Craig A. Ogle

Preparation of σ- and π-Allylcopper(III) Intermediates in SN2 and SN2′ Reactions of Organocuprate(I) Reagents with Allylic Substrates

The first pi-allyl complexes of CuIII have been prepared and characterized by using rapid injection nuclear magnetic resonance spectroscopy (RI-NMR). The prototype, (eta3-allyl)dimethylcopper(III), was prepared by injection of allyl chloride into a THF-d8 solution of iodo-Gilman reagent, Me2CuLi.LiI (A), spinning in the probe of an NMR spectrometer at -100 degreesC. A sigma-allyl ate complex, lithium (eta1-allyl)trimethylcuprate(III), was prepared in high yield by including 1 equiv of tributylphosphine in the reaction mixture or by using allyl acetate as the substrate. Cyano ate complex, lithium cis-(eta1-allyl)cyanodimethylcuprate(III) was obtained in high yield by injecting allyl chloride or allyl acetate into the cyano-Gilman reagent, Me2CuLi.LiCN (B), in THF-d8 at -100 degrees C. Reactions of A with allylic substrates show a definite dependence on leaving group (chloride vs acetate), whereas those of B do not. Moreover, these reagents have different regioselectivities, which in the case of A vary with temperature. Finally, the exclusive formation of cis-cyano sigma-allyl CuIII intermediates in both the 1,4-addition of B to alpha-enones and its SN2alpha reaction with allylic substrates now makes sense in terms of pi-allyl intermediates in both cases, thus unifying the mechanisms of these two kinds of conjugate addition.

Opening the ‘black box’: oscillations in organocuprate conjugate addition reactions

Under the conditions of a rapid injection experiment, the conjugate addition reactions of butyl Gilman reagents with 2-cyclohexenone undergo oscillations of a complex nature.

The X-ray Crystal Structure of a Cuprate–Carbonyl π-Complex†

Complexes between copper reagents and double-bonds have been proposed as intermediates in a number of synthetically important reactions. Many h-complexes between organocuprates and carbon–carbon double-bonds, which are intermediates in 1,4-addition reactions of a,b-unsaturated carbonyl compounds, have been observed by using NMR spectroscopy. Moreover, h-O,C-complexes between organocopper compounds and carbon–oxygen double-bonds have been proposed as intermediates in 1,2-additions to carbonyl compounds, for example, copper-catalyzed asymmetric induction reactions. Carbophilic additions to thiocarbonyl compounds, mediated by organocuprates, have been explained in terms of h-S,C-complexes of carbon–sulfur double-bonds. However, there has been no report of an X-ray structure for any of these p-complexes. Therefore, we applied our rapid-injection techniques, which were previously used to prepare several important intermediates, to screen a number of typical aldehydes and ketones for complex formation with Me2CuLi, [9] and we discovered such a species with unusual stability, which has allowed us to prepare it on a larger scale and grow highquality crystals (see the Supporting Information). We now report the first X-ray crystal structure of a cuprate– carbonyl p-complex, 1 (Scheme 1 and Figure 1).

Complexes of Gilman Reagents with C−S and C−N Double Bonds: σ or π Bonding?

Upon rapid injection, a variety of thiocarbonyl compounds react with the Gilman reagent Me(2)CuLi at -100 degrees C inside the probe of an NMR spectrometer to give high yields of complexes. Typical examples of substrates include carbon disulfide, methyl dithioacetate, methyl dithiobenzoate, thiobenzophenone, ethylene trithiocarbonate, and phenyl isothiocyanate. Evidence suggesting the formal oxidation state of copper in these complexes to be Cu(III) is presented. The last example was particularly interesting, since it involved a transient intermediate that was identified as a complex with a C-N double bond. Methyl isothiocyanate gave a stable C-N double-bond complex.

Urotropin azelate: a rather unwilling co-crystal

Urotropin (U) and azelaic acid (AA) form 1:1 co-crystals (UA) that give rise to a rather complex diffraction pattern, the main features of which are diffuse rods and bands in addition to the Bragg reflections. UA is characterized by solvent inclusions, parasite phases, and high vacancy and dislocation densities. These defects compounded with the pronounced tendency of U to escape from the crystal edifice lead to at least seven exotic phase transitions (many of which barely manifest themselves in a differential scanning calorimetry trace). These involve different incommensurate phases and a peritectoid reaction in the recrystallization regime (T(h) > 0.6). The system may be understood as an OD (order-disorder) structure based on a layer with layer group P(c)c2 and cell a(o) approximately 4.7, b approximately 26.1 and c approximately 14.4 A. At 338 K the layer stacking is random, but with decreasing temperature the build-up of an orthorhombic MDO (maximal degree of order) structure with cell a(1) = 2a(o), b(1) = b, c(1) = c and space group Pcc2 is begun (at approximately 301 K). The superposition structure of the OD system at T = 286 (1) K with space group Bmmb and cell â = 2a(o), b = b and ĉ = c/2 owes its cohesion to van der Waals interactions between the AA chains and to three types of hydrogen bonds of varied strength between U-U and U-AA. Before reaching completion, this MDO structure is transformed, at 282 K, into a monoclinic one with cell a(m) = -a(o) + c/4, b(m) = b, c(m) = -2(a(o) + c/2), space group P2(1)/c, spontaneous deformation approximately 2 degrees, and ferroelastic domains. This transformation is achieved in two steps: first a furtive triggering transition, which is not yet fully understood, and second an improper ferroelastic transition. At approximately 233 K, the system reaches its ground state (cell a(M) = a(m), b(M) = b, c(M) = c(m) and space group P2(1)/c) via an irreversible transition. The phase transitions below 338 K are described by a model based on the interaction of two thermally activated slip systems. The OD structure is described in terms of a three-dimensional Monte Carlo model that involves first- and second-neighbour interactions along the a axis and first-neighbour interactions along the b and c axes. This model includes random shifts of the chains along their axes and satisfactorily accounts for most features that are seen in the observed diffraction pattern.

A novel approach to tricyclic pharmaceuticals via directed dilithiation of diaryl compounds

Abstract Tricyclic compounds were prepared using a novel approach based on the reaction between dilithio-diphenyl ether with appropriately substituted esters. The pharmaceutical drug, clopipazan, and its corresponding deschloro analog were synthesized utilizing this approach.

Aldehydes and Ketones Form Intermediate π Complexes with the Gilman Reagent, Me2CuLi, at Low Temperatures in Tetrahydrofuran

Typical aldehydes and ketones form π complexes with Me2CuLi at low temperatures in tetrahydrofuran. They range in stability from fleeting intermediates at -100 °C to entities that persist up to -20 °C. Three subsequent reaction pathways have been identified.

A rapid‐injection NMR study of the effect of lithium alkoxides on the butyllithium‐initiated polymerization and propagation of styrene

In studies carried out in THF at 280°C, lithium n-butoxide was found to speed up the initiation and to an even greater extent the rate of propagation in the alkyllithium-initiated polymerization of styrene. Bulky alkoxides were found to slow down the rate of polymerization by slowing both initiation and propagation although initiation was decreased to a greater extent than propagation. Five equivalents of lithium tert-butoxide stopped the initiation completely under these reaction conditions when n-butyllithium was used as an initiator.

Chloro(1,5-cyclo­octa­diene)(tri­phenyl­phosphine)­rhodium(I)

The crystal and molecular structure of the title compound, [RhCl(C8H12){P(C6H5)3}], has been determined by means of X-ray diffraction. Compounds of this nature are important because of their ability to act as homogenous hydrogenation catalysts and to serve as precursors for more elaborate compounds.

First X‐Ray Crystal Structure and Internal Reference Diffusion‐Ordered NMR Spectroscopy Study of the Prototypical Posner Reagent, MeCu(SPh)Li(THF)3

Grow slow: The usual direct treatment of MeLi and CuSPh did not yield X-ray quality crystals of MeCu(SPh)Li. An indirect method starting from Me2CuLi⋅LiSPh and chalcone afforded the desired crystals by the slow reaction of the intermediate π-complex (see scheme). This strategy produced the first X-ray crystal structure of a Posner cuprate. A complementary NMR study showed that the contact ion pair was also the main species in solution.