Structural Effect of Organic Catalytic Pairs Based on Chiral Amino(thio)ureas and Phosphazene Bases for the Isoselective Ring-Opening Polymerization of Racemic Lactide

Abstract

Polymer materials featuring stereocontrolled monomer units often exhibit drastically different properties than their stereorandom counterparts. Control over the polymer tacticity thus represents a powerful means to access functional polymers of modular thermomechanical properties. In the present work, a series of chiral amino(thio)ureas (U1, TU1–TU5) are used in duos with phosphazene organic bases for the stereoselective ring-opening polymerization (ROP) of racemic lactide (rac-LA). These chiral binary organocatalytic pairs allow for relatively fast, highly chemo- and isoselective ROP of rac-LA at room temperature in toluene, yielding semicrystalline and metal-free stereoblock-like materials based on polylactide (PLA), with a melting temperature in the range 138–176 °C. The chiral dimethylaminourea, denoted as U1, shows faster ROP reactions relative to its dimethylaminothiourea TU1 analogue, when combined with any of the phosphazene bases, consistent with the formation of less stable intermediates from the urea relative to the more acidic thiourea-containing counterpart. On the other hand, the tethered dialkylamino moiety of TU1–TU3 is shown to have a non-innocent role both in the catalytic activity and the isoselectivity of the ROP process, whereby decreasing the basicity of this group leads to a decrease in the reaction rates. The active mechanism also proves to be dependent on the identity of the amino(thio)urea and the phosphazene base, and a mechanistic rationale for the experimental results is presented. Thus, the strongest organic base used in conjunction with U1 and TU1–TU5, leading to a high polymerization rate but lesser stereocontrol, induces an ionic-like mechanism. In contrast, organocatalytic pairs based on the least basic phosphazene favor a more associative mechanism involving hydrogen bond interactions, providing slower ROP reactions, but producing highly isotactic PLAs.

Ring-Opening Polymerization of Cyclic Esters and Carbonates with (Thio)urea/Cyclopropenimine Organocatalytic Systems

“…Here, we surveyed a series of CPI bases ( 1 – 7 ) in combination with U-1 for the room temperature polymerization of rac -LA (Table ). Each of the catalyst systems exhibited modest stereoselectivity, yielding PLAs with isotacticities ranging from Pm = 0.74–0.79, as determined by homonuclear decoupled 1 H NMR measurements. , While higher stereoselectivities have been observed with other (thio)­urea/base pairs, ,, the high activities for these urea/CPI catalysts (Tables and ) illustrate the range of reactivities and stereoselectivities that can be obtained by appropriate cocatalyst combinations.…”

“…Previously, bases such as 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU), , N -heterocyclic carbenes (NHCs), , or phosphazene derivatives − have been used with success to provide highly active and/or (stereo)­selective OROPs when used in combination with (thio)­ureas. To expand the range of bases used with urea cocatalysts, we targeted cyclopropenimines (CPIs) as a class of accessible, soluble, stable, tunable, and inexpensive bases as cocatalysts with (thio)­ureas.…”

“…The application of (thio)­urea/CPI organocatalytic systems for the stereoregular synthesis of PLA from rac -LA was investigated. The stereoselective polymerization of lactide has been reported for a variety of achiral and chiral catalysts. − ,− For achiral catalysts, stereoselective polymerization of rac -LA occurs by a chain-end control mechanism, where the stereochemistry of the last-enchained unit exhibits a preference for enchaining monomers of similar configuration . We and others had previously shown that sterically demanding achiral N -heterocyclic carbenes can exhibit high stereoselectivity for the polymerization of rac -LA.…”

Contrasting Roles of Counterions in Anionic Ring-Opening Polymerization Mediated by Heterocycle Organocatalysts

“…Organocatalytic ring-opening polymerization (ROP) is a powerful method for generating polyesters and polycarbonates with exquisite control over the molecular weight and molecular weight distribution. − Guanidine and (thio)­urea/base catalyst systems were among the first highly selective organocatalysts, demonstrating good control over molecular weight and dispersity. − The development of anionic catalysts based on deprotonated (thio)­ureas marked a significant advance, as these catalysts retained the high selectivity of the (thio)­urea/base catalysts but were significantly more active. Moreover, their activities can be tuned by over 3 orders of magnitude by altering substituents on the (thio)­ureas. − Due to the versatility of the anionic (thio)­urea catalysts, they have been widely adopted for the ROP of various monomers. − Mechanistic and computational studies − indicate that the activity of the anionic (thio)­urea catalysts derive from a bifunctional activation mechanism where the negatively charged nitrogen activates the propagating (or initiating) alcohol and the adjacent N–H hydrogen bond binds and positions the lactone to facilitate nucleophilic attack and formation of the tetrahedral intermediate (Figure a). − …”

Organocatalytic Group Transfer Polymerization of N,N-Diethylsorbamide Leading to trans-1,4-Addition Polymer: Controlled/Living Nature Applied to the One-Pot Synthesis of Block Copolymer with Poly(N,N-dimethylacrylamide)

“…The use of organocatalysts, also known as metal-free catalysts, has considerably progressed in organic chemistry since 2000. − In polymer chemistry, the ring-opening polymerization of lactide using 4-(dimethylamino)­pyridine as a catalyst was reported in 2002 as the first living polymerization using an organocatalyst . Organocatalytic polymerization has been widely expanded to use applicable cyclic monomers, such as cyclic esters, cyclic carbonates, and epoxides, and copolymerization of epoxide with CO 2 . − These new precision polymerization systems require improvement in terms of polymerization activity, chemical selectivity, and polymer structure control. As a different type of polymerization, the group transfer polymerization (GTP) of polar monomers using 1-trimethylsiloxy-1-methoxy-2-methyl-1-propene (silyl ketene acetal, SKA Me ) enables the controlled/living system. − Taton et al and Waymouth et al reported that N -heterocyclic carbene efficiently organocatalyzed the GTPs of methyl methacrylate and tert -butyl acrylate and the block GT copolymerization (GTcoP) of n -butyl acylate, N , N -dimethylaminoethyl acrylate, N , N -dimethylaminoethyl methacrylate, N , N -dimethylacrylamide (DMAm), and methacrylonitrile. − We have reported that several types of organic molecules categorized as strong Bro̷nsted acids of trifluoromethanesulfonimide (Tf 2 NH) and pentafluorophenylbis­(triflyl)­methane (C 6 F 5 CHTf 2 ), strong Lewis acids of N -(trimethylsilyl)­bis­(trifluoromethanesulfonyl)­imide (Me 3 SiNTf 2 ) and tris­(pentafluorophenyl)­borane (B­(C 6 F 5 ) 3 ), and organic superbases of 1- tert -butyl-4,4,4-tris­(dimethylamino)-2,2-bis­[tris­(dimethylamino)­phosphoranylidenamino]-2Λ5,4Λ5-catenadi­(phosphazene) ( t -Bu-P 4 ) and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]­undecane (T i BP) have effectively catalyzed the controlled/living GTP of (meth)­acrylate and acrylamide monomers. − An optimal organocatalyst/initiator combination is crucial to achieving a controlled/living GTP.…”