus was toiterated prepare to a PIs–synthesizeblock–PSt in-chaina PIs–graft anion,–PSt with from two which PSt isoprenegraft chains. was In polymerized. the resulting Thepolymer, resulting the three living structural 3-arm (SP) reactedparameters with 5 areto perfectly again introduce controlled the by DPE the living terminus. polymerization The same of reactioneither isop sequencerene or styrene was iterated in each to synthesizestep. Although a PIs–graft the synthesis–PSt with of two(EDGP)s PSt graftwith more chains. than In three the resultinggraft chains polymer, is possible the by three iterating structural the reaction sequence, it seems difficult because an exact stoichiometry is required in each reaction parameters are perfectly controlled by the living polymerization of either isoprene or styrene in each between living PSt and the DPE terminus. If the stoichiometry is deviated in the reaction, many side step. Although the synthesis of (EDGP)s with more than three graft chains is possible by iterating the products difficult in separation are by-produced. Later, an (EDGP) having five graft chains was reaction sequence, it seems difficult because an exact stoichiometry is required in each reaction between successfully synthesized by an improved methodology based on the termination procedure [92]. living PSt and the DPE terminus. If the stoichiometry is deviated in the reaction, many side products Polymers 2017, 9, 470 12 of 30 difficult in separation are by-produced. Later, an (EDGP) having five graft chains was successfully synthesizedPolymers by 2017 an, 9,improved 470 methodology based on the termination procedure [92]. 12 of 31 Polymers 2017, 9, 470 12 of 31

FigureFigure 3. Three 3. Three structural structural parameters parameters to to deﬁne define graftgraft polymer. Repr Reproducedoduced with with permission permission from from Figure 3. Three structural parameters to define graft polymer. Reproduced with permission from reference [88]. Copyright 2006 WILLEY-VCH Veriag GmbH & Co. KGaA, Weinheim, Germany. referencereference [88]. Copyright[88]. Copyright 2006 2006 WILLEY-VCH WILLEY-VCH VeriagVeriag GmbH GmbH & & Co. Co. KGaA, KGaA, Weinheim, Weinheim, Germany. Germany.

Scheme 7. Synthesis of (EDGP) with two PSt graft chains. Reproduced with permission from reference Scheme 7. Synthesis of (EDGP) with two PSt graft chains. Reproduced with permission from reference Scheme[92]. 7. CopyrightSynthesis 2009 of American (EDGP) Chemical with two Society. PSt graft chains. Reproduced with permission from [92]. Copyright 2009 American Chemical Society. reference [92]. Copyright 2009 American Chemical Society. It is considered that the iterative methodologies are applicable because (EDGP)s comprise It is considered that the iterative methodologies are applicable because (EDGP)s comprise several repeating units linked each other. As can be seen in Figure 4, one building unit of graft several repeating units linked each other. As can be seen in Figure 4, one building unit of graft It ispolymer considered corresponds that the to an iterative AB diblock methodologies copolymer and are the applicable two block becausecopolymers (EDGP)s are linked comprise between several polymer corresponds to an AB diblock copolymer and the two block copolymers are linked between repeatingthe unitschain-end linked and eachin-chain other. of diblock As can copolymers be seen to in make Figure the 4graft, one unit. building Therefore, unit if the of linking graft polymer of the chain-end and in-chain of diblock copolymers to make the graft unit. Therefore, if the linking of correspondsdiblock to copolymers an AB diblock can be copolymer iterated, a andseries the of twoexactly block defined copolymers graft copolymers are linked would between be the diblock copolymers can be iterated, a series of exactly defined graft copolymers would be chain-endsynthesized. and in-chain of diblock copolymers to make the graft unit. Therefore, if the linking of synthesized. diblock copolymersOn the basis can of bethe iterated, linking manner a series indicated of exactly in Fi deﬁnedgure 4, we graft proposed copolymers the iterative would methodology be synthesized. as illustratedOn the basis in Scheme of the linking 8 [93,94]. manner This methodologyindicated in Fi isgure basically 4, we proposedthe same asth ethose iterative shown methodology in Schemes On the basis of the linking manner indicated in Figure4, we proposed the iterative methodology as1 andillustrated 4–6, except in Scheme for the 8 use [93,94]. of the This living methodology in-chain-X-functionalized is basically the diblocksame as copolymer those shown as thein Schemes building 1 and 4–6, except for the use of the living in-chain-X-functionalized diblock copolymer as the building as illustratedblock. It inwas Scheme prepared8[ by 93the,94 sequential]. This addition methodology of styrene, is 1 basically, and MMAthe and, same after the as termination, those shown in block. It was prepared by the sequential addition of styrene, 1, and MMA and, after the termination, Schemes 1 and4–6, except for the use of the living in-chain- X-functionalized diblock copolymer as the building block. It was prepared by the sequential addition of styrene, 1, and MMA and, after the termination, the TBDMS ether was converted to the BnBr reaction site. Another Polymers 2017, 9, 470 13 of 30

Polymers 2017, 9, 470 13 of 31 living in-chain-TBDMS ether-functionalized PSt–block–PMMA was reacted with the resulting PA-functionalizedthe TBDMS PSt– etherblock was–PMMA converted toto the link BnBr the reaction two block site. Another copolymers living in-chain-TBDMS between the ether- chain-end and the in-chain.functionalized Since the PSt– TBDMSblock–PMMA ether was was reacted also with introduced, the resulting repetition PA-functionalized of the PSt– sameblock reaction–PMMA sequence to link the two block copolymers between the chain-end and the in-chain. Since the TBDMS ether was is possible.also In practice,introduced, the repetition reaction of the sequence same reaction was iteratedsequence fouris possible. more In times. practice, The the ﬁnal reaction polymer with ﬁve graft chainssequence was was yielded iterated byfour linking more times. the intermediateThe final polymer graft with copolymer five graft chains with was a livingyielded(PMMA). by The requisite structureslinking the ofintermediate the synthesized graft copolymer graft copolymerswith a living (PMMA). all were The clearly requisite evidenced structures fromof the the results summarizedsynthesized in Table 6graft. Thus, copolymers the proposed all were clearly methodology evidenced from satisfactorily the results summarized worked as in expected. Table 6. Thus, the proposed methodology satisfactorily worked as expected.

Figure 4. Synthesis of (EDGP) by the linking reaction between two AB diblock copolymers. PolymersFigure 2017 4., Synthesis9, 470 of (EDGP) by the linking reaction between two AB diblock copolymers.14 of 31 Table 6. Characterization results of exactly defined (PMMA–graft–PSt)s synthesized by the iterative methodology.

Composition Mn (kg/mol) Mw/Mn Polymer (wt % wt % wt %) a) Calcd. 1H NMR RALLS SEC Calcd. 1H NMR AB Diblock 12.5 12.6 12.6 1.03 50/50 48/52 EG-2 b) 22.2 22.5 23.6 1.02 51/49 50/50 EG-3 c) 33.8 35.4 34.6 1.04 50/50 49/51 EG-4 d) 43.5 46.1 45.6 1.04 49/51 50/50 EG-5 e) 56.2 56.0 55.0 1.02 45/55 45/55 a) PS/PMMA.

Scheme 8. Successive synthesis of exactly defined (PMMA–graft–PSt)s by the iterative methodology. Scheme 8. Successive synthesis of exactly deﬁned (PMMA–graft–PSt)s by the iterative methodology. Reproduced with permission from reference [93]. Copyright 2009 American Chemical Society. Reproduced with permission from reference [93]. Copyright 2009 American Chemical Society. Each reaction sequence involves the linking reaction between two block copolymers and the conversion to the reaction site, which are equal to the “polymer chain introduction” and “regeneration of the same reaction site” and can be iterated via the regenerated same reaction site. The three parameters of the resulting polymers are controlled and can be intentionally changed by the living first and second blocks. With this in mind, three additional acid-labile segment containing exactly defined PtBMA–graft–PSt, poly(ferrocenylmethyl methacrylate (PFMMA))–graft–PSt, and P2VPy–graft–PSt were also synthesized by the same iterative methodology using a PA reaction site. All of these polymers thus synthesized by the iterative methodology are the first successful (EDGP)s with more than three graft chains. Recently, we have succeeded in the synthesis of an EDG terpolymer with two different graft chains per one graft point by the iterative methodology using a living in-chain-(X1 and X2)- functionalized diblock copolymer (see Scheme 9) [97]. Both the X1 and X2 functionalities are designed so as to be converted in turn to the first and second Y reaction sites in different reaction steps. The first graft chain corresponding to the first PSt block was already present. The second graft chain was introduced by linking a living polymer at the first Y reaction site converted from the X1 function. Next, a newly prepared living in-chain-(X1 and X2)-functionalized block copolymer reacted with the second Y reaction site from the X2 function. As the X1 and X2 functionalities were thus reintroduced, the same reaction sequence was iterated to continue the synthesis of EDG terpolymers.

Polymers 2017, 9, 470 13 of 31

the TBDMS ether was converted to the BnBr reaction site. Another living in-chain-TBDMS ether- functionalized PSt–block–PMMA was reacted with the resulting PA-functionalized PSt–block–PMMA to link the two block copolymers between the chain-end and the in-chain. Since the TBDMS ether was also introduced, repetition of the same reaction sequence is possible. In practice, the reaction sequence was iterated four more times. The final polymer with five graft chains was yielded by linking the intermediate graft copolymer with a living (PMMA). The requisite structures of the synthesized graft copolymers all were clearly evidenced from the results summarized in Table 6. Thus, the proposed methodology satisfactorily worked as expected.

Polymers 2017, 9, 470 14 of 30

Table 6. CharacterizationFigure 4. Synthesis of results(EDGP) by of the exactly linking deﬁnedreaction between (PMMA– two graftAB diblock–PSt)s copolymers. synthesized by the iterative methodology. Table 6. Characterization results of exactly defined (PMMA–graft–PSt)s synthesized by the iterative

methodology. a) Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) Polymer 1 Composition 1 Calcd. H NMRMn (kg/mol)RALLS SECMw/Mn Calcd. H NMR Polymer (wt % wt % wt %) a) AB Diblock 12.5Calcd. 12.61H NMR 12.6 RALLS 1.03 SEC 50/50Calcd. 1H NMR 48/52 b) EG-2AB Diblock 22.2 12.5 22.5 12.6 23.6 12.6 1.02 1.03 51/49 50/50 48/52 50/50 c) EG-3 EG-2 b) 33.822.2 35.4 22.5 34.6 23.6 1.04 1.02 50/50 51/49 50/50 49/51 d) EG-4 EG-3 c) 43.533.8 46.1 35.4 45.6 34.6 1.04 1.04 49/51 50/50 49/51 50/50 e) EG-5 EG-4 d) 56.243.5 56.0 46.1 55.0 45.6 1.02 1.04 45/55 49/51 50/50 45/55 EG-5 e) 56.2 56.0 a) PS/PMMA. 55.0 1.02 45/55 45/55 a) PS/PMMA.

Each reaction sequence involves the linking reaction between two block copolymers and the conversion to the reaction site, which are equal to the “polymer chain introduction” and “regeneration of the same reaction site” and can be iterated via the regenerated same reaction site. The three parameters of the resulting polymers are controlled and can be intentionally changed by the living first and second blocks. With this in mind, three additional acid-labile segment containing exactly defined PtBMA–graft–PSt, poly(ferrocenylmethyl methacrylate (PFMMA))–graft–PSt, and P2VPy–graft–PSt were also synthesized by the same iterative methodology using a PA reaction site. All of these polymers thus synthesized by the iterative methodology are the first successful (EDGP)s with more than three graft chains. Recently, we have succeeded in the synthesis of an EDG terpolymer with two different graft chains per one graft point by the iterative methodology using a living in-chain-(X1 and X2)-functionalized diblock copolymer (see Scheme9)[ 97]. Both the X1 and X2 functionalities are designed so as to be converted in turn to the first and second Y reaction sites in different reaction steps. The first graft chain corresponding to the first PSt block was already present. The second graft chain was introduced by linking a living polymer at the first Y reaction site converted from the X1 function. Next, a newly prepared living in-chain-(X1 and X2)-functionalized block copolymer reacted with the second Y reaction site from the X2 function. As the X1 and X2 functionalities were thus reintroduced, the same reaction sequence was iterated to continue the synthesis of EDG terpolymers. As mentioned before, the TMS and TBDMS ethers are used as the X1 and X2 functionalities, respectively. In the first reaction sequence, a living in-chain-(TMS and TBDMS ethers)-functionalized PSt–block–PMMA was prepared by the sequential polymerization of styrene, 2, and MMA. The introduced TMS group in-chain was deprotected with MeOH containing K2CO3 and the regenerated OH group was converted to the PA reaction site. The second graft chain was introduced by linking with a living poly(2-methoxyethyl methacrylate) (P2MEMA). The TBDMS group was then deprotected with (C4H9)4NF, followed by converting to the reaction site. A living in-chain-(TMS and TBDMS ethers)-functionalized PSt–block–PMMA was newly prepared and reacted with the resulting PA-functionalized 3-arm (µ-SP) composed of PSt, (PMMA), and P2MEMA. By this linking reaction, one branched unit was made and the TMS and TBDMS ethers were also reintroduced. Repetition of the reaction sequence is possible via the two silyl ethers. An EDG terpolymer possessing three branched units was yielded after iterating the reaction sequence two more times, followed by linking with a living (PMMA) in the final step. Since all of the repeating reaction sequences proceeded almost quantitatively, the target polymers were always obtained in ca. 100% yields. Polymers 2017, 9, 470 15 of 30

The polymers all were obtained with well-controlled Mn values and compositions (see Table7). Accordingly, the proposed methodology also effectively worked to successfully yield the target EDG terpolymers. The three structural parameters of such graft terpolymers are also controlled and intentionallyPolymers 2017, changed9, 470 by the living polymerization in each step. 15 of 31

SchemeScheme 9. 9.Successive Successive synthesis synthesis ofof EDGEDG terpolymersterpolymers by by the the iterative iterative methodology methodology with with the the use use of of livingliving in-chain-( in-chain-(X1Xand1 andX X2)-functionalized2)-functionalized diblock copolymer. copolymer. Re Reproducedproduced from from Reference Reference [97] [97 with] with permissionpermission from from the the CentreCentre NationalNational de de la la Recher Rechercheche Scientifique Scientiﬁque (CNRS) (CNRS) and and The TheRoyal Royal Society Society of ofChemistry.

As mentioned before, the TMS and TBDMS ethers are used as the X1 and X2 functionalities, With the iterative methodology shown in Scheme8, both graft and main chains are advantageously respectively. In the first reaction sequence, a living in-chain-(TMS and TBDMS ethers)-functionalized introduced at the same time. We have recently developed an alternative methodology using a living PSt–block–PMMA was prepared by the sequential polymerization of styrene, 2, and MMA. The α-chain-end-(X1 and X2)-functionalized polymer (see Scheme 10)[96]. The same as Scheme9, the introduced TMS group in-chain was deprotected with MeOH containing K2CO3 and the regenerated X and X functionalities are TMS and TBDMS ethers and sequentially deprotected one by one to 1OH group2 was converted to the PA reaction site. The second graft chain was introduced by linking convertwith a to living the ﬁrst poly(2-methoxyethyl and second PA (Y) reactionmethacry sites.late) (P2MEMA). The synthesis The was TBDMS started group to prepare was athen living α-chain-end-(TMS and TBDMS ethers)-functionalized poly(benzyl methacrylate) (PBnMA) by the deprotected with (C4H9)4NF, followed by converting to the reaction site. A living in-chain-(TMS and livingTBDMS polymerization ethers)-functionalized of BnMA PSt– withblock the–PMMA functional was newly initiator prepared obtained and from reactedsec with-BuLi the and resulting2. After thePA-functionalized termination and 3-arm the conversion (μ-SP) composed of the TMSof PSt, ether (PMMA), to the and reaction P2MEMA. site, aBy living this linking (PMMA) reaction, reacted withone the branched reaction unit site was to resultmade and in an the in-chain-TBDMS TMS and TBDMS ether-functionalized ethers were also reintroduced. (PMMA)– Repetitionblock–PBnMA. of Thethe TBDMS reaction ethersequence was is thenpossible converted via the totwo the silyl reaction ethers. An site. EDG The terpolymer in-chain-PA-functionalized possessing three (PMMA)–branchedblock units–PBnMA was yielded thus after prepared iterating was the linked reaction with sequence a newly two prepared more times, living followedα-chain-end-(TMS by linking andwith TBDMS a living ethers)-functionalized (PMMA) in the final step. PBnMA. Since all By of this the reaction,repeating onereaction branched sequences unit proceeded was made almost and the quantitatively, the target polymers were always obtained in ca. 100% yields. The polymers all were obtained with well-controlled Mn values and compositions (see Table 7). Accordingly, the proposed methodology also effectively worked to successfully yield the target EDG

Polymers 2017, 9, 470 16 of 30

TMS and TBDMS ethers were reintroduced. The reaction sequence was iterated twice. In each of the intermediate polymers thus obtained, the TBDMS ether was converted to the reaction site, followed by linking with a living PBnMA, to synthesize the exactly deﬁned PBnMA–graft–PMMA with two and Polymers 2017, 9, 470 16 of 31 three (PMMA) graft chains. terpolymers. The three structural parameters of such graft terpolymers are also controlled and intentionallyTable 7. Characterization changed by the results living ofpolymerization EDG terpolymers in each synthesized step. by the iterative methodology.

a) Table 7. CharacterizationMn results(kg/mol) of EDG terpolymersM synthesizedw/Mn byComposition the iterative methodology. (wt % wt % wt %) Polymer Calcd. RALLS SEC Calcd. 1H NMR Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) a) Polymer AB Diblock 20.9Calcd. RALLS 21.0 SEC 1.03 Calcd. 48/52/01H NMR 48/52/0 0 EGTP-1ABb) Diblock 29.1 20.9 21.0 30.2 1.03 1.02 48/52/0 35/37/28 48/52/0 34/38/28 0 c) EGTP-2EGTP-1′ b) 61.729.1 30.2 61.5 1.02 1.04 35/37/28 34/35/31 34/38/28 32/38/30 0 d) EGTP-3EGTP-2′ c) 87.861.7 61.5 87.1 1.04 1.04 34/35/31 33/34/33 32/38/30 31/33/35 e) EGTP-3EGTP-3′ d) 97.487.8 87.1 97.0 1.04 1.02 33/34/33 39/31/30 31/33/35 37/32/31 EGTP-3 e) 97.4 97.0a) (PMMA)/PS/P2MEMA. 1.02 39/31/30 37/32/31 a) (PMMA)/PS/P2MEMA.

Polymers 2017, 9, 470 17 of 31

With the iterative methodology shown in Scheme 8, both graft and main chains are advantageously introduced at the same time. We have recently developed an alternative methodology using a living α-chain-end-(X1 and X2)-functionalized polymer (see Scheme 10) [96]. The same as Scheme 9, the X1 and X2 functionalities are TMS and TBDMS ethers and sequentially deprotected one by one to convert to the first and second PA (Y) reaction sites. The synthesis was started to prepare a living α-chain-end-(TMS and TBDMS ethers)-functionalized poly(benzyl methacrylate) (PBnMA) by the living polymerization of BnMA with the functional initiator obtained from sec-BuLi and 2. After the termination and the conversion of the TMS ether to the reaction site, a living (PMMA) reacted with the reaction site to result in an in-chain-TBDMS ether-functionalized (PMMA)–block–PBnMA. The TBDMS ether was then converted to the reaction site. The in-chain-PA- functionalized (PMMA)–block–PBnMA thus prepared was linked with a newly prepared living α- chain-end-(TMS and TBDMS ethers)-functionalized PBnMA. By this reaction, one branched unit was made and the TMS and TBDMS ethers were reintroduced. The reaction sequence was iterated twice. In each of the intermediate polymers thus obtained, the TBDMS ether was converted to the reaction site, followed by linking with a living PBnMA, to synthesize the exactly defined PBnMA–graft– PMMA with two and three (PMMA) graft chains. The results summarized in Table 8 clearly show the successful synthesis of the exactly defined (PBnMA–graft–PMMA)s. Thus, it is possible to synthesize all poly(methacrylate)-based (EDGP)s by this methodology. Needless to say, the synthesis of such (EDGP)s is difficult by the methodology shown in Scheme 8. Similarly, a series of exactly defined (PBnMA–graft–P2VPy)s were synthesized by the same methodology, in which living P2VPy was used instead of living (PMMA) in each reaction sequence. A difunctional PBnMA with the TMS and TBDMS termini was prepared by the coupling reaction of a living α-chain-end-(TMS and TBDMS ethers)-functionalized PBnMA with p,p’-xylene dibromide. When this polymer was used as the starting polymer, (EDGP)s with two, four, and six (PMMA) graft chains were readily synthesized with less repetition of the reaction sequence (only three times) (see Scheme 11).

SchemeScheme 10. Successive 10. Successive synthesis synthesis of of(EDGP)s (EDGP)s by by the the iterative iterative methodology methodology with the withuse of the living use α- of living chain-end-(X1 and X2)-functionalized polymer. Reproduced with permission from reference [96]. α-chain-end-(X1 and X2)-functionalized polymer. Reproduced with permission from reference [96]. Copyright 2015 American Chemical Society. Copyright 2015 American Chemical Society. Table 8. Characterization results of (EDGP)s by the iterative methodology.

Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) a) Polymer Calcd. RALLS SEC Calcd. 1H NMR EGTP-1′ b) 19.7 18.7 1.02 40/60 39/61 EGTP-1 c) 30.1 28.4 1.02 60/40 60/40 EGTP-2′ d) 39.3 39.1 1.02 45/55 44/56 EGTP-2 e) 49.6 49.5 1.02 56/44 55/45 EGTP-3′ f) 59.9 60.9 1.03 47/53 47/53 EGTP-3 g) 72.7 71.3 1.03 55/45 56/44 a) Determined by SEC with RI, viscometer, and right angle laser light scattering (RALLS) detector. b) APBnMA/PMMA.

Polymers 2017, 9, 470 17 of 31

Polymers 2017, 9, 470 17 of 30

The results summarized in Table8 clearly show the successful synthesis of the exactly defined (PBnMA–graft–PMMA)s. Thus, it is possible to synthesize all poly(methacrylate)-based (EDGP)s by this methodology. Needless to say, the synthesis of such (EDGP)s is difficult by the methodology shown in Scheme8. Similarly, a series of exactly defined (PBnMA– graft–P2VPy)s were synthesized by the same methodology, in which living P2VPy was used instead of living (PMMA) in each reaction sequence.

SchemeTable 10. 8.SuccessiveCharacterization synthesis of results(EDGP)s ofby (EDGP)sthe iterative by methodology the iterative with methodology. the use of living α- chain-end-(X1 and X2)-functionalized polymer. Reproduced with permission from reference [96].

Copyright 2015 American Chemical Society. a) Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) Polymer TableCalcd. 8. Characterization RALLS results of (EDGP) SECs by the iterative methodology. Calcd. 1H NMR

0 b) Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) a) EGTP-1 Polymer 19.7 18.7 1.02 40/60 39/61 1 EGTP-1 c) 30.1Calcd. RALLS 28.4 SEC 1.02 Calcd. 60/40H NMR 60/40 b) 0 d)EGTP-1′ 19.7 18.7 1.02 40/60 39/61 EGTP-2 EGTP-1 c) 39.330.1 39.128.4 1.02 1.02 60/40 45/55 60/40 44/56 EGTP-2 e)EGTP-2′ d) 49.639.3 49.539.1 1.02 1.02 45/55 56/44 44/56 55/45 EGTP-30 f)EGTP-2 e) 59.949.6 60.949.5 1.02 1.03 56/44 47/53 55/45 47/53 f) g)EGTP-3′ 59.9 60.9 1.03 47/53 47/53 EGTP-3 EGTP-3 g) 72.772.7 71.371.3 1.03 1.03 55/45 55/45 56/44 56/44 a) Determineda) Determined by SEC by withSEC with RI, RI, viscometer, viscometer, and righ rightt angle angle laserlaser light scattering light scattering (RALLS) detector. (RALLS) detector. b) APBnMA/PMMA.b) APBnMA/PMMA.

Polymers 2017, 9, 470 18 of 31

In summary, we demonstrated the successful syntheses of EDG co- and terpolymers by A difunctionaldeveloping PBnMA the three with iterative the methodologies TMS and TBDMS shown in terminiSchemes 8–10. was As prepared often suggested by the in couplingthese reaction methodologies, they are basically the same as the methodologies for the synthesis of (μ-SP)s and of a living α-chain-end-(TMS(DHBP)s. Three different and building TBDMS blocks, ethers)-functionalized i.e., living in-chain-X-functionalized PBnMA diblock with pcopolymer,,p’-xylene dibromide. When this polymerliving in-chain-( was usedX1 and as X2 the)-functionalized starting polymer,diblock copolymer, (EDGP)s and withliving two,α-chain-end-( four, andX1 and six X2)- (PMMA) graft chains were readilyfunctionalized synthesized polymer, were with employed. less repetition It should also of be thenoted reaction that the TBDMS sequence ether (X (only), TMS ether three times) (see (X1), and TBDMS ether (X2) functionalities and the BnBr or PA (Y) reaction site are the same as those Scheme 11). used in the previous methodologies.

O-Si a = MeOH, K2CO3 X1 a' = Bu4NF X O-Si 2 O i b = i N OPr 2 COOH, Ph3P, PrO N O O

O Y O

X1 Br PMMA X Br X X2 COOBn 1 1 PBnMA X1 1) a sec-BuLi X 2) b X2 2 X2

X 1 PMMA

1) a' X2 1) a X2 X2 X2 X2 2) b 2) b X1 X1

X Mn = 48.2 kg/mol, Mw/Mn = 1.03 1 PMMA

1) a' X2 1) a X2 X2 2) b 2) b X 1 X1

Mn = 87.5 kg/mol, Mw/Mn = 1.04 X1

1) a' X2 X2 X2 2) b X 1 X1

Mn = 123 kg/mol, Mw/Mn = 1.03

Scheme 11. SuccessiveScheme 11. Successive synthesis synthesis of exactly of exactly deﬁned defined (PBnMA– (PBnMA–graft–PMMA)sgraft–PMMA)s with two, withfour, and two, six four, and six (PMMA) graft chains by the iterative methodology using difunctional PBnMA as the starting polymer. (PMMA) graft chains by the iterative methodology using difunctional PBnMA as the starting polymer. 2.4. Block Polymers ((BP)s) Although (BP)s are not generally categorized in macromolecular architectures, multiblock polymers with more than three blocks are added to macromolecular architectures in this article because they are composed of several polymer segments or repeating units linked in a line. In general, well-defined (BP)s are synthesized by the sequential addition of different monomers to an appropriate anionic initiator, so-called “sequential block polymerization” [98]. Using two monomers with similar reactivities, all possible (BP)s are readily obtained without difficulty because the crossover polymerization is acceptable among these monomers. In fact, AB, ABA, BAB, and (AB)n multiblock copolymers are synthesized by the sequential block polymerization. In the case using three monomers, the syntheses of ABC, ACB, and BAC triblock terpolymers are achieved by sequentially adding the corresponding monomers to the initiator. In contrast, when monomers with different reactivities are used, the synthetically feasible (BP)s are considerably restricted because the crossover polymerization is difficult. Among these

Polymers 2017, 9, 470 18 of 30

In summary, we demonstrated the successful syntheses of EDG co- and terpolymers by developing the three iterative methodologies shown in Schemes8–10. As often suggested in these methodologies, they are basically the same as the methodologies for the synthesis of (µ-SP)s and (DHBP)s. Three different building blocks, i.e., living in-chain-X-functionalized diblock copolymer, living in-chain-(X1 and X2)-functionalized diblock copolymer, and living α-chain-end-(X1 and X2)-functionalized polymer, were employed. It should also be noted that the TBDMS ether (X), TMS ether (X1), and TBDMS ether (X2) functionalities and the BnBr or PA (Y) reaction site are the same as those used in the previous methodologies.

2.4. Block Polymers ((BP)s) Although (BP)s are not generally categorized in macromolecular architectures, multiblock polymers with more than three blocks are added to macromolecular architectures in this article because they are composed of several polymer segments or repeating units linked in a line. In general, well-defined (BP)s are synthesized by the sequential addition of different monomers to an appropriate anionic initiator, so-called “sequential block polymerization” [98]. Using two monomers with similar reactivities, all possible (BP)s are readily obtained without difficulty because the crossover polymerization is acceptable among these monomers. In fact, AB, ABA, BAB, and (AB)n multiblock copolymers are synthesized by the sequential block polymerization. In the case using three monomers, the syntheses of ABC, ACB, and BAC triblock terpolymers are achieved by sequentially adding the corresponding monomers to the initiator. In contrast, when monomers with different reactivities are used, the synthetically feasible (BP)s are considerably restricted because the crossover polymerization is difficult. Among these monomers, a less reactive chain-end anion is always produced from a more reactive monomer and vice-versa. This often causes a serious problem that a less reactive chain-end anion is not able to polymerize a less reactive monomer. As a result, no block copolymer is formed. In this section, the synthetic difficulty of (BP)s using monomers with different reactivities and how to overcome such the difficulty will be described [1,5,16,17,99–104].

2.4.1. Synthetic Possibility of Triblock Co- and Terpolymers In order to examine the synthetic possibility of triblock copolymer using two monomers with different reactivities, styrene and MMA are chosen. As is known, MMA is more reactive (or electrophilic) than styrene because of the stronger electron-withdrawing character of the carbonyl group to reduce the electron-density of the vinyl group. In contrast, the (PMMA) anion becomes less reactive (or nucleophilic) than that of PSt by the presence of the same stronger electron-withdrawing carbonyl group, which reduces electron-density of the anion. Accordingly, (PMMA) anion cannot polymerize less reactive styrene under the normal conditions, while MMA is readily polymerized with more reactive PSt anion. This means that (PMMA)–block–PSt cannot be obtained by the sequential addition of first MMA and styrene. On the other hand, less reactive styrene is first polymerized to produce the more reactive PSt anion, followed by addition of more reactive MMA, yielding PSt–block–PMMA. Thus, the monomer addition order is very critical. Due to the same reactivity problem, neither triblock copolymers of PSt–block–PMMA–block–PSt and (PMMA)–block–PSt–block–PMMA nor multiblock copolymers of PSt–block–PMMA–block–PSt–block–PMMA ... ; i.e., (PSt–block–PMMA)n can be synthesized. Thus, the synthesis of all possible (BP)s, except for PSt–block–PMMA, is difficult by the sequential block copolymerization. To overcome such synthetic difficulty, we have recently proposed a more general methodology combining living anionic sequential block copolymerization with a 1:1 addition reaction as illustrated in Scheme 12[ 100–102]. For the synthesis of PSt–block–PMMA–block–PSt, an α-chain-end- X-functionalized PSt was first prepared by the living polymerization of styrene with an X-functionalized initiator. The introduced X α-terminus was then converted to a Y reaction site. A living PSt–block–PMMA was prepared by the sequential polymerization and reacted with the Polymers 2017, 9, 470 19 of 30

Polymersα-chain-end- 2017, 9, Y470-functionalized PSt, yielding the target PSt–block–PMMA–block–PSt. A (PMMA)–20 of 31 block–PSt–block–PMMA with the opposite sequence was synthesized by the linking of a living (PMMA)reactive styrene with an veryα-chain-end- sluggishlyY -functionalizedalong with the unwanted PSt–block–PMMA. side reactions Here, during the X and the Ypolymerization.functionalities Basedare TBDMS on such ether the relationships, and PA reaction it is understan site, respectively,dable that similar the ABC to triblock several terpolymer schemes shown of PSt– inblock this– P2VPy–article. Furthermore,block–PMMA syntheticallycan be synthesized, difﬁcult but PSt– theblock syntheses–P2VPy– ofblock PSt––PSt,block P2VPy––PMMA–blockblock–PSt––P2VPyblock–P2VPy, (ACB) andP2VPy– P2VPy–blockblock–PMMA––PSt–block–PMMA–P2VPy, (BAC) and (PMMA)– are difficultblock by–P2VPy– the sequblockential–PMMA block terpolymerization were also obtained due by tothe the same monomer methodology. and anion reactivity mismatch [105–109].

Scheme 12. 12. SynthesisSynthesis of ofPSt– PSt–blockblock–PMMA––PMMA–blockblock–PSt–PSt and and (PMMA)– (PMMA)–blockblock–PSt––PSt–blockblock–PMMA–PMMA by a bynew a methodologynew methodology combining combining living living sequential sequential block block copolymerization copolymerization with with a a1:1 1:1 addition addition reaction. reaction. Reproduced with permission from reference [[100100].]. Copyright 2011 AmericanAmerican ChemicalChemical Society.Society.

Among theTable above 9. Relationships synthesized among (BCP)s, monomers P2VPy– andblock ch–PSt–ain-endblock anions–P2VPy, in polymerization. (PMMA)–block –PSt–block– PMMA, and (PMMA)–Monomeblockr –P2VPy–block–PMMA can be synthesized by the sequential addition of styrene or 2VPy and either 2VPy or MMA to an appropriate difunctional initiator. In these polymers, the P2VPy or (PMMA) both side blocks are always equal in molecular weight. Very interestingly and importantly, the proposed methodology enables to synthesize the triblock copolymers with molecularGrowing weight-asymmetryChain-End in both side blocks because the molecular weight of each side block Anion can be changed by the living anionic polymerization or sequential block copolymerization prior to PSt− the linking reaction. The following polymers were such examples: P2VPy–block–PSt–block –P2VPy (M = 19.5/10.0/10.4 kg·mol−1), (PMMA)–block–PSt–block–PMMA (M = 18.7/11.2/11.6 kg·mol−1), n − n (P2VPy) −1 and (PMMA)–block–P2VPy–block–PMMA (Mn = 6.30/12.6/20.5 kg·mol )[100]. The next(PMMA) question− is the synthetic possibility of triblock terpolymer using three monomers with different reactivities. In order to understand the synthetic situation, styrene, 2VPy, and MMA were a) used as: theHomopolymerization. three monomers. The : Living monomer polymerization. reactivity : increasesNo polymerization. from styrene, The polymerization 2VPy, to MMA in this order,proceeds while very the sluggishly reactivity along of chain-endwith unwanted anion side decreases reacions. from living PSt (hereinafter abbreviated − − − as PStThe), methodology P2VPy , to (PMMA)combining. Theirliving relationshipssequential block in the copolymerization polymerization arewith listed a 1:1 in addition Table9. − Thereaction most useful reactive for triblock PSt initiates copolymers the polymerization synthesis was also of 2VPy effective and for MMA, the synthesis which are of more the ACB reactive and BAC triblock terpolymers (see Scheme 13) [100]. To synthesize the PSt–block–PMMA–block–P2VPy (ACB), a living PSt–block–PMMA was first prepared and in situ reacted with an α-chain-end-PA- functionalized P2VPy. Similarly, the P2VPy–block–PSt–block–PMMA (BAC) could be synthesized by the linking of a living P2VPy with an α-chain-end-PA-functionalized PSt–block–PMMA.

PolymersPolymersPolymers 2017 2017, 20179, ,470 9,, 4709 , 470 20 of20 3120of of31 31 reactivereactivereactive styrene styrene styrene very very very sluggishly sluggishly sluggishly along along along with with with the the unwantedthe unwanted unwanted side side sidereactions reactions reactions during during during the the polymerization.the polymerization. polymerization. BasedBasedBased on on such on such such the the relationships,the relationships, relationships, it isit understanitis isunderstan understandabledabledable that that thatthe the ABCthe ABC ABC triblock triblock triblock terpolymer terpolymer terpolymer of ofPSt– ofPSt– PSt–blockblockblock– – –

P2VPy–P2VPy–P2VPy–blockblockblock–PMMA–PMMA–PMMAPolymers can 2017can becan, 9 be, synthesized,470 be synthesized, synthesized, but but thebut the syntheses the syntheses syntheses of ofPSt– ofPSt– PSt–blockblockblock–PMMA––PMMA––PMMA–blockblockblock–P2VPy–P2VPy–P2VPy (ACB) (ACB) (ACB)20 of 31 PolymersPolymers 2017 2017, 9, ,470 9, 470 20 of20 31of 31 PolymersPolymers 2017 2017,, 9,, 9,, ,470,470 470470 2020 of of 31 31 andand P2VPy–and P2VPy– P2VPy–blockblockblock–PSt–PolymersPolymers–PSt–Polymers–PSt–block 2017block 2017 2017,block –PMMA9, ,470 ,–PMMA9 9, ,470 –PMMA 470 (BAC) (BAC) (BAC) are are difficult are difficult difficult by by the by the sequ the sequ sequentialentialential block block block terpolymerization terpolymerization terpolymerization due due20 due of2020 31of of 31 31 to tothe tothe monomer the monomer monomer andreactive and andanion anion styrene anion reactivity reactivity veryreactivity sluggishly mismatch mismatch mismatch along [105–109]. [105–109]. with [105–109]. the unwanted side reactions during the polymerization. reactivereactivereactivereactive styrene styrenestyrene styrene very veryvery very sluggishly sluggishlysluggishly sluggishly along alongalong along with withwith with the thethe theunwanted unwanted unwanted side side side reactions reactions reactions during during during the the the polymerization. polymerization. polymerization. reactiveBasedreactivereactivereactive on styrene such styrene styrenestyrene the very veryrelationships, veryvery sluggishly sluggishly sluggishlysluggishly alongit along isalongalong understan with with withwith the the thethe dableunwanted unwanted unwanted that theside side sideABC reactions reactionsreactions triblock during during terpolymerduring the thethe polymerization. polymerization. polymerization.of PSt–block– BasedBasedBased on on onsuch such such the the the relationships, relationships, relationships, it isit it isunderstan is understan understandabledabledable that that that the the theABC ABC ABC triblock triblock triblock terpolymer terpolymer terpolymer of of PSt–of PSt– PSt–blockblockblock– –– BasedP2VPy–BasedBased onblock on onsuch such–PMMAsuch the thethe relationships, relationships,relationships,can be synthesized, it is itit understan isis understanunderstan but thedable synthesesdabledable that thatthat the of thethe ABCPSt– ABCABC blocktriblock triblocktriblock–PMMA– terpolymer terpolymerterpolymerblock–P2VPy of ofPSt–of PSt–PSt– (ACB)blockblockblock– –– P2VPy–P2VPy–P2VPy–blockblockblock–PMMA–PMMA–PMMA can can can be be synthesized,be synthesized, synthesized, but but but the the thesyntheses syntheses syntheses of of PSt–of PSt– PSt–blockblockblock–PMMA––PMMA––PMMA–blockblockblock–P2VPy–P2VPy–P2VPy (ACB) (ACB) (ACB) P2VPy–andP2VPy–P2VPy– P2VPy–blockblockblockblock–PMMA–PMMA–PMMA–PSt– canblock cancan be–PMMA bebesynthesized, synthesized,synthesized, (BAC) but are butbut the difficult thethe syntheses synthesessyntheses by the of sequ ofPSt–of PSt–PSt–entialblockblockblock–PMMA– block–PMMA––PMMA– terpolymerizationblockblockblock–P2VPy–P2VPy–P2VPy (ACB) (ACB)due(ACB) andandand P2VPy– P2VPy– P2VPy–blockblockblock–PSt––PSt––PSt–blockblockblock–PMMA–PMMA–PMMA (BAC) (BAC) (BAC) are are aredifficult difficult difficult by by theby the thesequ sequ sequentialentialential block block block terpolymerization terpolymerization terpolymerization due due due andto andtheand P2VPy– monomerP2VPy– P2VPy–blockblockblock and–PSt––PSt––PSt– anionblockblockblock –PMMAreactivity–PMMA–PMMA (BAC) mismatch (BAC) (BAC) are are are difficult [105–109]. difficult difficult by by bythe the the sequ sequ sequentialentialential block block block terpolymerization terpolymerization terpolymerization due due due to tototheto thethe themonomer monomermonomer monomer and andand and anion anionanion anion reactivity reactivityreactivity reactivity mismatch mismatchmismatch mismatch [105–109]. [105–109].[105–109]. [105–109]. to tothetoto the thethe monomer monomer monomermonomer and and andand anion anion anionanion reactivity reactivity reactivityreactivity mismatch mismatch mismatchmismatch [105–109]. [105–109]. [105–109].[105–109].

Polymers 2017, 9, 470 20 of 30

than styrene, while neither styrene nor 2VPy is polymerized with the least reactive (PMMA)−. The 2VPy− with the reactivity between PSt− and (PMMA)− polymerizes more reactive MMA, but can polymerize less reactive styrene very sluggishly along with the unwanted side reactions

during the polymerization. Based on such the relationships, it is understandable that the ABC

triblockSchemeSchemeScheme 12. terpolymer 12. Synthesis 12. Synthesis Synthesis of of ofPSt– PSt– ofPSt– blockPSt–blockblock–PMMA–block–PMMA––P2VPy––PMMA–blockblockblock–PStblock–PSt–PMMA –PStand and (PMMA)–and (PMMA)– (PMMA)– canblock beblock synthesized,–PSt–block–PSt––PSt–blockblock–PMMAblock–PMMA but–PMMA by the bya bysynthesesnew a newa new of Scheme 12. Synthesis of PSt–block–PMMA–block–PSt and (PMMA)–block–PSt–block–PMMA by a new PSt–methodologymethodologyblockmethodology–PMMA– combining combiningScheme combiningblockSchemeScheme –P2VPy12.living 12. Synthesis12.living SynthesisSynthesisliving Synthesis sequential (ACB)sequential ofsequential ofPSt–of of PSt–PSt–and PSt– blockblockblockblock block P2VPy–block–PMMA– block–PMMA– –PMMA–co polymerizationco blockcopolymerizationblockpolymerizationblockblockblock–PSt–PSt––PSt–PSt and andblock and (PMMA)– with (PMMA)– (PMMA)––PMMAwith witha block1:1a blockblockblocka1:1 –PSt– addition (BAC)1:1 –PSt––PSt–addition blockadditionblockblockblock are–PMMA reaction.–PMMA –PMMA difﬁcultreaction. reaction. by by aby new aby a new new the SchememethodologySchemeScheme 12. 12. 12.Synthesis Synthesiscombining SynthesisSynthesis of ofPSt– of ofliving PSt– PSt–PSt–blockblockblock blocksequential–PMMA––PMMA––PMMA––PMMA–block blockblockblockblock–PSt –PSt–PSt–PStco andpolymerization and andand (PMMA)– (PMMA)– (PMMA)–(PMMA)–block blockwithblockblock–PSt––PSt– –PSt––PSt–a block1:1blockblockblock –PMMAaddition–PMMA–PMMA–PMMA byreaction. by abyby new a aa new newnew sequentialReproducedReproducedReproduced block with with with terpolymerizationpermissionmethodology methodologypermissionmethodology permission from combining from combining combiningfrom reference reference due reference living toliving living[100]. the sequential[100]. sequential[ monomer100].sequentialCopyright Copyright Copyright block blockblock and2011 co 2011 polymerization co co anion2011Americanpolymerizationpolymerization American American reactivity Chemical withChemical withChemicalwith mismatcha 1:1 aSociety.a 1:1 Society.1:1addition Society. additionaddition [105 reaction. – reaction.109reaction.]. methodologyReproducedmethodologymethodology with combining combining combiningpermission living living livingfrom sequential reference sequentialsequential block[100]. blockblock Copyrightco polymerizationcocopolymerizationpolymerization 2011 American with withwith a Chemical 1:1aa 1:1 1:1addition additionaddition Society. reaction. reaction.reaction. ReproducedReproducedReproduced with with with permission permission permission from from from reference reference reference [100]. [ 100].[100]. Copyright Copyright Copyright 2011 2011 2011 American American American Chemical Chemical Chemical Society. Society. Society. ReproducedReproducedReproduced with with with permission permission permission from from from reference reference reference [100]. [ [100].100].100]. Copyright Copyright CopyrightCopyright 2011 2011 20112011 American American AmericanAmerican Chemical Chemical ChemicalChemical Society. Society. Society.Society. TableTableTable 9. Relationships9. 9.Relationships RelationshipsTable 9.among Relationships among among monomers monomers monomers among and monomersand ch andand ain-endch chain-endchain-endain-end and anions ch anionsain-end anionsanions in polymerization.in anions ininpolymerization. polymerization.polymerization. in polymerization. TableTableTable 9. Relationships9. 9. RelationshipsRelationships Relationships among amongamong among monomers monomersmonomers monomers and andand and ch ain-endchch chain-endain-end anions anions anions in inpolymerization. in polymerization. polymerization. TableTableTable 9. Relationships9. 9. Relationships RelationshipsRelationships among among amongamong monomers monomers monomersmonomers and and andand ch ain-endch chchain-endain-endain-end anions anions anionsanions in polymerization.in inin polymerization. polymerization.polymerization. MonomeMonomeMonomer r r Monomer MonomeMonomeMonomer rr r MonomeMonomeMonomer rrr

Monomer Growing Chain-End Anion Growing Chain-End Growing Chain-End GrowingGrowingGrowing Chain-End Chain-End Chain-EndGrowingGrowing Growing Anion Chain-End Chain-End Chain-End GrowingGrowingGrowing Chain-EndAnion Chain-EndChain-End AnionAnionAnion AnionAnionAnion AnionAnionAnion PSt − − − −−− − − PSt PStPStPSt− − − PStPSt PSt − PStPStPSt− −− (P2VPy)− − −−− (P2VPy)(P2VPy)−(P2VPy)(P2VPy)− − − (P2VPy)(P2VPy)(P2VPy)− −(P2VPy) − (P2VPy)(P2VPy)(P2VPy)(P2VPy)− −− (PMMA)− − −−− (PMMA)(PMMA)(PMMA)(PMMA)− − − (PMMA)(PMMA)(PMMA)−(PMMA)− −− (PMMA)(PMMA)(PMMA)− :− Homopolymerization. − (PMMA)(PMMA)(PMMA) : Living polymerization. : No polymerization. a) The polymerization a) a)a) a)a) : Homopolymerization.:: :Homopolymerization.Homopolymerization. Homopolymerization. : Living : : :LivingLiving Living po polymerization.po polymerization.lymerization.lymerization. : No : : :NoNo Nopolymerization. polymerization.polymerization. polymerization. a) The a) a) TheThe The polymerization polymerizationpolymerization polymerization proceeds: Homopolymerization.: :: Homopolymerization. Homopolymerization.Homopolymerization. very sluggishly along : Living with : : : Living LivingLiving unwanted po polymerization. popolymerization.lymerization.lymerization. side reacions. : No : : : No NoNo polymerization. polymerization. polymerization.polymerization. a) The a) a) The TheThe polymerization polymerization polymerizationpolymerization : Homopolymerization.: Homopolymerization.: Homopolymerization.proceedsproceedsproceeds very very very : Livingsluggishly :: sluggishlyLiving sluggishly : Living po polymerization.alongpolymerization. alongpo lymerization.along lymerization.with with with unwanted unwanted unwanted : No :side No polymerization.side :polymerization. sideNo reacions. polymerization. reacions. reacions.polymerization. a) a)The The a) polymerization Thea) polymerizationThe polymerization polymerization proceeds proceedsproceedsproceeds very very very sluggishly sluggishly sluggishly along along along with with with unwanted unwanted unwanted side side side reacions. reacions. reacions. very sluggishlyThe alongproceeds methodology with unwantedvery sluggishly combining side reacions. along livingwith unwanted sequential side blockreacions. copolymerization with a 1:1 addition proceedsproceedsproceeds very very verysluggishly sluggishlyThe sluggishlyTheThe methodology methodologyalongmethodology along along with with withunwantedcombining combiningunwantedcombining unwanted sideliving side livingliving reacions.side reacions.sequential reacions. sequentialsequential block blockblock copolymerization copolymerizationcopolymerization with withwith a a1:1a 1:1 1:1addition additionaddition reactionTheTheThe usefulmethodology methodologymethodology for triblock combining combining combiningcopolymers living livingliving synthesis sequential sequentialsequential was alsoblock blockblock effective copolymerization copolymerizationcopolymerization for the synthesis with withwith ofa the1:1aa 1:1 1:1ACBaddition additionaddition and reactionreactionreactionreaction useful usefuluseful useful for forfor fortriblock triblocktriblock triblock copolymers copolymerscopolymers copolymers synthesis synthesissynthesis synthesis was waswas was also alsoalso also effective effectiveeffective effective for forfor forthe thethe thesynthesis synthesissynthesis synthesis of ofof theof thethe theACB ACBACB ACB and andand and TheThe Themethodology methodology methodologyreactionBACreactionreactionreaction triblock combininguseful combininguseful usefuluseful combining terpolymers for for for fortriblock triblock livingtriblocktriblock living living(seecopolymers copolymerssequential copolymerscopolymers Schemesequential sequential synthesis13) synthesis synthesissynthesisblock [100].block block was copolymerizationTo was waswascopolymerization synthesizealsocopolymerization also alsoalso effective effective effectiveeffective the for PSt– for for forthewith theblock thewiththe synthesis with synthesis synthesisasynthesis–PMMA– 1:1a a1:1 ofaddition1:1 of theofadditionblockof the additionthethe ACB–P2VPy ACB ACBACB and and andand The methodologyBACBACBAC triblock triblock triblock combining terpolymers terpolymers terpolymers living (see (see (see sequentialScheme Scheme Scheme 13) 13) block 13)[100]. [100]. [100]. copolymerization To To Tosynthesize synthesize synthesize the the thePSt– with PSt– PSt–block ablockblock 1:1–PMMA––PMMA– addition–PMMA–blockblock reactionblock–P2VPy–P2VPy–P2VPy reactionreactionreaction useful useful useful forBAC(ACB), for triblockBAC BACfor triblocktriblock triblock atriblocktriblock living copolymers terpolymerscopolymers terpolymersPSt–copolymersterpolymersblock –PMMAsynthesis (see synthesis (see(see synthesis Scheme SchemeSchemewas was wasfirst13) wasalso 13)13) [100]. preparedalso [100]. [100].alsoeffective effectiveTo effective To To synthesizeand synthesizesynthesize for in for the situfor the the synthesisthe reacted the the synthesisPSt– synthesis PSt–PSt–block withblockblock of–PMMA– ofthean–PMMA––PMMA– ofthe α ACBthe-chain-end-PA- ACBblock ACB blockandblock –P2VPyand –P2VPy–P2VPyand useful for triblock(ACB),(ACB),(ACB),(ACB), copolymersa livinga aa living livingliving PSt– PSt– PSt–PSt–block synthesisblockblock–PMMA–PMMA–PMMA was was was was alsofirst first first effectiveprepared prepared prepared and for and and thein in situin synthesissitu situ reacted reacted reacted with of with with the an an ACBanα -chain-end-PA-α α-chain-end-PA--chain-end-PA--chain-end-PA- and BAC (ACB),functionalized(ACB),(ACB),(ACB), a living aaa livinglivingliving P2VPy. PSt– PSt–PSt–PSt–block blockSimilarly,block–PMMA–PMMA–PMMA the was wasP2VPy–was first firstfirst preparedblock preparedprepared–PSt– andblock andand in–PMMA insituin situsitu reacted reacted(BAC)reacted with could withwith an bean anα -chain-end-PA- synthesized αα-chain-end-PA--chain-end-PA--chain-end-PA- by BACBACBAC triblock triblock triblock terpolymers terpolymers terpolymersfunctionalized (see (see (see SchemeP2VPy. Scheme Scheme Similarly, 13) 13) [100].13) [100]. [100].the To P2VPy– To synthesize To synthesize synthesizeblock–PSt– the theblock PSt–the PSt––PMMA PSt–blockblockblock–PMMA– (BAC)–PMMA––PMMA– couldblockblock beblock–P2VPy synthesized–P2VPy–P2VPy by triblock terpolymersfunctionalizedthefunctionalizedfunctionalized linking (see of a SchemeP2VPy. living P2VPy. P2VPy. P2VPy Similarly, 13 Similarly, Similarly,)[ 100with ].the an Tothe the P2VPy– α synthesize -chain-end-PA-functionalizedP2VPy– P2VPy–blockblockblock–PSt– the–PSt––PSt–block PSt–blockblock–PMMAblock–PMMA–PMMA–PMMA– (BAC)PSt– (BAC) (BAC)block couldblock could –PMMA.could be–P2VPy be synthesizedbe synthesized synthesized (ACB), by by by (ACB),(ACB),(ACB), a livinga livinga living PSt–functionalized PSt–functionalizedfunctionalized PSt–blockblockblock–PMMA–PMMA –PMMAP2VPy. P2VPy.P2VPy. was wasSimilarly, was Similarly,firstSimilarly, first firstprepared theprepared thepreparedthe P2VPy– P2VPy–P2VPy– and blockand blockandblockin –PSt– insitu –PSt––PSt– insitu block situreactedblock blockreacted–PMMA reacted–PMMA–PMMA with with (BAC) with (BAC)an(BAC) an α couldan-chain-end-PA- αcouldcould -chain-end-PA-α -chain-end-PA-be bebesynthesized synthesizedsynthesized by by by a living PSt–blockthethethethe linking–PMMA linkinglinking linking of ofof a wasof living aa a livingliving living ﬁrst P2VPy P2VPypreparedP2VPy P2VPy with withwith with an and anan αan-chain-end-PA-functionalized α in α-chain-end-PA-functionalized-chain-end-PA-functionalized-chain-end-PA-functionalized situ reacted with an α-chain-end-PA-functionalized PSt– PSt–PSt– PSt–blockblockblock–PMMA.–PMMA.–PMMA. functionalizedfunctionalizedfunctionalized P2VPy. the P2VPy. theP2VPy.the linking linking linkingSimilarly, Similarly, ofSimilarly, ofaof living aa livinglivingthe the P2VPy P2VPy–the P2VPy P2VPyP2VPy– P2VPy– with withblockwith anblock block an–PSt–anα-chain-end-PA-functionalized –PSt– αα-chain-end-PA-functionalized-chain-end-PA-functionalized–PSt–blockblockblock–PMMA–PMMA–PMMA (BAC) (BAC) (BAC) could PSt–could PSt–couldPSt– blockbe blockblockbe synthesized –PMMA.be synthesized–PMMA.–PMMA. synthesized by by by P2VPy. Similarly, the P2VPy–block–PSt–block–PMMA (BAC) could be synthesized by the linking of a thethe linkingthe linking linking of ofa living ofa livinga living P2VPy P2VPy P2VPy with with with an an α an-chain-end-PA-functionalized α -chain-end-PA-functionalizedα-chain-end-PA-functionalized PSt– PSt– PSt–blockblockblock–PMMA.–PMMA.–PMMA. living P2VPy with an α-chain-end-PA-functionalized PSt–block–PMMA. Both P2VPy–block–PMMA–block–PSt (BCA) and (PMMA)–block–PSt–block–P2VPy (CAB) are considered to be the same in structure as the ACB and BAC. However, another synthetic design is possible for these polymers (see also Scheme 13). A P2VPy–block–PMMA–block–PSt (BCA) was synthesized by the linking of a living P2VPy-block-PMMA with a PSt with the PA α-terminus. Similarly, a (PMMA)–block–PSt–block–P2VPy (CAB) was obtained by the reaction of a living (PMMA) with an α-chain-end-PA-functionalized PSt-block-P2VPy. Their requisite structures were evident (see Table 10)[100].

Table 10. Characterization results of ABC, ACB, BAC, BCA, and CAB triblock terpolymers.

Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) Polymer Calcd. RALLS SEC Calcd. 1H NMR ABC 40.5 40.0 1.04 33/34/33 32/35/33 ACB 32.2 34.6 1.04 25/58/17 27/54/19 BAC 28.9 30.1 1.05 32/34/34 31/34/35 BCA 37.2 38.2 1.04 32/35/33 31/37/32 CAB 34.0 34.3 1.04 31/33/36 29/37/34 A, B and C blocks are PSt, P2VPy, and (PMMA), respectively.

Using monomers with different reactivities, the synthesis of all possible triblock co- and terpolymers, except for the ABC type, is difficult by the sequential block polymerization because of the mismatch among monomer electrophilicities and chain-end anion nucleophilicities. To overcome Polymers 2017, 9, 470 21 of 30 the difficulty, the new methodology combining living sequential block copolymerization with a 1:1 addition reaction has been proposed and found to allow access to such synthetically difficult triblock co- and terpolymers without consideration about the monomer and anion reactivities. Previously, several research groups also reported the efficient methodologies to overcome the synthetic difficulty of block polymers using monomers with different reactivities [110–120]. It is believed that the present methodology herein proposed seems to be more general in synthesis than those previous methodologies. The related block polymers can also be synthesized by the living/controlled radical polymerization or the combination of living/controlled radical polymerization with Click reactions. However, the resulting block polymers always possess relatively broadPolymers molecular 2017, 9, 470 weight distributions [121–126]. 21 of 31

Scheme 13. Synthesis of ACB and BAC as well as BCA and CAB triblock terpolymers by the Scheme 13. Synthesis of ACB and BAC as well as BCA and CAB triblock terpolymers by the methodology combiningcombining linking linking chemistry chemistry with livingwith sequentialliving sequential block copolymerization. block copolymerization. Reproduced withReproduced permission with from permission reference from [100 reference]. Copyright [100]. 2011 Copyright American 2011 Chemical American Society. Chemical Society.

Both P2VPy–block–PMMA–block–PSt (BCA) and (PMMA)–block–PSt–block–P2VPy (CAB) are considered to be the same in structure as the ACB and BAC. However, another synthetic design is possible for these polymers (see also Scheme 13). A P2VPy–block–PMMA–block–PSt (BCA) was synthesized by the linking of a living P2VPy-block-PMMA with a PSt with the PA α-terminus. Similarly, a (PMMA)–block–PSt–block–P2VPy (CAB) was obtained by the reaction of a living (PMMA) with an α-chain-end-PA-functionalized PSt-block-P2VPy. Their requisite structures were evident (see Table 10) [100]. Using monomers with different reactivities, the synthesis of all possible triblock co- and terpolymers, except for the ABC type, is difficult by the sequential block polymerization because of the mismatch among monomer electrophilicities and chain-end anion nucleophilicities. To overcome the difficulty, the new methodology combining living sequential block copolymerization with a 1:1 addition reaction has been proposed and found to allow access to such synthetically difficult triblock co- and terpolymers without consideration about the monomer and anion reactivities.

Polymers 2017, 9, 470 22 of 30

2.4.2. Multiblock Copolymer Synthesis The methodology shown in Scheme 12 was extended to the iterative methodology to synthesize multiblock copolymers of (PSt–block–PMMA)n (see Scheme 14)[99]. In this methodology, a living α-chain-end-TBDMS ether-functionalized PSt–block–PMMA is utilized as the building block to simultaneously introduce both PSt and (PMMA) blocks. In the ﬁrst sequence, the living α-chain-end-TBDMS ether-functionalized PSt–block–PMMA was prepared and, after the termination, the introduced TBDMS ether was converted to the PA reaction site. The PA-functionalized PSt–block–PMMA was linked with a newly prepared living α-chain-TBDMS ether-functionalized PSt–block–PMMA to yield an ABAB tetrablock copolymer of PSt–block–PMMA–block–PSt–block–PMMA ((PSt–block–PMMA)2). Since the TBDMS ether α-terminus is present, the reaction sequence is possible to be iterated. Indeed, the reaction sequence was further iterated to synthesize a hexablock, octablock,

Polymersand even 2017 decablock, 9, 470 copolymer of (PSt–block–PMMA)5. 23 of 31

SchemeScheme 14. 14. SynthesisSynthesis of of (PS– (PS–blockblock–PMMA)–PMMA)n ((nn == 1–5) 1–5) by by the the iterative iterative meth methodology.odology. Reproduced Reproduced with with permission from reference [[99].99]. Copy Copyrightright 2011 American Chemical Society.

Table 11. Characterization results of (PS–block–PMMA)n, (PS–block–PtBMA)n and (PS–block–P2VP)n As shown in Table 11, the resulting multiblock copolymers all possessed precisely controlled synthesized by the iterative methodology. Mn values and compositions, and low polydispersity indexes. Thus, requisite and well-deﬁned multiblock copolymers upM ton (kg/mol) a decablock typeM werew/Mn successfullyComposition synthesized. (wt % wt As % everywt %) reaction Polymer sequence proceeded almostCalcd. quantitatively, RALLS all of the SEC multiblock copolymers Calcd. were obtained1H-NMR in ca. 100% PS–b–PMMA 10.5 11.4 1.03 50/50 48/52 yields. As the ﬁnal (PSt–block–PMMA)5 still possesses the TBDMS ether α-terminus, the reaction sequence(PS– canb–PMMA) be further2 iterated.26.4 Two 28.2 more multiblock 1.03 copolymers 46/54 comprising PSt and 47/53 either (PtBMA) (PS–b–PMMA)3 37.0 40.5 1.03 45/55 43/57 or P2VPy were also synthesized (see also Table 11)[99]. The linking reaction between the two diblock (PS–b–PMMA)4 51.0 53.6 1.04 45/55 43/57 copolymers and conversion to the reaction site in each sequence are equal to the “polymer chain (PS–b–PMMA)5 64.5 66.4 1.06 45/55 45/55 introduction” and “regeneration of the reaction site” steps. Thus, the iterative methodology herein (PS–b–PtBMA)2 24.0 25.8 1.03 47/53 46/54 developed(PS–b also–PtBMA) effectively3 41.5 worked for 46.6 the synthesis 1.06 of multiblock 48/52 copolymers. 46/54 (PS–b–P2VP)2 24.3 25.3 1.04 49/51 49/51 (PS–b–P2VP)3 37.2 38.3 1.03 49/51 48/52

As illustrated in Scheme 15, the same multiblock copolymers can be obtained by the similar methodology using a living α-chain-end-X-functionalized polymer as the building block. However, the use of living α-chain-end-X-functionalized diblock copolymer is much more preferable because of the reaction step reduction. The synthesis of (ABC)n multiblock terpolymers may be feasible by the methodology with the use of living α-chain-end-X-functionalized ABC triblock terpolymer and is now under study.

Polymers 2017, 9, 470 23 of 30

t Table 11. Characterization results of (PS–block–PMMA)n, (PS–block–P BMA)n and (PS–block–P2VP)n synthesized by the iterative methodology.

Mn (kg/mol) Mw/Mn Composition (wt % wt % wt %) Polymer Calcd. RALLS SEC Calcd. 1H NMR PS–b–PMMA 10.5 11.4 1.03 50/50 48/52 (PS–b–PMMA)2 26.4 28.2 1.03 46/54 47/53 (PS–b–PMMA)3 37.0 40.5 1.03 45/55 43/57 (PS–b–PMMA)4 51.0 53.6 1.04 45/55 43/57 (PS–b–PMMA)5 64.5 66.4 1.06 45/55 45/55 t (PS–b–P BMA)2 24.0 25.8 1.03 47/53 46/54 t (PS–b–P BMA)3 41.5 46.6 1.06 48/52 46/54 (PS–b–P2VP)2 24.3 25.3 1.04 49/51 49/51 (PS–b–P2VP)3 37.2 38.3 1.03 49/51 48/52

Scheme 15. Synthesis of multiblock copolymers by the iterative methodology using a living α-chain- Scheme 15. Synthesis of multiblock copolymers by the iterative methodology using a living end-X-functionalized polymer. α-chain-end-X-functionalized polymer. It is believed that the syntheses of triblock copolymers, triblock terpolymers except for the ABC type,It and is multiblock believed that copolymers the syntheses are difficult of triblock by the direct copolymers, sequential triblock block co- terpolymers and terpolymerization except for theusing ABC monomers type, and with multiblock different copolymersreactivities. areThe difﬁcultmethodology by the combining direct sequential living sequential block co- block and terpolymerizationcopolymerization usingwith monomersa 1:1 addition with reaction different and reactivities. the extended The methodology iterative methodology combining livinghave sequentialdemonstrated block the copolymerization useful means to with successfully a 1:1 addition synt reactionhesize such and the(BP)s extended difficult iterative by sequential methodology block havepolymerization. demonstrated the useful means to successfully synthesize such (BP)s difﬁcult by sequential block polymerization. 3. Concluding Remarks and Future Outlook 3. Concluding Remarks and Future Outlook Throughout this article, we have demonstrated the successful development of a novel all-around Throughout this article, we have demonstrated the successful development of a novel all-around iterative methodology for the syntheses of multicomponent (μ-SP)s, high generation (DHBP)s, iterative methodology for the syntheses of multicomponent (µ-SP)s, high generation (DHBP)s, (EDGP)s, (EDGP)s, and multiblock polymers with more than three blocks. In this methodology, two reaction and multiblock polymers with more than three blocks. In this methodology, two reaction steps, steps, i.e., the polymer chain introduction and the regeneration of the same reaction site, are involved i.e., the polymer chain introduction and the regeneration of the same reaction site, are involved in each reaction sequence and iterated to construct the above-mentioned polymers. The following in each reaction sequence and iterated to construct the above-mentioned polymers. The following key building block is individually designed and used on the basis of their architectures: living chain- key building block is individually designed and used on the basis of their architectures: living end-X-functionalized polymer (Scheme 1), living α-chain-end-((X)2 or (X)4)-functionalized polymer chain-end-X-functionalized polymer (Scheme1), living α-chain-end-((X)2 or (X)4)-functionalized (Schemes 4–6), living in-chain-X-functionalized diblock copolymer (Scheme 8), living in-chain-(X1 polymer (Schemes4–6), living in-chain- X-functionalized diblock copolymer (Scheme8), living and X2)-functionalized diblock copolymer (Scheme 9), living α-chain-end-(X1 and X2)-functionalized in-chain-(X and X )-functionalized diblock copolymer (Scheme9), living α-chain-end-(X and polymer (Scheme1 10),2 and living α-chain-end-X-functionalized diblock copolymer (Scheme 14).1 The X, X1, and X2 functionalities are TBDMS ether, TMS ether, and TBDMS ether convertible to the BnBr or PA reaction site. In certain cases, the functional anions with TMS (X1), TBDMS (X2), and THP ethers (X3) are employed (Schemes 2 and 3) instead of living functionalized polymers. One more important advantage of this methodology is that the use of complicated multistep selective reactions and reaction site with different reactivities generally required for macromolecular architecture synthesis are completely avoided because the polymer segment(s) are introduced one by one in each reaction step. As often mentioned, all the iterative methodologies herein developed are basically the same in concept as the all-around iterative methodology mentioned in introduction. As the future synthetic potential, it is expected that different key building blocks can be employed together in the same methodology to result in the synthesis of more complex macromolecular architectures with mixed structures. Thus, synthetic limitation and difficulty of macromolecular architectures have been greatly surpassed with the progress of the iterative methodology.

Acknowledgments: This work was partly supported by a Grant-in-Aid for Scientific Research from the Japan Society of the Promotion of Science (JP15K17907 for R. G.) and Mizuho Foundation for the Promotion of Sciences (2016−2018 for R. G.).

Author Contributions: Akira Hirao and Raita Goseki conceived the topic of the article; Raita Goseki, Shotaro Ito, Yuri Matsuo, and Tomoya Higashihara designed the overall structure of the article and reviewed the literature; all authors co-wrote and edited the article.

Conflict of Interest: The authors declare no conflict of interest.

Polymers 2017, 9, 470 24 of 30

X2)-functionalized polymer (Scheme 10), and living α-chain-end-X-functionalized diblock copolymer (Scheme 14). The X, X1, and X2 functionalities are TBDMS ether, TMS ether, and TBDMS ether convertible to the BnBr or PA reaction site. In certain cases, the functional anions with TMS (X1), TBDMS (X2), and THP ethers (X3) are employed (Schemes2 and3) instead of living functionalized polymers. One more important advantage of this methodology is that the use of complicated multistep selective reactions and reaction site with different reactivities generally required for macromolecular architecture synthesis are completely avoided because the polymer segment(s) are introduced one by one in each reaction step. As often mentioned, all the iterative methodologies herein developed are basically the same in concept as the all-around iterative methodology mentioned in introduction. As the future synthetic potential, it is expected that different key building blocks can be employed together in the same methodology to result in the synthesis of more complex macromolecular architectures with mixed structures. Thus, synthetic limitation and difﬁculty of macromolecular architectures have been greatly surpassed with the progress of the iterative methodology.

Acknowledgments: This work was partly supported by a Grant-in-Aid for Scientific Research from the Japan Society of the Promotion of Science (JP15K17907 for R. G.) and Mizuho Foundation for the Promotion of Sciences (2016−2018 for R. G.). Author Contributions: Akira Hirao and Raita Goseki conceived the topic of the article; Raita Goseki, Shotaro Ito, Yuri Matsuo, and Tomoya Higashihara designed the overall structure of the article and reviewed the literature; all authors co-wrote and edited the article. Conflicts of Interest: The authors declare no conflict of interest.

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