Flow chemistry-enabled studies of rhodium-catalyzed hydroformylation reactions.

We present an automated microscale flow chemistry platform for rapid performance evaluation of continuous and discrete reaction parameters in homogeneous hydroformylation reactions. We demonstrate the versatility of the developed microfluidic platform through a systematic study of the effects of a library of phosphine-based ligands on catalytic activity and regioselectivity.

Tuning the Porphyrin Building Block in Self-Assembled Cages for Branched-Selective Hydroformylation of Propene.

Unprecedented regioselectivity to the branched aldehyde product in the hydroformylation of propene was attained on embedding a rhodium complex in supramolecular assembly L2, formed by coordination-driven self-assembly of tris(meta-pyridyl)phosphine and zinc(II) porpholactone. The design of cage L2 is based on the ligand-template approach, in which the ligand acts as a template for cage formation. Previously, first-generation cage L1, in which zinc(II) porphyrin units were utilized instead of porpholactones, was reported. Binding studies demonstrate that the association constant for the formation of second-generation cage L2 is nearly an order of magnitude higher than that of L1. This strengthened binding allows cage L2 to remain intact in polar and industrially relevant solvents. As a consequence, the unprecedented regioselectivity for branched aldehyde products can be maintained in polar and coordinating solvents by using the second-generation assembly.

Grade 2 spondylolisthesis at L4-5 treated by XLIF: safety and midterm results in the "worst case scenario".

UNLABELLED: Spondylolisthesis is one of the most common indications for spinal surgery. However, no one approach has been proven to be more effective in treating spondylolisthesis. Recent advances in minimally invasive spine technology have allowed for different approaches to be applied to this indication, notably extreme lateral interbody fusion (XLIF). The risk, however, of using XLIF in treating grade II spondylolisthesis is the ventral position of the lumbar plexus, particularly at L4-5. OBJECTIVE: This study reports the safety and midterm clinical and radiographic outcomes of patients with grade II lumbar spondylolisthesis treated with XLIF. METHODS: 63 patients with grade II spondylolisthesis and spinal stenosis were treated with XLIF and were available for 12-month followup. Of those, 61 (97%) were treated at L4-5. Clinical (VAS, complications, and reoperation rate) and radiographic (anterolisthesis, disk height, and fusion) parameters were assessed. STUDY DESIGN: Data were collected via a prospective registry and analyzed retrospectively. RESULTS: Sixty-three patients were available for evaluations at least one year postoperatively. Average pain (visual analog scale) decreased from a score of 8.7 at baseline to 2.2 at 12 months postoperatively. Average anterior slippage was reduced by 73% and was well maintained. Average disk height (4.6 mm pre-op and 9.0 mm post-op) nearly doubled after surgery. Slight settling (average 1.3 mm) occurred over the twelve-month follow-up period. There were no neural injuries and no nonunions noted. CONCLUSIONS: XLIF is a safe and effective minimally invasive treatment alternative for grade II spondylolisthesis. Real-time neurological monitoring and attention to technique are mandatory.

Economics of less invasive spinal surgery: an analysis of hospital cost differences between open and minimally invasive instrumented spinal fusion procedures during the perioperative period.

BACKGROUND: There is great debate about the costs and benefits of technology-driven medical interventions such as instrumented lumbar fusion. With most analyses using charge data, the actual costs incurred by medical institutions performing these procedures are not well understood. The object of the current study was to examine the differences in hospital operating costs between open and minimally invasive spine surgery (MIS) during the perioperative period. METHODS: Data were collected in the form of a prospective registry from a community hospital after specific Institutional Review Board approval was obtained. The analysis included consecutive adult patients being surgically treated for degenerative conditions of the lumbar spine, with either an MIS or open approach for two-level instrumented lumbar fusion. Patient outcomes and costs were collected for the perioperative period. Hospital operating costs were grouped by hospitalization/operative procedure, transfusions, reoperations, and residual events (health care interactions). RESULTS: One hundred and one open posterior lumbar interbody fusion (Open group) and 109 MIS patients were treated primarily for stenosis coupled with instability (39.6% and 59.6%, respectively). Mean total hospital costs were $27,055.53 for the Open group and $24,320.16 for the MIS group. This represents a statistically significant cost savings of $2,825.37 (10.4% [95% confidence interval: $522.51-$5,128.23]) when utilizing MIS over traditional Open techniques. Additionally, residual events, complications, and blood transfusions were significantly more frequent in the Open group, compared to the MIS group. CONCLUSIONS/LEVEL OF EVIDENCE: Utilizing minimally invasive techniques for instrumented spinal fusion results in decreased hospital operating costs compared to similar open procedures in the early perioperative period. Additionally, patient benefits of minimally invasive techniques include significantly less blood loss, shorter hospital stays, lower complication rate, and a lower number of residual events. Long-term outcome comparisons are needed to evaluate the efficacy of the two treatments. LEVEL OF EVIDENCE: III CLINICAL RELEVANCE: This work represents a true cost-of-operating comparison between open and MIS approaches for lumbar spine fusion, which has relevance to surgeons, hospitals and payers in medical decision-making.

Clinical and radiographic outcomes of extreme lateral approach to interbody fusion with ß-tricalcium phosphate and hydroxyapatite composite for lumbar degenerative conditions.

BACKGROUND: Historically, iliac crest bone graft has been used as the graft of choice for lumbar spine fusion procedures. Because fusion techniques have become less invasive, the demand for minimally disruptive grafting options has increased. This prospective study was performed to assess clinical and radiographic outcomes of patients treated with an iliac crest bone graft alternative and lateral lumbar interbody fusion. METHODS: Fifty degenerative lumbar patients were treated with the extreme lateral approach to interbody fusion and a ß-tricalcium phosphate-hydroxyapatite graft with bone marrow aspirate (BMA) at 1 or 2 adjacent levels. BMA was collected from the iliac crest with a bone aspiration needle and applied to the FormaGraft (NuVasive, Inc., San Diego, California) in a 1:1 ratio. Radiolucent cages were filled with FormaGraft strips, granules, or blocks and implanted in a standard fashion. Clinical data were collected at baseline, 6 weeks, and 3, 6, and 12 months and included visual analog scale, Oswestry Disability Index, and Short Form 36 patient-reported assessments. Fusion assessments were made from neutral anteroposterior/lateral radiographs, lateral flexion/extension radiographs, and computed tomography images taken at least 12 months after surgery. RESULTS: Forty-four patients treated at 49 levels completed follow-up. The mean patient age was 54.7 ± 10.8 years, and mean body mass index was 30.8 ± 7.7 kg/m(2). Radiographic fusion was observed in 41 of 44 assessed levels (93.2%). Blood loss was less than 100 mL in 95.5% of patients. Of the patients, 93.2% spent 1 night or less in the hospital. By the 6-week follow-up, all clinical outcomes were significantly improved (P < .05). Improvements were maintained or increased throughout the course of follow-up. CONCLUSIONS: This report shows that the technique of extreme lateral approach to interbody fusion in combination with FormaGraft and BMA in the interbody space is a safe and effective treatment option for interbody fusion of the lumbar spine when compared with other approaches and biologic options.

Lumbar fusion in octogenarians: the promise of minimally invasive surgery.

STUDY DESIGN: Retrospective chart review of prospectively collected data from 2 nonrandomized, nonconcurrent cohorts. OBJECTIVE: Early results of 2 lumbar interbody fusion procedures-open posterior lumbar interbody fusion (PLIF) and minimally invasive (extreme lateral interbody fusion [XLIF])-were compared in octogenarians to demonstrate the safety of each in the extreme elderly populations. SUMMARY OF BACKGROUND DATA: Although spinal pathologies are common in the elderly patients, additional health conditions often preclude operative treatment because anesthesia, blood loss, and recovery are too demanding. Minimally invasive approaches reduce procedure-related morbidity and recovery time. METHODS: In our single-site prospective series of XLIF patients, 40 were identified as those aged ≥80 years with a minimum of 3-month follow-up. A complete, retrospective review of surgical patients treated in the same practice with traditional open posterior (PLIF) approach found 20 patients aged ≥80 years. Comparisons were made between groups to identify differences in morbidity and mortality rates. RESULTS: No clinically significant differences in demographics, diagnoses, or comorbidities were found between groups. Complication rate, blood loss/transfusion rate, and hospital stay were significantly lower in the minimally invasive surgery (MIS) group (P < 0.0001). MIS patients left the hospital an average of 4 days earlier than the open PLIF patients, most discharged home (92.5% XLIF vs. 0% PLIF) rather than to skilled nursing facilities. Six deaths occurred in the PLIF follow-up, 3 within 3 months postoperatively; there was 1 death at 6 months postoperatively XLIF. CONCLUSION: Surgical treatment need not be withheld on the basis of age; elderly patients can successfully be treated using MIS techniques, and are-in our experience-among the most satisfied with their outcomes, enjoying significant improvements in pain, mobility, and quality of life.

Role of the cocatalyst in the copolymerization of CO2 and cyclohexene oxide utilizing chromium salen complexes.

The mechanism of the copolymerization of cyclohexene oxide and carbon dioxide to afford poly(cyclohexylene)carbonate catalyzed by (salen)CrN3 (H2salen = N,N,'-bis(3,5-di-tert-butylsalicylidene)-1,2-ethylene-diimine) in the presence of a broad range of cocatalysts has been studied. We have previously established the rate of copolymer formation to be very sensitive to both the electron-donating ability of the salen ligand and the [cocatalyst], where N-heterocyclic amines, phosphines, and ionic salts were effective cocatalysts. Significant increases in the rate of copolymerization have been achieved with turnover frequencies of approximately 1200 h(-1), thereby making these catalyst systems some of the most active and robust thus far uncovered. Herein we offer a detailed explanation of the role of the cocatalyst in the copolymerization of CO2 and cyclohexene oxide catalyzed by chromium salen derivatives. A salient feature of the N-heterocyclic amine- or phosphine-cocatalyzed processes is the presence of an initiation period prior to reaching the maximum rate of copolymerization. Importantly, this is not observed for comparable processes involving ionic salts as cocatalysts, e.g., PPN+ X-. In these latter cases the copolymerization reaction exhibits ideal kinetic behavior and is proposed to proceed via a reaction pathway involving anionic six-coordinate (salen)Cr(N3)X- derivatives. By way of infrared and 31P NMR spectroscopic studies, coupled with in situ kinetic monitoring of the reactions, a mechanism of copolymerization is proposed where the neutral cocatalysts react with CO2 and/or epoxide to produce inner salts or zwitterions which behave in a manner similar to that of ionic salts.

Cyclohexene oxide/CO2 copolymerization catalyzed by chromium(III) salen complexes and N-methylimidazole: effects of varying salen ligand substituents and relative cocatalyst loading.

A detailed mechanistic study into the copolymerization of CO2 and cyclohexene oxide utilizing CrIII(salen)X complexes and N-methylimidazole, where H2salen = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-ethylenediimine and other salen derivatives and X = Cl or N3, has been conducted. By studying salen ligands with various groups on the diimine backbone, we have observed that bulky groups oriented perpendicular to the salen plane reduce the activity of the catalyst significantly, while such groups oriented parallel to the salen plane do not retard copolymer formation. This is not surprising in that the mechanism for asymmetric ring opening of epoxides was found to occur in a bimetallic fashion, whereas these perpendicularly oriented groups along with the tert-butyl groups on the phenolate rings produce considerable steric requirements for the two metal centers to communicate and thus initiate the copolymerization process. It was also observed that altering the substituents on the phenolate rings of the salen ligand had a 2-fold effect, controlling both catalyst solubility as well as electron density around the metal center, producing significant effects on the rate of copolymer formation. This and other data discussed herein have led us to propose a more detailed mechanistic delineation, wherein the rate of copolymerization is dictated by two separate equilibria. The first equilibrium involves the initial second-order epoxide ring opening and is inhibited by excess amounts of cocatalyst. The second equilibrium involves the propagation step and is enhanced by excess cocatalyst. This gives the [cocatalyst] both a positive and negative effect on the overall rate of copolymerization.

(Salen)CrIIIX catalysts for the copolymerization of carbon dioxide and epoxides: role of the initiator and cocatalyst.

The copolymerization of CO(2) and cyclohexene or propylene oxide has been examined employing (salen)Cr(III)Nu complexes (Nu = Cl or N(3)) as catalysts. The addition of various cocatalysts, including phosphines and PPN+ or Bu4N+ Cl- salts serves to greatly enhance the rate of copolymer production. In these instances, the mechanism of the initiation step appears to be unimolecular in catalyst concentration, unlike the bimolecular process cocatalyzed by N-methylimidazole. The copolymers were produced with >95% carbonate linkages with TOFs in the range 39-494 mol epoxide consumed/mol Cr.h. In the presence of phosphine cocatalysts, no cyclic carbonate was produced as a byproduct.

The copolymerization of carbon dioxide and [2-(3,4-epoxycyclohexyl)ethyl]trimethoxysilane catalyzed by (salen)CrCl. Formation of a CO2 soluble polycarbonate.

The copolymerization of 2-(3,4-epoxycyclohexyl)ethyl-trimethoxysilane and carbon dioxide catalyzed by (salen)Cr(III)Cl (H(2)salen = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-ethylenediimine) with 2.5 equiv of N-MeIm as cocatalyst affords a polycarbonate devoid of polyether linkages, along with only a trace quantity of cyclic carbonate. The presence of the trimethoxysilane functionality in the epoxide not only provided the reactant monomer and product copolymer high solubility in liquid carbon dioxide but also provided the ability to cross-link the copolymer and thereby greatly alter the physical properties of the thus formed polycarbonate. In addition, the enhanced solubility of the copolymer in liquid CO(2) furnishes a ready means of removing the highly colored metal catalyst from the polycarbonate product.

Carbon dioxide/epoxide coupling reactions utilizing Lewis base adducts of zinc halides as catalysts. Cyclic carbonate versus polycarbonate production.

The reactions of zinc halides with 2,6-di-methoxypyridine or 3-trifluoromethylpyridine in dichloromethane have led to the formation of quite different complexes. Specifically, reactions involving pyridine containing electron donating methoxy substitutents have provided salts of the type [Zn(2,6-dimethoxypyridine)4][Zn2X6], as revealed by elemental analysis and X-ray crystallography. On the other hand, simple bis-pyridine adducts of zinc halides were isolated from the reactions involving the pyridine ligand with electron withdrawing substituents and characterized by X-ray crystallography, for example, Zn(3-trifluoromethylpyridine)2Br2. These zinc complexes were shown to be catalytically active for the coupling of carbon dioxide and epoxides to provide high molecular weight polycarbonates and cyclic carbonates, with the order of reactivity being Cl > or = Br > I, and 2,6-di-methoxypyridine > 3-trifluoromethylpyridine. Polycarbonate production from carbon dioxide and cyclohexene oxide was shown to be first-order in both metal precursor complex and cyclohexene oxide, as monitored by in situ infrared spectroscopy at 80 degrees C and 55 bar pressure. For reactions carried out in CO2 swollen epoxide solutions in the absence of added quantities of pyridine, the copolymer produced contained significant polyether linkages. Alternatively, reactions performed in the presence of excess pyridine or in hydrocarbon solvent, although slower in rate, afforded completely alternating copolymers. For comparative purposes, zinc chloride was a very effective homopolymerization catalyst for polyethers. Additionally, zinc chloride afforded copolymers with 60% carbonate linkages in the presence of high carbon dioxide pressures. In the case of cyclohexene oxide, the copolymer back-biting reaction led exclusively to the production of the trans cyclic carbonate as shown by infrared spectroscopy in v(C=O) region and X-ray crystallography. The unique feature of these catalyst systems is their simplicity.