Nickel-catalyzed ester carbonylation promoted by imidazole-derived carbenes and salts.

Millions of tons of acetyl derivatives such as acetic acid and acetic anhydride are produced each year. These building blocks of chemical industry are elaborated into esters, amides, and eventually polymer materials, pharmaceuticals, and other consumer products. Most acetyls are produced industrially using homogeneous precious metal catalysts, principally rhodium and iridium complexes. We report here that abundant nickel can be paired with imidazole-derived carbenes or the corresponding salts to catalyze methyl ester carbonylation with turnover frequency (TOF) exceeding 150 hour-1 and turnover number (TON) exceeding 1600, benchmarks that invite comparisons to state-of-the-art rhodium-based systems and considerably surpass known triphenylphosphine-based nickel catalysts, which operate with TOF ~7 hour-1 and TON ~100 under the same conditions.

The potentials and challenges of using fermentation to improve the sensory quality of plant-based meat analogs.

Despite the advancements made in improving the quality of plant-based meat substitutes, more work needs to be done to match the texture, appearance, and flavor of real meat. This review aims to cover the sensory quality constraints of plant-based meat analogs and provides fermentation as a sustainable approach to push these boundaries. Plant-based meat analogs have been observed to have weak and soft textural quality, poor mouth feel, an unstable color, and unpleasant and beany flavors in some cases, necessitating the search for efficient novel technologies. A wide range of microorganisms, including bacteria such as Lactobacillus acidophilus and Lactiplantibacillus plantarum, as well as fungi like Fusarium venenatum and Neurospora intermedia, have improved the product texture to mimic fibrous meat structures. Additionally, the chewiness and hardness of the resulting meat analogs have been further improved through the use of Bacillus subtilis. However, excessive fermentation may result in a decrease in the final product's firmness and produce a slimy texture. Similarly, several microbial metabolites can mimic the color and flavor of meat, with some concerns. It appears that fermentation is a promising approach to modulating the sensory profiles of plant-derived meat ingredients without adverse consequences. In addition, the technology of starter cultures can be optimized and introduced as a new strategy to enhance the organoleptic properties of plant-based meat while still meeting the needs of an expanding and sustainable economy.

High moisture extrusion of plant proteins: advances, challenges, and opportunities.

High moisture extrusion is a widely used technology for producing fibrous meat analogues in an efficient and scalable manner. Extrusion of soy, wheat gluten, and pea is well-documented and related products are already available in the market. There has been growing interest to diversify the protein sources used for meat analogues due to concerns over food waste, monocropping and allergenicity. Optimizing the extrusion process for plant proteins (e.g., hemp, mung bean, fava bean) tends to be time consuming and relies on the operators' intuition and experience to control the process well. Simulating the extrusion process has been challenging so far due to the diverse inputs and configurations involved during extrusion. This review details the mechanism for fibrous structure formation and provides an overview of the extrusion parameters used for texturizing a broad range of plant protein sources. Referring to these data reduces the resources needed for optimizing the extrusion process for novel proteins and may be useful for future extrusion modeling efforts. The review also highlights potential challenges and opportunities for extruding plant proteins, which may help to accelerate the development and commercialization of related products.

Significance of Fermentation in Plant-Based Meat Analogs: A Critical Review of Nutrition, and Safety-Related Aspects.

Plant-based meat analogs have been shown to cause less harm for both human health and the environment compared to real meat, especially processed meat. However, the intense pressure to enhance the sensory qualities of plant-based meat alternatives has caused their nutritional and safety aspects to be overlooked. This paper reviews our current understanding of the nutrition and safety behind plant-based meat alternatives, proposing fermentation as a potential way of overcoming limitations in these aspects. Plant protein blends, fortification, and preservatives have been the main methods for enhancing the nutritional content and stability of plant-based meat alternatives, but concerns that include safety, nutrient deficiencies, low digestibility, high allergenicity, and high costs have been raised in their use. Fermentation with microorganisms such as Bacillus subtilis, Lactiplantibacillus plantarum, Neurospora intermedia, and Rhizopus oryzae improves digestibility and reduces allergenicity and antinutritive factors more effectively. At the same time, microbial metabolites can boost the final product's safety, nutrition, and sensory quality, although some concerns regarding their toxicity remain. Designing a single starter culture or microbial consortium for plant-based meat alternatives can be a novel solution for advancing the health benefits of the final product while still fulfilling the demands of an expanding and sustainable economy.

Tetramethylphosphinane as a new secondary phosphine synthon.

Secondary phosphines are important building blocks in organic chemistry as their reactive P-H bond enables construction of more elaborate molecules. In particular, they can be used to construct tertiary phosphines that have widespread applications as organocatalysts, and as ligands in metal-complex catalysis. We report here a practical synthesis of the bulky secondary phosphine synthon 2,2,6,6-tetramethylphosphinane (TMPhos). Its nitrogen analogue tetramethylpiperidine, known for over a century, is used as a base in organic chemistry. We obtained TMPhos on a multigram scale from an inexpensive air-stable precursor, ammonium hypophosphite. TMPhos is also a close structural relative of di-tert-butylphosphine, a key component of many important catalysts. Herein we also describe the synthesis of key derivatives of TMPhos, with potential applications ranging from CO2 conversion to cross-coupling and beyond. The availability of a new core phosphine building block opens up a diverse array of opportunities in catalysis.

Iterative Supervised Principal Component Analysis Driven Ligand Design for Regioselective Ti-Catalyzed Pyrrole Synthesis.

The rational design of catalysts remains a challenging endeavor within the broader chemical community owing to the myriad variables that can affect key bond-forming events. Designing selective catalysts for any reaction requires an efficient strategy for discovering predictive structure-activity relationships. Herein, we describe the use of iterative supervised principal component analysis (ISPCA) in de novo catalyst design. The regioselective synthesis of 2,5-dimethyl-1,3,4-triphenyl-1H-pyrrole (C) via a Ti-catalyzed formal [2 + 2 +1] cycloaddition of phenylpropyne and azobenzene was targeted as a proof of principle. The initial reaction conditions led to an unselective mixture of all possible pyrrole regioisomers. ISPCA was conducted on a training set of catalysts, and their performance was regressed against the scores from the top three principal components. Component loadings from this PCA space and k-means clustering were used to inform the design of new test catalysts. The selectivity of a prospective test set was predicted in silico using the ISPCA model, and optimal candidates were synthesized and tested experimentally. This data-driven predictive-modeling workflow was iterated, and after only three generations the catalytic selectivity was improved from 0.5 (statistical mixture of products) to over 11 (>90% C) by incorporating 2,6-dimethyl-4-(pyrrolidin-1-yl)pyridine as a ligand. The origin of catalyst selectivity was probed by examining ISPCA variable loadings in combination with DFT modeling, revealing that ligand lability plays an important role in selectivity. A parallel catalyst search using multivariate linear regression (MLR), a popular approach in catalysis informatics, was also conducted in order to compare these strategies in a hypothetical catalyst scouting campaign. ISPCA appears to be more robust and predictive than MLR when sparse training sets are used that are representative of the data available during the early search for an optimal catalyst. The successful development of a highly selective catalyst without resorting to long, stochastic screening processes demonstrates the inherent power of ISPCA in de novo catalyst design and should motivate the general use of ISPCA in reaction development.

Dative Directing Group Effects in Ti-Catalyzed [2+2+1] Pyrrole Synthesis: Chemo- and Regioselective Alkyne Heterocoupling.

Transient dative substrate-Ti interactions have been found to play a key role in controlling the regioselectivity of alkyne insertion and [2+2] cycloaddition in Ti-catalyzed [2+2+1] pyrrole synthesis and Ti-catalyzed alkyne hydroamination. TMS-protected alkynes with pendent Lewis basic groups can invert the regioselectivity of TMS-protected alkyne insertion, leading to the selective formation of highly substituted 3-TMS pyrroles. The competency of various potential directing groups was investigated, and it was found that the directing-group effect can be tuned by modifying the catalyst Lewis acidity, the directing-group basicity, or the directing-group tether length. Dative directing-group effects are unexplored with Ti catalysts, and this study demonstrates the potential power of dative substrate-Ti interactions in tuning selectivity.

Modern applications of low-valent early transition metals in synthesis and catalysis.

Low-valent early transition metals are often intrinsically highly reactive as a result of their strong propensity toward oxidation to more stable high-valent states. Harnessing these highly reducing complexes for productive reactivity is potentially powerful for C-C bond construction, organic reductions, small-molecule activation and many other reactions that offer orthogonal chemoselectivity and/or regioselectivity patterns to processes promoted by late transition metals. Recent years have seen many exciting new applications of low-valent metals through building new catalytic and/or multicomponent reaction manifolds out of classical reactivity patterns. In this Review, we survey new methods that employ early transition metals and invoke low-valent precursors or intermediates in order to identify common themes and strategies in synthesis and catalysis.

Assessment of the risk posed to Singapore by the emergence of artemisinin-resistant malaria in the Greater Mekong Subregion

Objective@#To assess the public health risk to Singapore posed by the emergence of artemisinin-resistant (ART-R) malaria in the Greater Mekong Subregion (GMS).@*Methods@#We assessed the likelihood of importation of drug-resistant malaria into Singapore and the impact on public health of its subsequent secondary spread in Singapore. Literature on the epidemiology and contextual factors associated with ART-R malaria was reviewed. The epidemiology of malaria cases in Singapore was analysed. The vulnerability and receptivity of Singapore were examined, including the connectivity with countries reporting ART-R malaria, as well as the preparedness of Singaporean health authorities. Sources of information include international journals, World Health Organization guidelines, data from the Singapore Ministry of Health and National Public Health Laboratory of the National Centre for Infectious Diseases, and the International Air Transport Association.@*Results@#The importation of ART-R malaria into Singapore is possible given the close proximity and significant travel volume between Singapore and the GMS countries reporting artemisinin resistance. Singapore’s vulnerability is further enhanced by the presence of foreign workers from neighbouring endemic countries. Nonetheless, the overall likelihood of such an event is low based on the rarity and decreasing trend of imported malaria incidence. With the presence of Anopheles vectors in Singapore, imported cases of drug-resistant malaria could cause secondary transmission. Nevertheless, the risk of sustained spread is likely to be mitigated by the comprehensive surveillance and control system in place for both infected vectors and human cases.@*Discussion@#This risk assessment highlights the need for a continued high degree of vigilance of ART-R malaria locally and globally to minimize the risk and public health impact of drug-resistant malaria in Singapore.

Oxidative nitrene transfer from azides to alkynes via Ti(ii)/Ti(iv) redox catalysis: formal [2+2+1] synthesis of pyrroles.

Catalytic oxidative nitrene transfer from azides with the early transition metals is rare, and has not been observed without the support of redox noninnocent spectator ligands. Here, we report the formal [2+2+1] coupling of azides and alkynes via TiII/TiIV redox catalysis from simple Ti halide imido precatalysts. These reactions yield polysubstituted N-alkyl pyrroles, including N-benzyl protected pyrroles and rare examples of very electron rich pentaalkyl pyrroles. Mechanistic analysis reveals that [2+2+1] reactions with bulky azides have different mechanistic features from previously-reported reactions using azobenzene as a nitrene source.

Diverse Reactivity of Diazatitanacyclohexenes: Coupling Reactions of 2H-Azirines Mediated by Titanium(II).

2H-Azirines are versatile coupling partners for the synthesis of N-heterocycles. Herein, we present our studies on the reactivity of Cp2Ti(BTMSA) (1; BTMSA = bis(trimethylsilyl)acetylene) with a variety of azirines. In all the cases examined, the initial organometallic products formed are diazatitanacyclohexenes, presumably formed via oxidative addition of Ti(II) into the C-N bond of the azirine to form an azatitanacyclobutene intermediate, followed by C═N insertion of a second equivalent of azirine into the Ti-C bond to form the observed products. Diazatitanacyclohexene 3, bearing phenyl substituents and derived from 2,3-diphenyl-2H-azirine, fragments to form an azabutadiene and nitrile, which is shown to be catalytic in the presence of excess 2,3-diphenyl-2H-azirine. H-substituted complex 8, derived from 3-phenyl-2H-azirine, decomposes via protonolysis of the Cp ligands. In contrast, the methyl-substituted diazatitanacyclohexene 10, derived from 2-methyl-3-phenyl-2H-azirine, is thermally robust. Attempts to trap the putative azatitanacyclobutene intermediate with an alkyne were unsuccessful, resulting instead in the formation of titanacyclopentadiene (12) from coupling of alkyne with BTMSA. Initial reactivity studies found that 10 could be protonolyzed with AcOH to form mixtures of pyrrole and aziridine products, whereas reacting 10 with MeOH results solely in the formation of 2,4-dimethyl-3,5-diphenyl-1H-pyrrole.

Generation of TiII Alkyne Trimerization Catalysts in the Absence of Strong Metal Reductants.

Low-valent TiII species have typically been synthesized by the reaction of TiIV halides with strong metal reductants. Herein we report that TiII species can be generated simply by reacting TiIV imido complexes with 2 equiv of alkyne, yielding a metallacycle that can reductively eliminate pyrrole while liberating TiII. In order to probe the generality of this process, TiII-catalyzed alkyne trimerization reactions were carried out with a diverse range of TiIV precatalysts.