Earth abundant, first row transition metals offer a cheap and sustainable alternative to the rare and precious metals. However, utilization of first row metals in catalysis requires harsh reaction conditions, suffers from limited activity, and fails to tolerate functional groups. Reported here is a highly efficient iron catalyzed hydroformylation of alkenes under mild conditions. This protocol operates at 10-30 bar syngas pressure below 100 °C, utilizes readily available ligands, and applies to an array of olefins. Thus, the iron precursor [HFe(CO)][PhPNPPh] (1) in the presence of triphenyl phosphine catalyzes the hydroformylation of 1-hexene (S2), 1-octene (S1), 1-decene (S3), 1-dodecene (S4), 1-octadecene (S5), trimethoxy(vinyl)silane (S6), trimethyl(vinyl)silane (S7), cardanol (S8), 2,3-dihydrofuran (S9), allyl malonic acid (S10), styrene (S11), 4-methylstyrene (S12), 4- iBu-styrene (S13), 4- tBu-styrene (S14), 4-methoxy styrene (S15), 4-acetoxy styrene (S16), 4-bromo styrene (S17), 4-chloro styrene (S18), 4-vinylbenzonitrile (S19), 4-vinylbenzoic acid (S20), and allyl benzene (S21) to corresponding aldehydes in good to excellent yields. Both electron donating and electron withdrawing substituents could be tolerated and excellent conversions were obtained for S11-S20. Remarkably, the addition of 1 mol % acetic acid promotes the reaction to completion within 16-24 h. Detailed mechanistic investigations revealed in situ formation of an iron-dihydride complex [HFe(CO)(PPh)] (A) as an active catalytic species. This finding was further supported by cyclic voltammetry investigations and intermediacy of an Fe(0)-Fe(II) species was established. Combined experimental and computational investigations support the existence of an iron-dihydride as the catalyst resting state, which then follows a Fe(II) based catalytic cycle to produce aldehyde.

A site-selective C-4/C-8 alkynylation of isoquinolones catalyzed by gold and rhodium complexes is reported. A broad range of synthetically useful functional groups (-F, -Cl, -Br, -CF3, -OMe, alkyl, etc.) were tolerated, providing an efficient and robust protocol for the synthesis either C-4- or C-8-alkynylated isoquinolones.

A unified strategy for cobalt-catalyzed ortho-C-H bond alkynylation of benzylamines is reported. Simple, commercially available CoBr was used as a cobalt source. The developed alkynylation strategy is robust and efficient and has a broad substrate scope including 1°, 2°, and 3° benzylamines. The mechanistic study shows that C-H bond cleavage is reversible, and the kinetic study illustrates that the rate of reaction depends solely on the catalyst.

A co-operative Au(i)/Ag(i) catalyst system has been developed to utilize N-allenamides as nucleophilic enal equivalents for the interceptive capturing of incipient carbocations generated through π-acid-triggered imino-alkyne cyclization. The salient features include the in situ generation of silver-bound carbocations (from iminoalkynes), α-gold(i) enals (from N-allenamides) and union of these two species to form indolizines with the regeneration of Au and Ag catalysts.

Supramolecular phosphine-derived catalysts are known to provide high enantioselectivity in asymmetric transformations such as hydrogenation, but direct evidence unravelling the role of secondary interactions is largely missing. As a representative case study, the role of hydrogen bonding in asymmetric hydrogenation catalysed by p-chiral supramolecular phosphines is investigated. To establish the nature of hydrogen bonding in the self-assembled Rh-complex, NMR experiments were performed at different concentrations and temperatures. It was found that with increasing concentration of 1-(3-(phenyl(o-tolyl)phosphanyl)phenyl)urea ligand (L1), the NH and NH peaks shift downfield. This indicated the presence of intermolecular hydrogen bonding in L1. This observation was further supported by variable temperature NMR experiments wherein, with decreasing temperature, the NH and NH resonances of L1 shifted downfield. The downfield shift once again suggests the existence of intermolecular hydrogen bonding in L1. In contrast, the chemical shift of NH and NH signals did not significantly change with increasing concentration of the self-assembled Rh-complex (C1). This observation suggested the existence of intramolecular hydrogen bonding in the self-assembled complex. The concentration experiment was further corroborated by variable temperature NMR experiments. No change in the chemical shift of NH resonance could be detected with decreasing temperature, which corroborates the existence of intramolecular hydrogen bonding in C1. In a stoichiometric experiment, C1 was treated with hydrogenation substrate N-acetyldehydrophenylalanine (S2) and the proton NMR was recorded. The NH protons of the self-assembled Rh-complex were found to shift downfield, as compared to untreated parent C1. These observations indicated that there is a hydrogen bonding interaction between the Rh-complex and the substrate. To further attest this hypothesis, NH and NH groups were exchanged with ND and ND groups, respectively, and a self-assembled Rh-complex was prepared using the deuterated supramolecular phosphine ligand L1.D. When the deuterated Rh-complex (C1.D) was treated with substrate S2, the ND and ND resonances were found to shift downfield. Thus, the labelling experiment further authenticated the existence of catalyst-substrate interactions. The presence of this catalyst-substrate interaction could be one of the parameters that leads to high enantiomeric excess in the asymmetric hydrogenation reaction of S2.

Discovered by Hugo Schiff, condensation between amine and aldehyde represents one of the most ubiquitous reactions in chemistry. This classical reaction is widely used to manufacture pharmaceuticals and fine chemicals. However, the rapid and reversible formation of Schiff base prohibits formation of alternative products, of which benzoxazinones are an important class. Therefore, manipulating the reactivity of two partners to invert the course of this reaction is an elusive target. Presented here is a synthetic strategy that regulates the sequence of Schiff base reaction via weak secondary interactions. Guided by the computational models, reaction between 2,3,4,5,6-pentafluoro-benzaldehyde with 2-amino-6-methylbenzoic acid revealed quantitative (99%) formation of 5-methyl-2-(perfluorophenyl)-1,2-dihydro-4H-benzo[d][1,3]oxazin-4-one (15). Electron donating and electron withdrawing ortho-substituents on 2-aminobenzoic acid resulted in the production of benzoxazinones 9-36. The mode of action was tracked using low temperature NMR, UV-vis spectroscopy, and isotopic (O) labeling experiments. These spectroscopic mechanistic investigations revealed that the hemiaminal intermediate is arrested by the hydrogen-bonding motif to yield benzoxazinone. Thus, the mechanistic investigations and DFT calculations categorically rule out the possibility of in situ imine formation followed by ring-closing, but support instead hydrogen-bond assisted ring-closing to prodrugs. This unprecedented reaction represents an interesting and competitive alternative to metal catalyzed and classical methods of preparing benzoxazinone.

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A small library of bisphosphorus ligands was evaluated in the rhodium‐catalyzed isomerizing hydroformylation (I‐HF) of cashew nut shell liquid (CNSL). The rhodium complex of 1,2‐bis((di‐tert‐butylphosphanyl)methyl)benzene (BDTBPMB; L4) outperformed the other bisphosphite and bisphosphine ligands and unveiled a moderate selectivity of 28 % and 50 % in the I‐HF of CNSL monoene and methoxy‐protected monoene, respectively. The resultant aldehyde 16‐(3‐methoxyphenyl)hexadecanal P1′ was isolated and its identity was fully established. Application of bis‐phosphine ligand L4 in the I‐HF of highly challenging CNSL cardanol (S3) and methoxy‐protected CNSL cardanol yielded a linear selectivity of 74 %, although with reduced conversion. To demonstrate the synthetic utility of our strategy, the obtained aldehyde (derived from S3) was subjected to hydrogenation and the resultant 3‐(16‐hydroxyhexadecyl) phenol (P8) was isolated in 89 % isolated yield. High‐pressure NMR investigation revealed selective formation of a bis‐equatorial BDTBPMB–rhodium complex, which might be responsible for the excellent linear selectivity.