Six-Step Synthesis of (±)-Lysergic Acid.

This article describes a concise synthesis of lysergic acid from simple aromatic precursors. The successful strategy relies on the coupling, dearomatization, and cyclization of a halopyridine with a 4-haloindole derivative in 6 total synthetic steps from commercial starting materials. In addition to highlighting the advantages of employing dearomative retrosynthetic analysis, the design is practical and anticipated to enable the synthesis of novel neuroactive compounds as exemplified by the synthesis of a novel natural product derivative, 12-chlorolysergic acid.

Partial Deoxygenative CO Homocoupling by a Diiron Complex.

One route to address climate change is converting carbon dioxide to synthetic carbon-neutral fuels. Whereas carbon dioxide to CO conversion has precedent in homo- and heterogeneous catalysis, deoxygenative coupling of CO to products with C-C bonds-as in liquid fuels-remains challenging. Here, we report coupling of two CO molecules by a diiron complex. Reduction of Fe2 (CO)2 L (2), where L2- is a bis(ß-diketiminate) cyclophane, gives [K(THF)5 ][Fe2 (CO)2 L] (3), which undergoes silylation to Fe2 (CO)(COSiMe3 )L (4). Subsequent C-OSiMe3 bond cleavage and C=C bond formation occurs upon reduction of 4, yielding Fe2 (µ-CCO)L. CO derived ligands in this series mediate weak exchange interactions with the ketenylidene affording the smallest J value, with changes to local metal ion spin states and coupling schemes (ferro- vs. antiferromagnetism) based on DFT calculations, Mössbauer and EPR spectroscopy. Finally, reaction of 5 with KEt3 BH or methanol releases the C2 O2- ligand with retention of the diiron core.

Dinitrogen Coordination to a High-Spin Diiron(I/II) Species.

Dinitrogen coordination to iron centers underpins industrial and biological fixation in the Haber-Bosch process and by the FeM cofactors in the nitrogenase enzymes. The latter employ local high-spin metal centers; however, iron-dinitrogen coordination chemistry remains dominated by low-valent states, contrasting the enzyme systems. Here, we report a high-spin mixed-valent cis-(µ-1,2-dinitrogen)diiron(I/II) complex [(FeBr)2 (µ-N2 )Lbis ]- (2), where [Lbis ]- is a bis(ß-diketiminate) cyclophane. Field-applied Mössbauer spectra, dc and ac magnetic susceptibility measurements, and computational methods support a delocalized S=7 /2 Fe2 N2 unit with D=-5.23 cm-1 and consequent slow magnetic relaxation.

Synthetic Factors Governing Access to Tris(ß-diketimine) Cyclophanes versus Tripodal Tri-ß-aminoenones.

Tris(ß-diketimine) cyclophanes are an important ligand class for investigating cooperative multimetallic interactions of bioinorganic clusters. Discussed herein are the synthetic factors governing access to tris(ß-diketimine) cyclophanes versus tripodal tri-ß-aminoenones. Cyclophanes bearing Me, Et, and MeO cap substituents and ß-Me, Et, or Ph arm substituents are obtained, and a modified condensation method produced α-Me ß-Me cyclophane. These operationally simple procedures produce the ligands in gram quantities and in 22-94% yields.

Evaluating Metal Ion Identity on Catalytic Silylation of Dinitrogen Using a Series of Trimetallic Complexes.

We report catalytic silylation of dinitrogen to tris(trimethylsilyl)amine by a series of trinuclear first row transition metal complexes (M = Cr, Mn, Fe, Co, Ni) housed in our tris(ß-diketiminate) cyclophane (L 3- ). Yields are expectedly dependent on metal ion type ranging from 14 to 199 equiv NH4 +/complex after protonolysis for the Mn to Co congeners, respectively. For the series of complexes, the number of turnovers trend observed is Co > Fe > Cr > Ni > Mn, consistent with prior reports of greater efficacy of Co over Fe in other ligand systems for this reaction.

Palladium(II)-Catalyzed ortho-Arylation of Aromatic Alcohols with a Readily Attachable and Cleavable Molecular Scaffold.

A palladium(II)-catalyzed C-H arylation process of alcohols has been developed. The strategy utilizes a novel quinoline-based hemiacetal scaffold that can direct the selective C-H bond functionalization. This reaction provides a useful method to construct biaryl compounds of benzyl alcohols in good to excellent yields. The new molecular scaffold can be readily attached, removed, and recovered.

An analysis of the complementary stereoselective alkylations of imidazolidinone derivatives toward α-quaternary proline-based amino amides.

Alkylations of proline-based imidazolidinones are described based on the principle of self-regeneration of stereocenters (SRS), affording high levels of either the cis or trans configured products. Stereoselectivity is dictated solely on the nature of the "temporary" group, where isobutyraldehyde-derived imidazolidinones provide the cis configured products and 1-naphthaldehyde-derived imidazolidinones afford the complementary trans configured products. These stereodivergent products can be readily cleaved to afford both α-alkylated proline enantiomers from readily available L-proline. A series of imidazolidinones were alkylated to investigate the origin of the anti-selectivity. Potential contributions toward the observed anti-selectivity are discussed on the basis of these experiments, suggesting a refined hypothesis for selectivity may be in order.

A predictive model for additions to N-alkyl pyridiniums.

Disclosed in this communication is a thorough study on the dearomative addition of organomagnesium nucleophiles to N-alkyl pyridinium electrophiles. The regiochemical outcomes have observable and predictable trends associated with the substituent patterns on the pyridinium electrophile. Often, the substituent effects can be either additive, giving high selectivities, or ablative, giving competing outcomes. Additionally, the nature of the organometallic nucleophilic component was also investigated for its role in the regioselective outcome. The effects of either reactive component are important to both the overall reactivity and site of nucleophilic addition. The utility of these observed trends is demonstrated in a concise, dearomative synthesis of a tricyclic compound shown to have insecticidal activity.

Isolation of chloride- and hydride-bridged tri-iron and -zinc clusters in a tris(ß-oxo-δ-diimine) cyclophane ligand.

A cyclophane ligand (H6L) bearing three ß-oxo-δ-diimine arms and the corresponding tri-iron and -zinc complexes in which the metal ions are bridged by either chlorides, viz. Fe3Cl3(H3L) (1) and Zn3Cl3(H3L) (2), or hydrides, viz. Fe3H3(H3L) (3), Zn3H3(H3L) (4), were synthesized and characterized. 1 adopts a chair-shaped C3v-symmetric [Fe3(µ-Cl)3]3+ cluster wherein only one hemisphere of the ligand is metallated and the other three ketoimine sites remain protonated as evidenced by single crystal X-ray diffraction and vibrational and NMR spectroscopic analyses. 3 and 4 were synthesized by substitution of the bridging chlorides in 1 and 2 using KBEt3H and are accessed with retention of the three protonated ketoimine sites.

Catalytic Silylation of Dinitrogen by a Family of Triiron Complexes.

A series of triiron complexes supported by a tris(ß-diketiminate)cyclophane (L 3- ) catalyze the reduction of dinitrogen to tris(trimethylsilyl)amine using KC8 and Me3SiCl. Employing Fe3Br3 L affords 83 ± 7 equiv. NH4 +/complex after protonolysis, which is a 50% yield based on reducing equivalents. The series of triiron compounds tested evidences the subtle effects of ancillary donors, including halides, hydrides, sulfides, and carbonyl ligands, and metal oxidation state on N(SiMe3)3 yield, and highlight Fe3(µ3-N)L as a common species in product mixtures. These results suggest that ancillary ligands can be abstracted with Lewis acids under reducing conditions.

Reactivity of hydride bridges in a high-spin [Fe3(µ-H)3]3+ cluster: reversible H2/CO exchange and Fe-H/B-F bond metathesis.

The triiron trihydride complex Fe3H3L (1) [where L3- is a tris(ß-diketiminate)cyclophanate] reacts with CO and with BF3·OEt2 to afford (FeICO)2FeII(µ3-H)L (2) and Fe3F3L (3), respectively. Variable-temperature and applied-field Mössbauer spectroscopy support the assignment of two high-spin (HS) iron(i) centers and one HS iron(ii) ion in 2. Preliminary studies support a CO-induced reductive elimination of H2 from 1, rather than CO trapping a species from an equilibrium mixture. This complex reacts with H2 to regenerate 1 under a dihydrogen atmosphere, which represents a rare example of reversible CO/H2 exchange and the first to occur at high-spin metal centers, as well as the first example of a reversible multielectron redox reaction at a designed high-spin metal cluster. The formation of 3 proceeds through a previously unreported net fluoride-for-hydride substitution, and 3 is surprisingly chemically inert to Si-H bonds and points to an unexpectedly large difference between the Fe-F and Fe-H bonds in this high-spin system.

The design of a readily attachable and cleavable molecular scaffold for ortho-selective C-H alkenylation of arene alcohols.

We describe herein the design of a novel molecular scaffold that can induce facile oxidative olefinations when attached to alcohols. Benzylic, homo-, and bishomobenzylic alcohols are utilized. The scaffold can act as a protecting group for the alcohol in other transformations, and it is recoverable in excellent yield. The overall sequence can also be telescoped without purifications of intermediates, representing a net alcohol-based directed ortho-alkenylation.

Complementary stereochemical outcomes in proline-based self-regenerations of stereocenters.

Stereoselective alkylations of proline-based amino amides are described, where high levels of either a cis or trans configuration can be attained simply by the choice of the aminal group. Isobutryaldehyde-derived aminals provide the cis configuration, while 1-naphthaldehyde-derived aminals engender the complementary trans configuration.