Borane Group Research Articles

Chiral organoborane Lewis pairs derived from pyridylferrocene.

In an effort to develop a new class of redox-active chiral Lewis pairs, pyridine and borane moieties with different steric and electronic properties were introduced onto a planar chiral 1,2-disubstituted ferrocene framework. Metathesis of lithiated, stannylated, or mercuriated pyridylferrocenes with boron halides afforded (pR)-2-[bis(pentafluorophenyl)boryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene (4-Pf), (pR)-2-[dimesitylboryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene (4-Mes), (pS)-2-(bis(pentafluorophenyl)boryl)-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Pf), or (pS)-2-[dimesitylboryl]-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Mes). The borylated products were analyzed by multinuclear NMR spectroscopy, HRMS, and single-crystal X-ray diffraction. Chiral HPLC and optical-rotation measurements were employed to assess the stereoselectivity of the borylation process and to establish the correct stereochemical assignments. The strength of the B-N interactions were investigated in solution and in the solid state. Compounds 4-Pf and 4-Mes formed robust 'closed' B-N heterocyclic systems that proved to be perfectly stable to air and moisture, whereas 5-Pf established a dynamic equilibrium, in which the B-N heterocycle was observed exclusively at room temperature, but opened up at high temperature according to (19)F NMR exchange spectroscopy data. As a consequence, 5-Pf reacted readily with a molecule of water to generate a ring-opened pyridinium borate. The combination of bulky borane and bulky pyridyl groups in 5-Mes led to a completely 'open' frustrated Lewis pair system with uncomplexed pyridine and borane groups, even at room temperature. Electrochemical studies were performed and the effect of preparative ferrocene oxidation on the structural features was also explored.

Inhibition of hepatitis C viral RNA-dependent RNA polymerase by α-P-boranophosphate nucleotides: Exploring a potential strategy for mechanism-based HCV drug design

Improved treatments for chronic HCV infections remain a challenge, and new chemical strategies are needed to expand the current paradigm. The HCV RNA polymerase (RdRP) has been a target for antiviral development. For the first time we show that the boranophosphate (BP) modification increases the substrate efficiency of ATP analogs into HCV NS5BΔ55 RdRP-catalyzed RNA. Boranophosphate nucleotides contain a borane (BH3) group substituted for a non-bridging phosphoryl oxygen of a normal phosphate group, resulting in a class of modified isoelectronic DNA and RNA mimics capable of modulating the reading and writing of genetic information. We determine that HCV NS5BΔ55, being a stereospecific enzyme, incorporates the Rp isomer of both ATPαB and the two boranophosphate analogs: 2′-O-methyladenosine 5′-(α-P-borano) triphosphate (2′-OMe ATPαB, 5a) and 3′-deoxyadenosine 5′-(α-P-borano) triphosphate (3′-dATPαB, 5b). The Rp diastereomer of ATPαB (6), having no ribose modifications, was found to be a slightly better substrate than natural ATP, showing a 42% decrease in the apparent Michaelis–Menten constant (Km). The IC50 of both 2′-O-Me and 3′-deoxy ATP was decreased with the boranophosphate modification up to 16-fold. This “borano effect” was further confirmed by determining the steady-state inhibitory constant (Ki), showing a comparable potency shift (21-fold). These experiments also indicate that the boranophosphate analogs 5a and 5b inhibit HCV NS5B through a competitive mode of inhibition. This evidence, together with previous crystal structure data, further supports the idea that HCV NS5B (in a similar manner to HIV-1 RT) discriminates against the 3′-deoxy modification via lost interactions between the 3′-OH on the ribose and the active site residues, or lost intramolecular hydrogen bonding interactions between the 3′-OH and the pyrophosphate leaving group during phosphoryl transfer. To our knowledge, these data represent the first time a phosphate modified NTP has been studied as a substrate for HCV NS5B RdRP.

Remarkable coordination behavior of alkyl isocyanides toward unsaturated vicinal frustrated P/B Lewis pairs

The conjugated frustrated phosphane/borane Lewis pairs formed by 1,1-carboboration of a substituted diphenylphosphino acetylene, undergo a synergistic 1,1-addition reaction to n-butyl isocyanide with formation of new B–C and P–C bonds to the former isonitrile carbon atom. Using tert-butyl isocyanide dynamic behaviour between the isocyanide–[B] adduct and the 1,1-addition product formation was observed in solution. The different modes of isocyanide binding to the FLPs in the solid state were characterized using X-ray crystal structure analyses and comprehensive 11B and 31P solid-state magic-angle-spinning (MAS-) NMR experiments. The free FLP, the Lewis adduct at the borane group, and the cyclic product resulting from isocyanide addition to both reaction centers, can be differentiated via11B and 31P isotropic chemical shifts, 11B nuclear electric quadrupole coupling constants, isotropic indirect 11B–31P spin–spin coupling constants, and 11B⋯31P internuclear distances measured by rotational echo double resonance.

Exploring the fate of the tris(pentafluorophenyl)borane radical anion in weakly coordinating solvents

We report a kinetic and mechanistic study into the one-electron reduction of the archetypal Lewis acid tris(pentafluorophenyl)borane, B(C(6)F(5))(3), in dichloromethane and 1,2-difluorobenzene. Electrochemical experiments, combined with digital simulations, DFT computational studies and multinuclear NMR analysis allow us to obtain thermodynamic, kinetic and mechanistic information relating to the redox activity of B(C(6)F(5))(3). We show that tris(pentafluorophenyl)borane undergoes a quasi-reversible one-electron reduction followed by rapid chemical decomposition of the B(C(6)F(5))(3)˙(-) radical anion intermediate via a solvolytic radical pathway. The reaction products form various four-coordinate borates of which [B(C(6)F(5))(4)](-) is a very minor product. The rate of the follow-up chemical step has a pseudo-first order rate constant of the order of 6 s(-1). This value is three orders of magnitude larger than that found in previous studies performed in the donor solvent, tetrahydrofuran. The standard reduction potential of B(C(6)F(5))(3) is reported for the first time as -1.79 ± 0.1 V and -1.65 ± 0.1 V vs. ferrocene/ferrocenium in dichloromethane and 1,2-difluorobenzene respectively.

Molecular modeling of the lipase-catalyzed hydrolysis of acetoxymethyl(i-propoxy)phenylphosphine oxide and its P-borane analogue

The molecular modeling of the CAL-B-promoted hydrolysis reactions of acetoxymethyl(i-propoxy)phenylphosphine oxide and its P-borane analogue, acetoxymethyl(i-propoxy)-phenylphosphine P-borane, confirms that the reactions proceed with the same stereochemistry and in both cases the (S)-enantiomers are preferentially transformed by the enzyme. Molecular mechanics calculations show that the main reason for the particular stereoselectivity of the substrates is the steric effect of the phenyl group which causes a remarkable hindrance when placed inside the active site. The replacement of the oxygen by a borane group at the phosphorus stereogenic center does not nullify the stereorecognition by the enzyme, although for the P-borane a lower stereoselectivity is observed. The latter is explained in terms of a smaller energy difference between complexes of CAL-B and particular enantiomers of the P-borane in comparison with those of the phosphine oxide, resulting from the steric effect of the BH3 group. The results helped to revise the previously published erroneous conclusions concerning absolute configuration of the phosphine–borane complex.

N-Heterocyclic carbene-borane radicals as efficient initiating species of photopolymerization reactions under air

Eight N-heterocyclic carbene-boranes (NHC-boranes) are proposed as new efficient co-initiators for acrylate photopolymerization reactions. They are particularly interesting in aerated conditions, where they help overcome the classical oxygen inhibition. The carbene boryl radicals that are the initiating species have been characterized by their transient absorption spectra obtained in laser flash photolysis (LFP) experiments. Rate constants for the generation of the carbene boryl radicals by hydrogen abstraction with t-butoxyl radical and triplet benzophenone as well as the reactions with oxygen, electron rich and electron poor alkenes, two alkyl halides (CHCl3 and iodopropane) and diphenyliodonium hexafluorophosphate have been measured. The reactivity of N-heterocyclic carbene borane radicals is clearly affected by the NHC substituent.

Two‐Dimensional Chromatographic Analysis of Polystyrene‐block‐poly(methyl methacrylate) Copolymers Synthesized by Selective Oxidation of Polystrene‐9‐borabicyclo[3.3.1]nonane

AbstractSummary: The preparation of polystyrene block methyl methacrylate copolymers (PS‐b‐PMMA) is described. The polystyrene segment was prepared by anionic polymerization and the methylmethacrylate segment was prepared via free radical autoxidation of a borane agent attached to the styrene chain.1 The chemistry involves a transformation of the anionic polymerization process to borane chemistry by firstly producing polystyrene with chain end unsaturated alkyl functional groups prepared using a n‐butyllithium initiator and termination with allylchlorodimethylsilane. Secondly, the unsaturated macroinitiator end was hydroborated by 9‐borabicyclo[3.3.1]nonane (9‐BBN) to produce a borane terminated PS. Thirdly, the borane group at the chain end was selectively oxidized and converted to polymeric radicals in the presence of methyl methacrylate which then initiated radical polymerization to produce block copolymers. The polymer obtained was characterized using several chromatographic techniques including LC‐CC (liquid chromatography under critical conditions) for the polystyrene segments and two‐dimensional chromatography with LC‐CC in the first dimension and SEC in the second. The results show that block formation was successful although significant homopolymerization of methyl methacrylate is also obtained.

ChemInform Abstract: The Diastereoselective and Enantioselective Substitution Reactions of an Isoindoline-Borane Complex.

The alkylation of N-methylisoindoline–borane complex, using nBuLi in THF is diastereoselective, the substitution occurring predominantly syn to the borane group. Use of the sBuLi–sparteine reagent mixture in Et2O changes the diastereoselectivity observed and enables the reaction to be conducted enantioselectively, giving the chiral isoindoline–borane complexes in up to 89% ee. The relative and absolute configurations of the chiral products were established by X-ray structure determinations and NMR studies. The new asymmetric process is shown to be an enantioselective deprotonation reaction, and the intermediate organolithium is shown to be epimerisable.

Diversity of Metal−Ligand Interactions in Halide (X = I, Br, Cl, F) and Halide-Free Ambiphilic Ligand Rhodium Complexes

Reaction of the neutral ambiphilic ligand 2,7-di-tert-butyl-5-diphenylboryl-4-diphenylphosphino-9,9-dimethylthioxanthene (TXPB) with [{Rh(mu-Cl)(CO)(2)}(2)] yields [RhCl(CO)(TXPB)] (1) (Emslie et al. Organometallics 2006, 25, 5835). Complex 1 is square planar with the TXPB ligand bound to rhodium via the phosphine and thioether donors (these are features common to complexes 2-5, vide infra). Treatment of 1 with Me(3)SiBr and Me(3)SiI allowed for halide substitution to afford [RhBr(CO)(TXPB)] (2) and [RhI(CO)(TXPB)] (3), respectively. The halide co-ligands in complexes 1 and 2 form a strong bridging interaction between rhodium and the borane group in TXPB. The presence of stronger borane-halide coordination in 1 is clearly illustrated by an (11)B NMR chemical shift of 12 ppm versus 27 ppm in 2. In contrast, the iodide ligand in 3 forms only a weak bridging interaction to boron, leading to a B...I distance of 3.125(7) A, and an (11)B NMR chemical shift of 56 ppm (versus 69 ppm for free TXPB). A lower carbonyl stretching frequency in 3 (2002 cm(-1)) versus 1 or 2 (2008 and 2013 cm(-1), respectively) could be attributed to weakening of the Rh-X bond in 1 and 2 as a consequence of halide-borane coordination and/or a shorter Rh-S bond in complex 3. [Rh(CO)(TXPB-F)] (4) and the halide-free cation [Rh(CO)(TXPB)][PF(6)] (5) were accessed by reaction of 1 with [NMe(4)]F and Tl[PF(6)], respectively. Complex 4 is zwitterionic with fluoride bound to boron [(11)B NMR delta 4 ppm; B-F = 1.445(6) A; Rh...F = 3.261(3) A] and an eta(2)-interaction between the cationic rhodium center and the ipso- and ortho-carbon atoms of a B-phenyl ring in TXPB-F. By contrast, rhodium in 5 engages in an eta(2)-interaction with boron and the ipso-carbon of one B-phenyl ring; Rh-B and Rh-C(ipso) bond lengths in 5 are 2.557(3) and 2.362(2) A, respectively. The long Rh-B distance and an (11)B NMR chemical shift of 57 ppm are consistent with only a weak Rh-B interaction in 5, and a CO stretching frequency of 2028 cm(-1) (Nujol), versus 2004-2013 cm(-1) for complexes 1-4, is indicative of greatly reduced electron density in 5, relative to 1-4.

EPR Studies of the Generation, Structure, and Reactivity of N-Heterocyclic Carbene Borane Radicals

N-Heterocyclic carbene boranes (NHC-boranes) are a new "clean" class of reagents suitable for reductive radical chain transformations. Their structures are well suited for their reactivity to be tuned by inclusion of different NHC ring units and by appropriate placement of diverse substituents. EPR spectra were obtained for the boron-centered radicals generated on removal of one of the BH(3) hydrogen atoms. This spectroscopic data, coupled with DFT computations, demonstrated that the NHC-BH(2)* radicals are planar pi-delocalized species. tert-Butoxyl radicals abstracted hydrogen atoms from NHC-boranes more than 3 orders of magnitude faster than did C-centered radicals, although the rate decreased markedly for sterically shielded NHC-BH(3) centers. Combinations of two NHC-boryl radicals afforded 1,2-bis-NHC-diboranes at rates which also depended strongly on steric shielding. The termination rate increased to the diffusion-controlled limit for sterically unhindered NHC-boryls. Bromine atoms were rapidly transferred to imidazole-based NHC-boryl radicals from alkyl, allyl, and benzyl bromides. Chlorine-atom abstraction was, however, much less efficient and only observed for sterically unhindered NHC-boryls reacting with allylic and benzylic chlorides. For an NHC-borane containing a bulky thexyl substituent at boron, the tertiary H atom of the thexyl group was selectively removed. The resulting beta-boron-containing alkyl radical rapidly underwent beta scission of the B-C bond with production of an NHC-boryl radical and an alkene.

Edging In with Iron

Chemistry Hydroboration is widely used in organic chemistry to append a borane and a hydrogen atom to respective carbons at either end of a double bond; the borane group can then be efficiently replaced to form a range of compounds such as alcohols. Wu et al. now show that an iron catalyst facilitates a variation on this reaction in 1,3-dienes: hydrocarbon derivatives with two double bonds separated by a single bond (C=C–C=C). Instead of adding boron and hydrogen to adjacent carbons, the reaction proceeds to add them at opposite edges of the four-carbon sequence, concomitantly creating a double bond between the central carbons. The catalyst forms in situ through reduction of an iminopyridine iron(II) complex by magnesium. In substrates substituted at one of the central carbons in the diene framework, the reaction is highly selective for the E product geometry about the newly formed double bond, complementing a previously developed palladium-catalyzed variant of this reaction class that favors the opposite stereochemistry. Varying the imine substituent on the ligand also allows the authors to modulate which end carbon receives the boron. J. Am. Chem. Soc. 131 , 10.1021/ja9048493 (2009).

Microwave Spectrum, Structure, Barrier to Internal Rotation, and Dipole Moment of the Aziridine−Borane Complex (C2H5N−BH3)

The microwave spectrum of the aziridine-borane complex (C(2)H(5)N-BH(3)) has been investigated by microwave spectroscopy in the 18-80 GHz spectral region. The spectra of the ground vibrational state and three vibrationally excited states have been assigned, and the vibrational frequencies of these states have been determined. The complex was found to have a symmetry plane (C(s) symmetry) formed by the N-B bond and the bisector of the aziridine ring. The dative N-B bond is found to be as short as 161.5 pm in MP2/aug-cc-pVTZ calculations. The MP2 structure of the aziridine ring of this complex is nearly the same as that in the substitution structure of aziridine. Complex formation therefore appears to have little influence on this moiety. The dipole moment was determined to be mu(a) = 17.72(11), mu(b) = 0.0 (by symmetry), mu(c) = 5.70(8), and mu(tot) = 18.62(11) x 10(-30) C m [5.581(34) D]. The barrier to internal rotation of the borane group was determined to be 12.1(3) kJ/mol using the microwave splitting method. The microwave investigation has been augmented by high-level quantum chemical calculations at the MP2/aug-cc-pVTZ and B3LYP/6-311++G** levels of theory. There is generally good agreement between the experimental results and quantum chemical predictions.

Neutron Powder Diffraction and Molecular Simulation Study of the Structural Evolution of Ammonia Borane from 15 to 340 K

The structural behavior of (11)B-, (2)H-enriched ammonia borane, ND(3)(11)BD(3), over the temperature range from 15 to 340 K was investigated using a combination of neutron powder diffraction and ab initio molecular dynamics simulations. In the low temperature orthorhombic phase, the progressive displacement of the borane group under the amine group was observed leading to the alignment of the B-N bond near parallel to the c-axis. The orthorhombic to tetragonal structural phase transition at 225 K is marked by dramatic change in the dynamics of both the amine and borane group. The resulting hydrogen disorder is problematic to extract from the metrics provided by Rietveld refinement but is readily apparent in molecular dynamics simulation and in difference Fourier transform maps. At the phase transition, Rietveld refinement does indicate a disruption of one of two dihydrogen bonds that link adjacent ammonia borane molecules. Metrics determined by Rietveld refinement are in excellent agreement with those determined from molecular simulation. This study highlights the valuable insights added by coupled experimental and computational studies.

Quasielastic neutron scattering of –NH 3 and –BH 3 rotational dynamics in orthorhombic ammonia borane

Energy barriers for rotation of –NH 3 and –BH 3 in the orthorhombic phase of ammonia borane, NH 3BH 3, were determined using quasielastic neutron scattering (QENS). QENS confirms the 3-site jump model of rotational diffusion and yields barrier heights of 23.6 ± 1.0 kJ/mol and 14.8 ± 0.4 kJ/mol for the borane and amine groups, respectively, which are comparable to barrier heights determined by recent 2H and 15N NMR studies suggesting no significant isotope effect on rotational motion in the orthorhombic phase of ammonia borane.

In Vitro Suppression of K65R Reverse Transcriptase-Mediated Tenofovir- and Adefovir-5′-Diphosphate Resistance Conferred by the Boranophosphonate Derivatives

9-[2-(Boranophosphonomethoxy)ethyl]adenine diphosphate (BH(3)-PMEApp) and (R)-9-[2-(boranophosphonomethoxy)propyl]adenine diphosphate (BH(3)-PMPApp), described here, represent the first nucleoside phosphonates modified on their alpha-phosphates that act as efficient substrates for the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). These analogues were synthesized and evaluated for their in vitro activity against wild-type (WT), K65R, and R72A RTs. BH(3)-PMEApp and BH(3)-PMPApp exhibit the same inhibition properties as their nonborane analogues on WT RT. However, K65R RT was found hypersensitive to BH(3)-PMEApp and as sensitive as WT RT to BH(3)-PMPApp. Moreover, the presence of the borane group restores incorporation of the analogue by R72A HIV RT, the latter being nearly inactive with regular nucleotides. The BH(3)-mediated suppression of HIV-1 RT resistance, formerly described with nucleoside 5'-(alpha-p-borano)-triphosphate analogues, is thus also conserved at the phosphonate level. The present results show that an alpha-phosphate modification is also possible and interesting for phosphonate analogues, a result that might find application in the search for a means to control HIV RT-mediated drug resistance.

Preparation of polypropylene/montmorillonite nanocomposites by intercalative polymerization: Effect of in situ polymer matrix functionalization on the stability of the nanocomposite structure

The copolymerization of propylene and 5-hexenyl-9-borabicyclo[3.3.1]nonane (5-hexenyl-9-BBN) has been conducted with an MgCl2/TiCl4 catalyst intercalated in an organically modified montmorillonite (OMMT) with triethylaluminum (AlEt3) cocatalyst and diphenyldimethoxysilane (DDS) external donor. This polymerization process simultaneously results in both the exfoliation of MMT layers to realize the preparation of polypropylene (PP)/MMT nanocomposites and the implantation of reactive borane groups in the formed PP matrix. The polymer-borne borane groups have been able to undergo an efficient hydrolysis process under very mild reaction conditions (40°C, 3 h, in THF), introducing hydroxy groups into PP without sacrificing the polymerization-formed nanocomposite structure (the exfoliation of MMT). The resultant hydroxyl-functionalized PP/MMT nanocomposites exhibit enhanced structural stability against processing compared with those based on unfunctionalized PP matrix.

Synthesis, in Vitro Antiviral Evaluation, and Stability Studies of Novel α-Borano-Nucleotide Analogues of 9-[2-(Phosphonomethoxy)ethyl]adenine and (R)-9-[2-(Phosphonomethoxy)propyl]adenine

We describe here the synthesis of 9-[2-(boranophosphonomethoxy)ethyl]adenine (6a) and (R)-9-[2-(boranophosphonomethoxy)propyl]adenine (6b), the first alpha-boranophosphonate nucleosides in which a borane (BH3) group substitutes one nonbridging oxygen atom of the alpha-phosphonate moiety. H-phosphinates 5a and 5b and alpha-boranophosphonates 6a and 6b were evaluated for their in vitro activity against human immunodeficiency virus (HIV) infected cells and against a panel of DNA or RNA viruses. Compounds 5a, 5b, 6a, and 6b exhibited no significant antiviral activity in vitro and cytotoxicity. To measure the chemical and enzymatic stabilities of the target compounds 6a and 6b, kinetic data of decomposition for derivatives 5a, 5b, 6a, 6b, and standard compounds were studied at 37 degrees C in several media. The alpha-boranophosphonates 6a and 6b were metabolized in culture medium into H-phosphinates 5a and 5b, with half-live values of 5.3 h for 6a and 1.3 h for 6b.

Synthesis of Novel α‐Aminoboronate Complexes of Aminoboranes and Aminocyanoboranes

AbstractTertiary amines activated either by borane (BH3) or cyanoborane (BH2CN) groups were α‐C lithiated with sBuLi (2 equiv.) and then treated with 2‐isopropoxy‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane to produce the α‐aminoboronate complexes of aminoboranes and aminocyanoboranes 2–7 in 70–85 % yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Stabilization of a Dialkylstannylene by Unusual B−H···Sn γ-Agostic-Type Interactions. A Structural, Spectroscopic, and DFT Study

The reaction between SnCl2 and the lithium salt [[{nPr2P(BH3)}(Me3Si)CCH2]Li(THF)2]2 yields the cyclic dialkylstannylene [{nPr2P(BH3)}(Me3Si)CCH2]2Sn (6) as a 1:1 mixture of rac and meso diastereomers. Fractional crystallization from n-hexane gives samples of pure rac-6 and meso-6 which have been studied by X-ray crystallography, UV/visible, infrared, and multi-element NMR spectroscopy. In the solid state, rac-6 exhibits two short agostic-type B−H···Sn contacts, one to each BH3 group, whereas meso-6, in which both BH3 groups lie on the same side of the heterocycle, exhibits a single B−H···Sn contact. Multi-element and variable-temperature NMR spectroscopy suggests that these contacts persist in solution, resulting in unusual 119Sn chemical shifts of 587 and 787 ppm for the rac and meso diastereomers, respectively, significantly upfield in comparison to other dialkylstannylenes. Variable-temperature 1H, 31P{1H}, and 11B{1H} NMR studies reveal dynamic equilibria for the meso diastereomer involving competitive binding of the two BH3 groups to the electron-deficient tin center and restricted rotation about the P−C bond of the free phosphine−borane group. DFT studies confirm that the B−H···Sn contacts are an integral part of the structures; the HOMO and LUMO of both stereoisomers are comprised of an orbital of essentially 5s character on tin and an orbital of predominantly 5p character on tin perpendicular to the plane of the heterocycle, respectively. There is significant donation of electron density from the B−H σ-bonds to the vacant 5p orbital on tin; these B−H···Sn interactions stabilize the electron-deficient Sn(II) center by 30 kcal mol-1 for meso-6 and 40 kcal mol-1 for rac-6.

Convenient synthesis of nucleoside borane diphosphate analogues: deoxy- and ribonucleoside 5'-P(alpha)-boranodiphosphates.

The nucleoside boranophosphates, having one of the nonbridging phosphate oxygens substituted with a borane (BH(3)) group, have shown potential therapeutical applications as aptamers, antisense agents, and antiviral prodrugs. An oxathiaphospholane approach, which does not require exocyclic amine protection of the nucleobase, has been successfully developed to efficiently synthesize 5'-P(alpha)-boranodiphosphates of 2'-deoxythymidine, adenosine, guanosine, and uridine. The approach involves a key intermediate, the borane complex of nucleoside 5'-O-1,3,2-oxathiaphospholane 16, that undergoes a ring-opening reaction catalyzed by 1,4-diazabicyclo[5.4.0]-undec-7-ene to form the protected nucleoside 5'-P(alpha)-boranodiphosphate 18. Treatment of 18 with ammonium hydroxide yielded diastereoisomeric mixtures of nucleoside 5'-P(alpha)-boranodiphosphates 5. This oxathiaphospholane approach ensures the availability of nucleoside 5'-P(alpha)-boranodiphosphate analogues needed for antiviral drug research.