An experimental and theoretical investigation of the carbon dioxide insertion process into the tungsten-nitrogen bond of an anionic W(0) complex.

The pyridine bound 2-aminopyridine (2APH) derivative of tungsten pentacarbonyl has been prepared from photogenerated W(CO)5THF and 2APH. Deprotonation of the distal amine group by sodium hydride has provided two complexes, [Na][W(CO)5(2AP)] and [Na]2[W(CO)4(2AP)]2. Both complexes have been characterized by X-ray crystallography with the monomeric derivative being crystallized as its [Na2(18-crown-6)][W(CO)5(2AP)]2 salt which exhibits strong Na+...-NH interactions. Photolysis of W(CO)6 in the presence of excess 2-aminopyridine in THF has led to an efficient synthesis of the chelated neutral derivative, W(CO)4(2APH).2APH, where the extra equivalent of 2APH is hydrogen bonded to its bound counterpart. The 2-aminopyridine molecule of solvation was almost quantitatively removed via aqueous washings. Deprotonation of W(CO)4(2APH) with NaH afforded the amidopyridine derivative which was shown to rapidly undergo reaction with CO2 to yield the chelated carbamate complex, W(CO)4(OC(O)2AP)-. Nevertheless, because of the presence of small quantities of free 2-aminopyridine during the reactions with CO2, we have not been able to conclusively rule out participation by a ligand substitution process involving NC5H4NHCOOH. Ab initio computations were found to substantiate many of these experimental observations. That is, in the monodentate bound W(CO)5(2APH) derivative, binding through the pyridine nitrogen atom is favored by about 29 kJ/mol over the amine nitrogen atom, whereas the opposite site for binding is preferred for the deprotonated amido analogue, W(CO)5(2AP)-. Furthermore, both forms of W(CO)5(2AP)- were found to be more stable than the chelated tungsten tetracarbonyl anion plus CO. On the other hand, CO2 insertion into the W(CO)4(2AP)- anion to provide the chelated carbamate, W(CO)4(OC(O)2AP)-, was thermodynamically favored by >110 kJ/mol. Finally, both experimental and theoretical studies were inconclusive with regard to identifying reaction intermediates during the CO2 insertion pathway which involve prior interactions of CO2 at the amido nitrogen center.

Solution and solid-state structures of phosphine adducts of monomeric zinc bisphenoxide complexes. Importance of these derivatives in CO2/epoxide copolymerization processes.

Phosphine derivatives of the monomeric zinc phenoxide complexes, (phenoxide)2ZnLn, where phenoxide equals 2,6-di-tert-butylphenoxide, 2,4,6-tri-tert-butylphenoxide, and 2,6-diphenylphenoxide and n = 1 or 2, have been synthesized from the reaction of Zn[N(SiMe3)2]2 and the corresponding phenol followed by the addition of phosphine. The complexes have been characterized in solution by 31P NMR spectroscopy and in selected instances in the solid-state by X-ray crystallography. The small, basic phosphine, PMe3, provided the only case of an isolated complex possessing two phosphine ligands (i.e., n = 2). For all other larger phosphines only the monophosphine adducts were obtained. Furthermore, only fairly basic phosphines were found to bind to zinc, e.g., whereas PPh3 (pKa = 2.73) was ineffective, PPh2Me (pKa = 4.57) did form a strong bond to zinc. The solid-state structures of the monophosphine adducts consist of a near-trigonal planar geometry about the zinc center, where the average P-Zn-O angles are larger than the O-Zn-O angles. On the other hand, the bisphosphine adduct, Zn(O-2,4,6-tBu3C6H2)(2).2PMe3, is a distorted tetrahedral structure with O-Zn-O and P-Zn-P bond angles of 108.8(2) degrees and 107.1(9) degrees, respectively. Competitive phosphine binding studies monitored by 31P NMR spectroscopy provided a relative binding order of PPh3 approximately PtBu3 << PPh2Me < PCy3 < PMe2Ph < PnBu3 < PEt3 < PMe3. Hence, the relative binding of basic phosphine ligands at these congested zinc sites is largely determined by their steric requirements. All phosphine adducts, with the exception of PMe2Ph and PMe3, were found to undergo slow self-exchange (< 600 s-1) with free phosphine by 31P NMR spectroscopy. However, the two small phosphines, PMe2Ph (cone angle = 122 degrees) and PMe3 (cone angle = 118 degrees), were shown to undergo rapid exchange presumably via an associative mechanism. Although there was no kinetic preferences for PCy3 binding to cadmium vs zinc, cadmium was thermodynamically favored by about a factor of 2.5. The addition of up to 3 equiv of PCy3 to the Zn(O-2,6-tBu2C6H3)2 or Zn(O-2,4,6-tBu3C6H2)2 derivatives did not significantly alter the reactivity of these catalysts for the copolymerization of cyclohexene oxide (CHO) and CO2 to high-molecular weight poly(cyclohexene carbonate). However, the presence of PCy3 greatly retarded their ability to homopolymerize CHO to polyether or to afford polyether linkages during the copolymerization of CHO/CO2.

Benefits of continuous physiological pulsatile gonadotropin-releasing hormone therapy in women with polycystic ovarian syndrome.

OBJECTIVE: Can continuous pulsatile GnRH from one ovulatory cycle to another enhance the endocrine milieu of women with polycystic ovarian syndrome (PCOS)? DESIGN: Five women with well-characterized, clomiphene citrate (CC)- and hMG-resistant PCOS were treated with a 100 ng/kg per bolus of IV pulsatile GnRH (Lutrepulse; Ortho Pharmaceutical Corporation, Raritan, NJ) every 90 minutes for two consecutive ovulatory cycles. Weekly vaginal ultrasonography and daily blood sampling for LH (mIU/mL), FSH (mIU/mL), E2 (pg/mL), and P (ng/mL) were performed. These data were compared with a control group of normally cycling women. RESULTS: First ovulatory cycles on therapy were characterized by significantly increased mean follicular phase LH = 88 (arbitrary units area under the curve [AUC]) compared with second cycles (28 mean AUC units) and controls (13 mean AUC units). Luteal phase E2 (3,081 mean AUC units) was significantly increased in first cycles compared with second cycles (880 mean AUC units) and controls (1,562 mean AUC units in PCOS). Luteal phase E2 secretion was elevated in second cycles when compared with normal but not significantly. The changes occurring between the first and second ovulatory cycles in women with PCOS resulted in a more physiological overall pattern of gonadotropin and sex steroid secretion in the second cycles. Two singleton pregnancies were achieved in the second cycle. CONCLUSIONS: Low-dose pulsatile IV GnRH can successfully induce ovulation in women with PCOS who have failed to conceive on all previous conventional therapy (CC, hMG, and/or GnRH agonist, and hMG). Continuous cycle-to-cycle physiological GnRH replacement normalized the endocrine parameters of second cycles. Women with PCOS, even when ovulatory on pulsatile GnRH, do not display entirely normal gonadotropin and sex steroid dynamics.