BDI Ligand Research Articles

A π-extended β-diketiminate ligand via a templated Scholl approach.

We report a templated Scholl oxidation strategy for the preparation of the first β-diketiminate (BDI) ligands embedded within a 24-electron π-system backbone. The resulting benzo[f,g]tetracene BDI ligand was coordinated to a zinc centre and electrochemical studies showed the redox active nature of the ligand.

Synthesis of a Novel Hybrid Ligand System Incorporating Classic Moieties through Acylation of 2,3,3‐Trimethylindolenine

AbstractIn main group chemistry, the BDI ligand ([HC(C(Me)N(R))2]), more commonly known as NacNac, has proved indispensable over the last two decades. Within this work, we are introducing the hybrid NacNac‐akin ligand 3,3‐dimethyl‐2‐[2‐methyl‐2‐(2,6‐diisopropyl‐aniline)ethenyl]‐3H‐indolenine (DNI). On the basis of this novel ligand, alkali metal complexes [DNI(M1)] [M1=Li (3(OEt2)), Na (4(THF)3), and K (5(THF)3)] have been synthesized by facile deprotonation of the ligand's backbone. The reaction of DNI with AlH3 ⋅ NMe2Et led to the aluminium dihydride compound [DNI‐AlH2] (6) in excellent yield (90 %). Further synthesis of [DNI‐AlI2] (7), which is seen as a potential precursor for the aluminium(I) complex, was realized in the presence of 1.0 equiv. iodine with 6. All products 2–7 were completely characterized by 2D‐NMR, mass spectrometry, elemental analysis and SC‐XRD. Density functional theory calculations were performed to provide better understanding of their bonding characteristics and electronic structures.

Expanding the Utility of β-Diketiminate Ligands in Heavy Group VI Chemistry of Molybdenum and Tungsten.

We report the synthesis of 17 molybdenum and tungsten complexes supported by the ubiquitous BDI ligand framework (BDI = β-diketiminate). The focal entry point is the synthesis of four molybdenum and tungsten(V) BDI complexes of the general formula [MO(BDIR)Cl2] [M = Mo, R = Dipp (1); M = W, R = Dipp (2); M = Mo, R = Mes (3); M = W, R = Mes (4)] synthesized by the reaction between MoOCl3(THF)2 or WOCl3(THF)2 and LiBDIR. Reactivity studies show that the BDIDipp complexes are excellent precursors toward adduct formation, reacting smoothly with dimethylaminopyridine (DMAP) and triethylphosphine oxide (OPEt3). No reaction with small phosphines has been observed, strongly contrasting the chemistry of previously reported rhenium(V) complexes. Additionally, the complexes 1 and 2 are good precursors for salt metathesis reactions. While 1 can be chemically reduced to the first stable example of a Mo(IV) BDI complex 15, reduction of 2 resulted in degradation of the BDI ligand via a nitrene transfer reaction, leading to MAD (4-((2,6-diisopropylphenyl)imino)pent-2-enide) supported tungsten(V) and tungsten(VI) complexes 16 and 17. All reported complexes have been thoroughly studied by VT-NMR and (heteronuclear) NMR spectroscopy, as well as UV-vis and EPR spectroscopy, IR spectroscopy, and X-ray diffraction analysis.

Synthesis, Structure, and Reactivity of a Superbulky Low-Valent β-Diketiminate Al(I) Complex

Low-valent β-diketiminate Al(I) complexes are generally synthesized in low yields (<20%). This is due to an intermolecular decomposition reaction. A new β-diketiminate Al(I) complex with a very bulky β-diketiminate ligand DIPePBDI was obtained in a high yield (81%) and the raw product was found to be essentially pure (DIPePBDI = HC[C(Me)N(DIPeP)]2; DIPeP = 2,6-C(H)Et2-phenyl). The crystal structure of (DIPePBDI)Al shows a monomeric complex. The reaction of (DIPePBDI)Al with AlBr3 gave (DIPePBDI)AlBr2 and Al(0). The reaction of (DIPePBDI)Al with KCH(SiMe3)2 led to deprotonation of a backbone Me group and formation of a K aluminyl complex. A minor side-product in which the BDI ligand was cleaved is also described. The very high yield of (DIPePBDI)Al makes it a welcome addition to the family of β-diketiminate Al(I) complexes.

Nucleophilic Magnesium Silanide and Silaamidinate Derivatives.

Density functional theory (DFT) calculations demonstrate that the previously reported reaction of [(BDI)Mg-n-Bu] (BDI = HC{(Me)CN-Dipp}2; Dipp = 2,6-diisopropylphenyl) with the silaborane Me2PhSi-Bpin provides the magnesium silanide derivative [(BDI)MgSiMe2Ph], through the intermediacy of a short-lived silyl-pinacolato-organoborate species. The nucleophilic character of the resultant silanide anion is assayed through a series of reactions with RN═C═NR (R = i-Pr, Cy, t-Bu) and p-tolN═C═N-p-tol. When they are performed in a strict 1:1 stoichiometry, all four reactions result in silyl addition to the carbodiimide carbon center and formation of the corresponding β-diketiminato magnesium silaamidinate complexes. Although the performance of the reaction of [(BDI)MgSiMe2Ph] with 2 equiv of p-tolylcarbodiimide also results in the formation of a silaamidinate anion, the second equivalent is observed to engage with the nucleophilic γ-methine carbon of the BDI ligand to provide a tripodal diimino-iminoamidate ligand. This behavior is judged to be a consequence of the enhanced electrophilicity of the N-aryl-substituted carbodiimide reagent, a viewpoint supported by a further reaction with the N-isopropyl silaamidinate complex [(BDI)Mg(i-PrN)2CSiMe2Ph]. This latter reaction not only provides an identical diimino-iminoamidate ligand but also results in 2-fold insertion of p-tolN═C═N-p-tol into a Mg-N bond between the magnesium center and the silaamidinate anion.

Diverse Reactivity of a Rhenium(V) Oxo Imido Complex: [2 + 2] Cycloadditions, Chalcogen Metathesis, Oxygen Atom Transfer, and Protic and Hydridic 1,2-Additions.

We present a wide range of reactivity studies focused on the rhenium(V) oxo imido complex (DippN)(O)Re(BDI) (1, Dipp = 2,6-diisopropylphenyl and BDI = N,N'-bis(2,6-diisopropylphenyl)-3,5-dimethyl-β-diketiminate). This complex, which was previously shown to possess a highly polarized Re oxo moiety, has proven to be a potent nucleophile and a valuable precursor to a variety of rare structural motifs in rhenium coordination complexes. For example, the Re oxo moiety of 1 undergoes [2 + 2] cycloadditions with carbodiimides, isocyanates, carbon dioxide, and isothiocyanates at room temperature. In the case of CO2, the cycloadduct with 1 (a carbonate complex) undergoes the facile ejection of CO2, demonstrating that this binding process is reversible. In the case of isothiocyanate, chalcogen metathesis with 1 takes place readily as the inclusion of a second equivalent of substrate in the reaction mixture rapidly yields a dithiocarbamate complex. This metathesis process was extended to the reactivity of 1 with phosphine chalcogenides, leading to the isolation of terminal sulfido imido and selenido imido complexes. Attempts to complete this series and generate the analogous terminal telluride led to the formation of a bidentate tritelluride (Te32-) complex. Triethylphosphine could only undergo oxygen atom transfer (OAT) with 1 under pressing thermal conditions that also led to C-N cleavage of the BDI ligand. In contrast, OAT between 1 and CO or 2,6-xylylisocyanide (XylNC) was found to be much more facile, proceeding within seconds at room temperature. While the addition of excess CO led to a rhenium(III) imido dicarbonyl complex, we found that the addition of 2 equiv of XylNC was necessary to promote OAT, resulting in the isolation of a rare example of a stable metal isocyanate complex. Our experimental observations of CO and XylNC and their OAT reactions with 1 inspired a mechanistic computational study to probe the intermediates and kinetic barriers along these reaction pathways. Finally, we describe 1,2-additions of both protic and hydridic substrates with the Re oxo moiety of 1, which most notably led to the syntheses of an uncommon example of a terminal rhenium hydroxide complex and an oxo-bridged Re-O-Zr hetero-bi-metallic complex that was generated using Schwartz's reagent (Cp2ZrHCl). A brief discussion of a potential alternative route to 1 is also presented.

Phosphinoborane interception at magnesium by borane-assisted phosphine-borane dehydrogenation.

Reactions of B(C6F5)3 with the β-diketiminato (BDI) alkaline-earth phosphidoborane complexes, 1a [(BDI)Ca(H3B·PPh2)] and 1b [(BDI)Mg(H3B·PPh2)]2 (BDI = [HC{C(CH3)N(2,6-iPr-C6H3)}2]-) result in the formation of phosphinodiboronate complexes 4a [(BDI)Ca(η6-toluene){H3B·PPh2·B(C6F5)3}] and 4b [(BDI)Mg{H3B·PPh2·B(C6F5)3}]. Calcium complex 4a is stable in aromatic solvents at room temperature and does not display well-defined onward reactivity at elevated temperatures. Magnesium complex 4b undergoes a room temperature transformation to provide the known hydridoborate derivative 3b [(BDI)Mg{HB(C6F5)3}] and an N,P,N'-ligated species, 5 [{HC(C(CH3)N(2,6-iPr-C6H3))2(H2BPPh2)}Mg{H3B·PPh2·B(C6F5)3}] that results from interception of the putative phosphinoborane, H2B = PPh2, by the BDI ligand backbone following B(C6F5)3-mediated hydride abstraction. NMR spectroscopic investigations were supported by DFT calculations, which suggested a mechanism involving B(C6F5)3 migration and hydride abstraction within the coordination sphere of magnesium. Interception of H2B = PPh2 by B(C6F5)3 is proposed to stabilise this species, whilst activating it towards ligand-centred nucleophilic attack. The significant stabilisation energy calculated for the Ca-π(toluene) interaction in 4a accounts for the contrasting outcomes between the two Ae-elements. The crystal structures of compounds 4a and 5 are presented and discussed.

A computational mechanistic insight into H2 activation and CO2 reduction over β-Diketiminato-ligated group 13 metal complexes

The mechanisms of the cascade H2 activation and CO2 reduction over the β-Diketiminato (BDI)-ligated group 13 metal complexes were studied by the density functional theory (DFT) in the framework of ONIOM method. For the initial H2 activation, the intermolecular 1,4-addition pathway is demonstrated to be kinetically more favorable than the intramolecular 1,2 or 1,4-addition pathway. With the intermolecular Lewis acid-base cooperation catalysis, the heterolytic H⋯H bond cleavage adopts an electron transfer model, which involves the concerted donation from the HH σ bonding orbital to the empty 4pz orbital of the GaIII center, and the backdonation from the π-orbital of the exocyclic alkene in the BDI ligand to the HH σ anti-bonding orbital. Furthermore, it is interesting to note that the simultaneous introduction of the electron-withdrawing group (CF3) on the GaIII center and the electron-donating group (OMe or NMe2) on the C6 position of the BDI ligand is effective for enhancing the reactivity of the BDI-GaIII complex in H2 activation. CO2 might be reduced barrierlessly with the more reactive gallium hydride anion that is generated in H2 activation. For both H2 activation and CO2 reduction processes, the BDI-ligated gallium complexes exert the better catalytic effect than the aluminum analogues.

Low Valent Magnesium Chemistry with a Super Bulky β-Diketiminate Ligand.

The steric bulk of the well-known DIPP BDI ligand (CH[C(CH3 )N-DIPP]2 , DIPP=2,6-diisopropylphenyl) was increased by replacing isopropyl for isopentyl groups. This very bulky DIPeP BDI ligand could not stabilize the radical species (DIPeP BDI)Mg. : reduction of (DIPeP BDI)MgI with Na gave (DIPeP BDI)2 Mg2 with a rather long Mg-Mg bond of 3.0513(8) Å. Addition of TMEDA prior to reduction gave complex (DIPeP BDI)2 Mg2 (C6 H6 ), which could also be obtained as its THF adduct. It is speculated that combination of a bulky spectator ligand and TMEDA prevents dimerization of the intermediate MgI radical, which then reacts with the benzene solvent. Complex (DIPeP BDI)2 Mg2 (C6 H6 ), which formally contains the anti-aromatic anion C6 H6 2- , reacted with tBuOH as a Brønsted base to 1,3- and 1,4-cyclohexadiene and with H2 as a two electron donor to (DIPeP BDI)2 Mg2 H2 and C6 H6 . It also reductively cleaved the C-F bond in fluorobenzene and gave (DIPeP BDI)MgPh, (DIPeP BDI)MgF, and C6 H6 .

Reductions of a Rhenium(III) Terminal Oxo Complex by Isocyanides and Carbon Monoxide

We report on the reductive reactivity of the d4 rhenium(III) oxo olefin complex ORe(η2-DHF)(BDI) (DHF = dihydrofulvalene, BDI = N,N′-bis(2,6-diisopropylphenyl)-2,4-dimethyl-β-diketiminate) with isocyanides, R–NC (R = tBu, 2,6-xylyl), as well as carbon monoxide (CO). These reactions all proceed by an oxygen atom transfer (OAT) to generate rhenium(I) BDI complexes containing 4 equiv of the respective π-acidic reagent. In the case of isocyanides, the products (R–NC)4Re(BDI) (1, R = tBu; 2, R = 2,6-xylyl) were isolated and characterized. While these tetrakis(isocyanide) complexes are stable at room temperature, the tetracarbonyl complex (CO)4Re(BDI) quickly degraded upon formation, leading to demetalation of the BDI ligand. However, inclusion of a strong σ-donor in the reaction of ORe(η2-DHF)(BDI) with CO afforded the tricarbonyl complex fac-(CO)3Re(DMAP)(BDI) (3). In addition to 3, the oxidation product (O)2Re(DMAP)(BDI) (4) was also consistently isolated from this reaction in low yield. We hypothesize compl...

Rh and Ir β-Diiminate Complexes of Boranes, Silanes, Germanes, and Stannanes

Reported here are several new adducts of the type (RBDI)M(HE)2 where RBDI is the β-diiminate ligand [2,6-R2C6H3N═CMe]2CH (R = Me, Et, MeO; M = Rh, Ir; HE = HSiEt3, HGeEt3, HSnnBu3, HBPin). DFT calculations are used to analyze the bonding in these and related Cp* complexes, in particular with respect to the degree of oxidative addition (OA) of the H–E bonds: this increases in the order H2 < HBPin < HSiEt3 ≈ HGeEt3 ≈ HSnnBu3, it proceeds further for Ir than for Rh, and Cp* promotes OA to a larger degree in comparison to the BDI ligand. The first metal–HE dissociation energy is rather sensitive to steric effects and increases in the order CH4 ≪ H2 ≈ HBPin ≈ HSiMe3 ≈ HGeMe3 < HSnMe3, with Ir uniformly binding HE more strongly than Rh by about 10 kcal/mol. M–HE dissociation is the first step of the intramolecular ligand functionalization first reported for (MeBDI)Rh(HSiEt3)2. Such functionalization was not observed for any of the new complexes reported here. On the basis of the idea that stannane dissociation might be prohibitive, we obtained evidence that it is possible to effect such functionalization via generation of a stannane within the coordination sphere of the metal: treatment of (MeBDI)Rh(COE)(N2) with SnMe4 and H2 produced a mixture of (MeBDI)Rh(HSnMe3)2 and its functionalized derivative (MeBDI∧SnHMe2)Rh(HSnMe3) via Sn–C cleavage.

Oxygen Atom Transfer and Intramolecular Nitrene Transfer in a Rhenium β-Diketiminate Complex.

We present two routes to the oxo rhenium complex OReCl2(BDI) (1) (BDI = N,N'-bis(2,6-diisopropylphenyl)-β-diketiminate) and discuss the properties and reactivity of this material. Several adducts of 1 with DMAP (1-DMAP; DMAP = 4-dimethylaminopyridine), isonitriles (1-XylNC; XylNC = 2,6-dimethylphenyl isocyanide), and phosphines (1-PEt3; PEt3 = triethylphosphine) were isolated and characterized. Additionally, to probe the ancillary limitations of the BDI framework in high-valent rhenium complexes, oxygen atom transfer (OAT) reactivity with 1 was pursued. It was found that under thermolysis conditions OAT between 1 and PEt3 was observed by NMR spectroscopy, which indicated the formation of a new species, (ArN)ReCl2(MAD)(PEt3) (2; Ar = 2,6-diisopropylphenyl, MAD = 4-((2,6-diisopropylphenyl)imino)pent-2-enide). A mechanism for the generation of 2 involving nitrene transfer to rhenium from the BDI ligand is proposed. X-ray crystal structures of complexes 1, 1-PEt3, 1-DMAP, and 2 were determined and are discussed in detail.

ChemInform Abstract: Group 5 Chemistry Supported by β‐Diketiminate Ligands

AbstractReview: 195 refs.

ChemInform Abstract: On the Non‐Innocence of “Nacnacs”: Ligand‐Based Reactivity in β‐Diketiminate Supported Coordination Compounds

AbstractReview: 300 refs.

Unusual κ1 coordination of a β-diketiminate ligand in niobium complexes.

Reaction of (BDI)Nb(N(t)Bu)Cl2py with NaCp results in the κ(1)-coordination of the BDI ligand in the complex (κ(1)-N,BDI)CpNb(N(t)Bu)Cl (2). Via chloride abstraction from 2, we develop synthetic routes to structurally analogous cationic and Nb(IV) pseudo-four coordinate complexes where the BDI ligand returns to the κ(2)-coordination mode. We compare these to our previously reported tetrahedral niobium bis(imido) complexes to investigate the effects of the Cp ligand on the properties of Nb-BDI-imido systems. Substitution of the chloride in 2 with a hydride also causes return to bidentate binding of the BDI ligand. The X-ray crystal structures of these complexes have been determined, and the structural parameters reflecting the consequences of the electronic differences are discussed.

Activation of white phosphorus by low-valent group 5 complexes: formation and reactivity of cyclo-P4 inverted sandwich compounds.

We report the synthesis and comprehensive study of the electronic structure of a unique series of dinuclear group 5 cyclo-tetraphosphide inverted sandwich complexes. White phosphorus (P4) reacts with niobium(III) and tantalum(III) β-diketiminate (BDI) tert-butylimido complexes to produce the bridging cyclo-P4 phosphide species {[(BDI)(NtBu)M]2(μ-η3:η3P4)} (1, M = Nb; 2, M = Ta) in fair yields. 1 is alternatively synthesized upon hydrogenolysis of (BDI)Nb(NtBu)Me2 in the presence of P4. The trinuclear side product {[(BDI)NbNtBu]3(μ-P12)} (3) is also identified. Protonation of 1 with [HOEt2][B(C6F5)4] does not occur at the phosphide ring but rather involves the BDI ligand to yield {[(BDI#)Nb(NtBu)]2(μ-η3:η3P4)}[B(C6F5)4]2 (4). The monocation and dication analogues {[(BDI)(NtBu)Nb]2(μ-η3:η3P4)}{B(ArF)4}n (5, n = 1; 6, n = 2) are both synthesized by oxidation of 1 with AgBArF. DFT calculations were used in combination with EPR and UV–visible spectroscopies to probe the nature of the metal–phosphorus bonding.

Generation of low-valent tantalum species by reversible C-H activation in a cyclometallated tantalum hydride complex.

The cyclometallated tantalum(v) hydride complex {ArNC(Me)CHC(Me)N[2-(CHMeCH2)-6-(i)Pr-C6H3]}Ta(N(t)Bu)H (2) was prepared from hydrogenolysis of (BDI)TaN(t)BuMe2 (BDI = N,N'-diaryl-β-diketiminate, aryl = 2,6-(i)Pr2-C6H3). Based on mechanistic studies, formation of 2 likely proceeds through a dihydride intermediate generated from successive σ-bond metathesis steps. Compound 2 was found to undergo reductive elimination under certain conditions to form trivalent tantalum species. Coordination of DMAP to 2, followed by gentle heating under H2, gives (MAD)Ta(N(t)Bu)(NAr)(DMAP), which is produced through reductive C-N bond cleavage of the BDI ligand in a Ta(iii) intermediate. Ta(iii) dicarbonyl derivatives have been accessed by either introducing CO atmosphere to the DMAP adduct of 2 at room temperature, or by directly adding CO to 2 at low temperature.

Group 14 Metal Terminal Phosphides: Correlating Structure with |JMP|

A series of heavier group 14 element, terminal phosphide complexes, M(BDI)(PR(2)) (M = Ge, Sn, Pb; BDI = CH{(CH(3))CN-2,6-iPr(2)C(6)H(3)}(2); R = Ph, Cy, SiMe(3)) have been synthesized. Two different conformations (endo and exo) are observed in the solid-state; the complexes with an endo conformation have a planar coordination geometry at phosphorus (M = Ge, Sn; R = SiMe(3)) whereas the complexes possessing an exo conformation have a pyramidal geometry at phosphorus. Solution-state NMR studies reveal through-space scalar coupling between the tin and the isopropyl groups on the N-aryl moiety of the BDI ligand, with endo and exo exhibiting different J(SnC) values. The magnitudes of the tin-phosphorus and lead-phosphorus coupling constants, |J(SnP)| and |J(PbP)|, differ significantly depending upon the hybridization of the phosphorus atom. For Sn(BDI)(P{SiMe(3)}(2)), |J(SnP)| is the largest reported in the literature, surpassing values attributed to compounds with tin-phosphorus multiple-bonds. Low temperature NMR studies of Pb(BDI)(P{SiMe(3)}(2)) show two species with vastly different |J(PbP)| values, interpreted as belonging to the endo and exo conformations, with sp(2)- and sp(3)-hybridized phosphorus, respectively.

Drug-Initiated, Controlled Ring-Opening Polymerization for the Synthesis of Polymer-Drug Conjugates.

Paclitaxel, a polyol chemotherapeutic agent, was covalently conjugated through its 2'-OH to polylactide with 100% regioselectivity via controlled polymerization of lactide mediated by paclitaxel/(BDI-II)ZnN(TMS)(2) (BDI-II = 2-((2,6-diisopropylphenyl)amino)-4-((2,6-diisopropylphenyl)imino)-2-pentene). The steric bulk of the substituents on the N-aryl groups of the BDI ligand drastically affected the regiochemistry of coordination of the metal catalysts to paclitaxel and the subsequent ring-opening polymerization of lactide. The drug-initiated, controlled polymerization of lactide was extended, again with 100% regioselectivity, to docetaxel, a chemotherapeutic agent that is even more structurally complex than paclitaxel. Regioselective incorporation of paclitaxel (or docetaxel) to other biopolymers (i.e., poly(δ-valerolactone), poly(trimethylene carbonate), and poly(ε-caprolactone)), was also achieved through drug/(BDI-II)ZnN(TMS)(2)-mediated controlled polymerization. These drug-polylactide conjugates with precisely controlled structures are expected to be excellent building blocks for drug delivery, coating, and controlled-release applications.

Ring-Opening Polymerization-Mediated Controlled Formulation of Polylactide−Drug Nanoparticles

We report here a unique method for formulating doxorubicin-polylactide (Doxo-PLA) conjugate nanoparticles, known as nanoconjugates (NCs), through Doxo/(BDI)ZnN(TMS)(2)-mediated [(BDI) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene], chemo- and regioselective polymerizations of lactide (LA) followed by nanoprecipitation. When Doxo/(BDI)ZnN(TMS)(2) was mixed with 1-pyrenemethanol (Pyr-OH) and 1-pyrenemethylamine (Pyr-NH(2)) and the mixture was utilized for the polymerization of LA, remarkable chemoselectivity was observed. Pyr-OH was completely consumed and covalently linked to the terminus of the PLA, whereas the Pyr-NH(2) remained intact in the polymerization solution. When Doxo was used as the initiator to polymerize LA in the presence of (BDI)ZnN(TMS)(2), the polymerization was complete within hours, with nearly 100% Doxo-loading efficiency and 100% LA conversion. Doxo loading as high as 27% could be achieved at a LA/Doxo ratio of 10. Both the steric bulk of the chelating ligand and the metal catalyst had dramatic effects on the regioselectivity during the initiation step. When Doxo/(BDI)ZnN(TMS)(2) was mixed with succinic anhydride (SA) to mimic the initiation of Doxo/(BDI)ZnN(TMS)(2)-mediated LA polymerization, Doxo-14-succinic ester (Doxo-SE) was the predominate product. When the steric bulk of BDI was reduced or when the BDI ligand was removed, significant amounts of Doxo-4',14-bis-succinic ester (Doxo-2SE) and Doxo-4',9,14-trisuccinic ester (Doxo-3SE) were formed. The use of (BDI)MgN(TMS)(2) in such a reaction also resulted in reduced regioselectivity and formation of both Doxo-SE and Doxo-2SE. Doxo/(BDI)ZnN(TMS)(2)-mediated LA polymerizations yielded Doxo-PLA conjugates with well-controlled molecular weights and polydispersities (as low as 1.02). The nanoprecipitation of Doxo-PLA formed NCs less than 150 nm in size with narrow particle size distributions. The sustained release of Doxo from Doxo-PLA NCs was achieved without a burst release. This method may have widespread utility for controlled conjugation of hydroxyl-containing agents to polyesters and formation of corresponding nanoparticles.