B(C₆F₅)₃ Activation of Oxo Tungsten Complexes That Are Relevant to Olefin Metathesis

We have found that coordination of B­(C₆F₅)₃ to an oxo ligand in tungsten oxo alkylidene bis­(aryloxide) complexes, where the aryloxide is O-2,6-(mesityl)₂C₆H₃ (HMTO) or 2,6-diadamantyl-4-methylphenoxide (dAdPO), accelerates the formation of metallacyclobutane complexes from alkylidenes as well as the rearrangement of metallacyclobutane complexes. In contrast, a tungstacyclopentane complex, W­(O)­(C₄H₈)­(OHMT)₂, is relatively stable toward rearrangement in the presence of B­(C₆F₅)₃. A careful balance of steric factors allows a single isomer of W­(O)­(<i>trans</i>-4,4-dimethylpent-2-ene)­(dAdPO)₂ to be formed from W­(O)­(CH-<i>t</i>-Bu)­(dAdPO)₂ in the presence of both ethylene and B­(C₆F₅)₃

Allylic Aminations with Hindered Secondary Amine Nucleophiles Catalyzed by Heterobimetallic Pd–Ti Complexes

Phosphinoamide-scaffolded heterobimetallic palladium–titanium complexes are highly effective catalysts for allylic aminations of allylic chlorides with hindered secondary amine nucleophiles. Three titanium-containing ligands are shown to assemble active catalysts <i>in situ</i> and enable catalysis at room temperature. A variety of sterically bulky secondary amines are efficiently allylated in high yields with as little as 1 mol % palladium catalyst. Piperidine and pyrrolidine products are also efficiently generated via intramolecular aminations with hindered amine nucleophiles

B(C₆F₅)₃ Activation of Oxo Tungsten Complexes That Are Relevant to Olefin Metathesis

We have found that coordination of B­(C₆F₅)₃ to an oxo ligand in tungsten oxo alkylidene bis­(aryloxide) complexes, where the aryloxide is O-2,6-(mesityl)₂C₆H₃ (HMTO) or 2,6-diadamantyl-4-methylphenoxide (dAdPO), accelerates the formation of metallacyclobutane complexes from alkylidenes as well as the rearrangement of metallacyclobutane complexes. In contrast, a tungstacyclopentane complex, W­(O)­(C₄H₈)­(OHMT)₂, is relatively stable toward rearrangement in the presence of B­(C₆F₅)₃. A careful balance of steric factors allows a single isomer of W­(O)­(<i>trans</i>-4,4-dimethylpent-2-ene)­(dAdPO)₂ to be formed from W­(O)­(CH-<i>t</i>-Bu)­(dAdPO)₂ in the presence of both ethylene and B­(C₆F₅)₃

High Oxidation State Molybdenum Imido Heteroatom-Substituted Alkylidene Complexes

Reactions between Mo­(NAr)­(CHR)­(Me₂Pyr)­(OTPP) (Ar = 2,6-<i>i</i>-Pr₂C₆H₃, R = H or CHCMe₂Ph, Me₂Pyr = 2,5-dimethylpyrrolide, OTPP = O-2,3,5,6-Ph₄C₆H) and CH₂CHX where X = B­(pin), SiMe₃, <i>N</i>-carbazolyl, <i>N</i>-pyrrolidinonyl, PPh₂, OPr, or SPh lead to Mo­(NAr)­(CHX)­(Me₂Pyr)­(OTPP) complexes in good yield. All have been characterized through X-ray studies (as an acetonitrile adduct in the case of X = PPh₂). The efficiencies of metathesis reactions initiated by Mo­(NAr)­(CHX)­(Me₂Pyr)­(OTPP) complexes can be rationalized on the basis of steric factors; electronic differences imposed as a consequence of X being bound to the alkylidene carbon do not seem to play a major role. Side reactions that promote catalyst decomposition do not appear to be a serious limitation for MoCHX species

High Oxidation State Molybdenum Imido Heteroatom-Substituted Alkylidene Complexes

Reactions between Mo­(NAr)­(CHR)­(Me₂Pyr)­(OTPP) (Ar = 2,6-<i>i</i>-Pr₂C₆H₃, R = H or CHCMe₂Ph, Me₂Pyr = 2,5-dimethylpyrrolide, OTPP = O-2,3,5,6-Ph₄C₆H) and CH₂CHX where X = B­(pin), SiMe₃, <i>N</i>-carbazolyl, <i>N</i>-pyrrolidinonyl, PPh₂, OPr, or SPh lead to Mo­(NAr)­(CHX)­(Me₂Pyr)­(OTPP) complexes in good yield. All have been characterized through X-ray studies (as an acetonitrile adduct in the case of X = PPh₂). The efficiencies of metathesis reactions initiated by Mo­(NAr)­(CHX)­(Me₂Pyr)­(OTPP) complexes can be rationalized on the basis of steric factors; electronic differences imposed as a consequence of X being bound to the alkylidene carbon do not seem to play a major role. Side reactions that promote catalyst decomposition do not appear to be a serious limitation for MoCHX species

Nickel-Catalyzed Suzuki Cross Couplings with Unprotected Allylic Alcohols Enabled by Bidentate <i>N</i>‑Heterocyclic Carbene (NHC)/Phosphine Ligands

Cross couplings between simple allylic alcohols and aryl and vinyl boronic acids are efficiently catalyzed by nickel(0) catalysts and bidentate <i>N</i>-heterocyclic carbene/phosphine ligands. The bidentate nature of the ligand is shown to extend catalyst lifetime and enable high yields of the corresponding cross-coupling products. X-ray crystallography confirms the bidentate nature of the ligand scaffold. Multistep cross coupling-alkene/alkyne insertions reactions are also conducted and the bidentate nature of the substrate makes the pendant phosphine of the ligand unnecessary

Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels–Alder Reaction and Di‑<i>t</i>‑butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer <i>dl</i>-Deoxypodophyllotoxin

Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels–Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels–Alder pathway followed by a faster di-<i>t</i>-butylhydroxytoluene assisted [1,3]-formal hydrogen shift

Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels–Alder Reaction and Di‑<i>t</i>‑butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer <i>dl</i>-Deoxypodophyllotoxin

Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels–Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels–Alder pathway followed by a faster di-<i>t</i>-butylhydroxytoluene assisted [1,3]-formal hydrogen shift

Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels–Alder Reaction and Di‑<i>t</i>‑butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer <i>dl</i>-Deoxypodophyllotoxin

Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels–Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels–Alder pathway followed by a faster di-<i>t</i>-butylhydroxytoluene assisted [1,3]-formal hydrogen shift

Intramolecular Heteroatom and Styryl Diels–Alder Reactions, Asymmetric Cycloadditions of Chiral 3‑Phenylallyl Maleic Esters

Polycyclic aryl naphthalene and tetralin dihydro arylnaphthalene lactone lignans possess anticancer and antibiotic activity. Related furo[3,4-c]pyranones, typified by the sequester-terpenoid isobolivianine, show similar antiproliferative bioactivity. Efficient syntheses of compounds featuring these polycyclic cores have proven challenging due to low yields and poor stereoselectivity. We report the synthesis of chiral cinnamyl but-2-enanoates and 3,3-diphenylallyl-but-2-enoates 1 as new Diels–Alder substrates. These compounds undergo [4 + 2]-cycloadditions to give furo[3,4-c]pyranones 2 in good yield (70%) and diastereoselectivity (7:1), together with naphthyl 3 and dihydronaphthyl tetralins 4 as minor products. Molecular structures and stereochemistries of the major products were verified using X-ray diffraction. Density functional theory calculations revealed that the cycloaddition process involves a bispericyclic/ambimodal process where there is a single transition state that leads to both intramolecular styryl Diels–Alder (ISDA) 3, 4 and intramolecular hetero Diels–Alder (IHDA) cycloadducts 2. With the elevated temperature conditions after cycloaddition, the resulting ISDA cycloadduct either undergoes [3,3]-sigmatropic rearrangement to the more stable major IHDA product or aromatization leading to the phenyltetralin