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Molecules (Basel, Switzerland) Jul 2022Three events occurred in the second half of 1946 in three adjoining US States (NJ, NY, and PA) which marked the birth of Hydrosilylation Technology. They occurred before... (Review)
Review
Three events occurred in the second half of 1946 in three adjoining US States (NJ, NY, and PA) which marked the birth of Hydrosilylation Technology. They occurred before the landmark 1957 JACS paper and the 1958 issued US patent by Speier et al. and before Chalk and Harrod named the reaction. First, on 27 June 1946, Mackenzie et al., of Montclair Research Corp., applied for a patent to prepare addition compounds of hydridosilanes and unsaturated organic compounds. Then, on 9 October 1946, Wagner and Strother of Union Carbide Corp. applied for a patent on a process to produce organic compounds of silicon with Si-C bonds by reacting a hydridosilane and an alkene or alkyne in the presence of a catalyst metal of the platinum group. Finally, Sommer et al., submitted a paper on peroxide-catalyzed hydrosilylation to JACS on 17 December 1946. It was published in January 1947. The landmark patent interference and priority case law associated with the Mackenzie et al. and Wagner et al., applications is well known to patent attorneys. This presentation will retrace the origins of hydrosilylation and report events (1946-1960) in the history of the reaction that are most probably unknown to most authors and presenters of hydrosilylation investigations. George Wagner's contribution to the birth of this technology is also highlighted.
Topics: Alkenes; Alkynes; Catalysis; Silicon
PubMed: 35889213
DOI: 10.3390/molecules27144341 -
Molecules (Basel, Switzerland) Sep 2022A one-pot synthesis of linear and cyclic β-alkoxyselenides is developed through the iodine-mediated three-component reaction of elemental selenium with alkenes (dienes)...
A one-pot synthesis of linear and cyclic β-alkoxyselenides is developed through the iodine-mediated three-component reaction of elemental selenium with alkenes (dienes) and alcohols. Selenylation of 1,5-hexadiene gives 2,5-di(methoxymethyl)tetrahydroselenophene and 2-methoxy-6-(methoxymethyl)tetrahydro-2-selenopyran via the 5 and 6- cyclization. 1,7-Octadiene affords only linear 1:2 adduct with two terminal double bonds. 1,5-Cyclooctadiene results in one diastereomer of 2,6-dialkoxy-9-selenabicyclo [3.3.1]nonanes via 6- cyclization. With 1,3-diethenyl-1,1,3,3-tetramethyldisiloxane, the first ring-substituted representative of a very rare class of heterocycles, 1,4,2,6-oxaselenadisilinanes, was obtained at a high yield.
Topics: Alcohols; Alkenes; Cyclization; Iodine; Polyenes; Selenium
PubMed: 36234704
DOI: 10.3390/molecules27196169 -
Angewandte Chemie (International Ed. in... Jan 2023A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized...
A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized products. The process allows E,Z-mixed dienes to be processed to a single E-alkene isomer, and leverages an inexpensive and operationally convenient I(I)/I(III) catalysis platform. The first example of catalytic 1,4-difluorination is disclosed and subsequently evolved to enable 1,4-hetero-difunctionalization, which allows δ-fluoro-alcohol and amine derivatives to be forged in a single operation. The protocol is compatible with a variety of nucleophiles including fluoride, nitriles, carboxylic acids, alcohols and even water thereby allowing highly functionalized products, with a stereocenter bearing both C(sp )-F and C(sp )-CF groups, to be generated rapidly. Scalability (up to 3 mmol), and facile post-reaction modifications are demonstrated to underscore the utility of the method in expanding organofluorine chemical space.
Topics: Polyenes; Isomerism; Alkenes; Catalysis; Alcohols
PubMed: 36345795
DOI: 10.1002/anie.202214906 -
Journal of Industrial Microbiology &... May 2017Advancement in metabolic engineering of microorganisms has enabled bio-based production of a range of chemicals, and such engineered microorganism can be used for... (Review)
Review
Advancement in metabolic engineering of microorganisms has enabled bio-based production of a range of chemicals, and such engineered microorganism can be used for sustainable production leading to reduced carbon dioxide emission there. One area that has attained much interest is microbial hydrocarbon biosynthesis, and in particular, alkanes and alkenes are important high-value chemicals as they can be utilized for a broad range of industrial purposes as well as 'drop-in' biofuels. Some microorganisms have the ability to biosynthesize alkanes and alkenes naturally, but their production level is extremely low. Therefore, there have been various attempts to recruit other microbial cell factories for production of alkanes and alkenes by applying metabolic engineering strategies. Here we review different pathways and involved enzymes for alkane and alkene production and discuss bottlenecks and possible solutions to accomplish industrial level production of these chemicals by microbial fermentation.
Topics: Alkanes; Alkenes; Biofuels; Fatty Acids; Fermentation; Metabolic Engineering
PubMed: 27565672
DOI: 10.1007/s10295-016-1814-y -
Accounts of Chemical Research Mar 2021The development of novel synthetic methods remains a cornerstone in simplifying complex molecule synthesis. Progress in the field of transition metal catalysis has... (Review)
Review
The development of novel synthetic methods remains a cornerstone in simplifying complex molecule synthesis. Progress in the field of transition metal catalysis has enabled new mechanistic strategies to achieve difficult chemical transformations, increased the value of abundant chemical building blocks, and pushed the boundaries of creative and strategic route design to improve step economy in multistep synthesis. Methodologies to introduce an olefin into saturated molecules continue to be essential transformations because of the plethora of reactions available for alkene functionalization. Of particular importance are dehydrogenation reactions adjacent to electron-withdrawing groups such as carbonyls, which advantageously provide activated olefins that can be regioselectively manipulated. Palladium catalysis occupies a central role in the most widely adopted carbonyl dehydrogenation reactions, but limits to the scope of these protocols persist.In this Account, we describe our group's contributions to the area of transition-metal-catalyzed dehydrogenation using palladium catalysis and more sustainable and economical nickel catalysis. These metals are used in conjunction with allyl and aryl halides or pseudohalides that serve as oxidants to access a unique mechanistic approach for one-step α,β-dehydrogenation of various electron-withdrawing groups, including ketones, esters, nitriles, amides, carboxylic acids, and electron-deficient heteroarenes. The pivotal reaction parameters that can be modified to influence reaction efficiency are highlighted, including base and oxidant structure as well as ligand and salt additive effects. This discussion is expected to serve as a guide for troubleshooting challenging dehydrogenation reactions and provide insight for future reaction development in this area.In addition to enabling dehydrogenation reactions, our group's allyl-Pd and -Ni chemistry can be used for C-C and C-X bond-forming reactions, providing novel disconnections with practical applications for expediting multistep synthesis. These transformations include a telescoped process for ketone α,β-vicinal difunctionalization; an oxidative enone β-functionalization, including β-stannylation, β-silylation, and β-alkylation; and an oxidative cycloalkenylation between unstabilized ketone enolates and unactivated alkenes. These bond-forming methodologies broaden the range of transformations accessible from abundant ketone, enone, and alkene moieties. Both the dehydrogenation and C-C and C-X bond-forming methodologies have been implemented in our group's total synthesis campaigns to provide step-efficient synthetic routes toward diverse natural products.Through the lens of multistep synthesis, the utility and robustness of our dehydrogenation and dehydrogenative functionalization methodologies can be better appreciated, and we hope that this Account will inspire practitioners to apply our methodologies to their own synthetic challenges.
Topics: Alkenes; Catalysis; Hydrogenation; Ketones; Molecular Structure; Nickel; Palladium; Stereoisomerism
PubMed: 33592147
DOI: 10.1021/acs.accounts.0c00787 -
Nature Communications Apr 2022Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation...
Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation method applied to a broad range of unactivated alkenes remains challenging. Herein, we report a NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes to access β- or γ-branched alkyl carboxylic acids and β-, γ- or δ-branched alkyl amines. A broad range of alkyl iodides and bromides with different functional groups can be installed with excellent regiocontrol and availability for site-selective late-stage functionalization of biorelevant molecules. Under modified reaction conditions with NiCl(PPh) as the catalyst, migratory hydroalkylation takes place to provide β- (rather than γ-) branched products. The keys to success are the use of aminoquinoline and picolinamide as suitable directing groups and combined experimental and computational studies of ligand effects on the regioselectivity and detailed reaction mechanisms.
Topics: Alkenes; Bromides; Catalysis; Iodides; Ligands
PubMed: 35393419
DOI: 10.1038/s41467-022-29554-4 -
Journal of the American Chemical Society Apr 2022The therapeutic properties of (ginger and turmeric's family) have long been known in traditional medicine. However, only recently have guaiane-type sesquiterpenes...
The therapeutic properties of (ginger and turmeric's family) have long been known in traditional medicine. However, only recently have guaiane-type sesquiterpenes extracted from been submitted to biological testing, and their enhanced bioactivity was highlighted. Among these compounds, phaeocaulisin A has shown remarkable anti-inflammatory and anticancer activity, which appears to be tied to the unique bridged acetal moiety embedded in its tetracyclic framework. Prompted by the promising biological profile of phaeocaulisin A and by the absence of a synthetic route for its provision, we have implemented the first enantioselective total synthesis of phaeocaulisin A in 17 steps with 2% overall yield. Our route design builds on the identification of an enantioenriched lactone intermediate, tailored with both a ketone moiety and a conjugated alkene system. Taking advantage of the umpolung carbonyl-olefin coupling reactivity enabled by the archetypal single-electron transfer (SET) reductant samarium diiodide (SmI), the lactone intermediate was submitted to two sequential SmI-mediated cyclizations to stereoselectively construct the polycyclic core of the natural product. Crucially, by exploiting the innate inner-sphere nature of carbonyl reduction using SmI, we have used a steric blocking strategy to render sites SET-unreceptive and thus achieve chemoselective reduction in a complex substrate. Our asymmetric route enabled elucidation of the naturally occurring isomer of phaeocaulisin A and provides a synthetic platform to access other guaiane-type sesquiterpenes from ─as well as their synthetic derivatives─for medicinal chemistry and drug design.
Topics: Alkenes; Cyclization; Electron Transport; Lactones; Sesquiterpenes, Guaiane
PubMed: 35417150
DOI: 10.1021/jacs.2c02188 -
Angewandte Chemie (International Ed. in... Aug 2022Vinylbenziodoxolones have recently been identified as efficient hypervalent iodine(III) reagents for electrophilic vinylations under transition metal-free conditions....
Vinylbenziodoxolones have recently been identified as efficient hypervalent iodine(III) reagents for electrophilic vinylations under transition metal-free conditions. Their unique reactivity allows synthesis of either internal or terminal alkenes, depending on the nucleophile class. This paper constitutes the first mechanistic investigation of VBX vinylations, and makes use of NMR studies, deuterium labelling and computations to rationalize the observed regio- and stereochemical outcome. Internal alkene formation in S-vinylation was found to proceed through the ligand coupling mechanism typical of diaryliodonium salts, whereas terminal alkene formation in P-vinylations took place via a phosphinous acid-coordinated VBX complex, which underwent concerted deprotonation and Michael-type addition. Subsequent base-assisted protonation and E2 elimination delivered the terminal alkene. The findings can be used to predict the regioselectivity in vinylations of other nucleophile classes.
Topics: Alkenes; Catalysis; Iodine; Ligands
PubMed: 35748793
DOI: 10.1002/anie.202206347 -
Nature Chemistry Jun 2022Many therapeutic agents are macrocyclic trisubstituted alkenes but preparation of these structures is typically inefficient and non-selective. A possible solution would...
Many therapeutic agents are macrocyclic trisubstituted alkenes but preparation of these structures is typically inefficient and non-selective. A possible solution would entail catalytic macrocyclic ring-closing metathesis, but these transformations require high catalyst loading, conformationally rigid precursors and are often low yielding and/or non-stereoselective. Here we introduce a ring-closing metathesis strategy for synthesis of trisubstituted macrocyclic olefins in either stereoisomeric form, regardless of the level of entropic assistance. The goal was achieved by addressing several unexpected difficulties, including complications arising from pre-ring-closing metathesis alkene isomerization. The power of the method is highlighted by two examples. The first is the near-complete reversal of substrate-controlled selectivity in the formation of a macrolactam related to an antifungal natural product. The other is a late-stage stereoselective generation of an E-trisubstituted alkene in a 24-membered ring, en route to the cytotoxic natural product dolabelide C.
Topics: Alkenes; Biological Products; Catalysis; Cyclization; Stereoisomerism
PubMed: 35577918
DOI: 10.1038/s41557-022-00935-y -
Journal of the American Chemical Society Jun 2022We report a total synthesis of the alkaloid myrioneurinol enabled by the recognition of hidden symmetry within its polycyclic structure. Our approach traces...
We report a total synthesis of the alkaloid myrioneurinol enabled by the recognition of hidden symmetry within its polycyclic structure. Our approach traces myrioneurinol's complex framework back to a symmetrical diketone precursor, a double reductive amination of which forges its central piperidine unit. By employing an inexpensive chiral amine in this key desymmetrizing event, four stereocenters of the natural product including the core quaternary stereocenter are set in an absolute sense, providing the first asymmetric entry to this target. Other noteworthy strategic maneuvers include utilizing a bicyclic alkene as a latent -1,3-bis(hydroxymethyl) synthon and a topologically controlled alkene hydrogenation. Overall, our synthesis proceeds in 18 steps and ∼1% yield from commercial materials.
Topics: Alkaloids; Alkenes; Amination; Heterocyclic Compounds, 4 or More Rings; Stereoisomerism
PubMed: 35699935
DOI: 10.1021/jacs.2c04487