Rhodium‐Catalyzed Remote C(sp3)−H Borylation of Silyl Enol Ethers

A rhodium‐catalyzed remote C(sp³)?H borylation of silyl enol ethers (SEEs, E/Z mixtures) by alkene isomerization and hydroboration is reported. The reaction exhibits mild reaction conditions and excellent functional‐group tolerance. This method is compatible with an array of SEEs, including linear and branched SEEs derived from aldehydes and ketones, and provides direct access to a broad range of structurally diverse 1,n‐borylethers in excellent regioselectivities and good yields. These compounds are precursors to various valuable chemicals, such as 1,n‐diols and aminoalcohols.     

Unprecedented Cobalt‐Catalyzed Isomerization Reactions to Single Skipped 2,4,7‐Trienes Applied in the Synthesis of Urushiol

The cobalt‐catalyzed isomerization of 1,3‐dienes to 2Z,4E‐dienes was realized for the very challenging substrates with an additional double bond in the side chain. An isomerization to the conjugated 3,5,7‐triene derivative was not observed, which is in stark contrast to observations with many other isomerization catalysts. Accordingly, the synthesis of the natural product urushiol, which has a sensitive 2Z,4E,7Z‐triene subunit in the side chain, was investigated. The O‐protected urushiol derivative was generated selectively without isomerization to the conjugated 3,5,7‐triene or Z/E‐isomerization of the double bond at position 7.     

Organic Base‐Catalyzed Stereoselective Isomerizations of 4‐Hydroxy‐4‐phenyl‐but‐2‐ynoic Acid Methyl Ester to (E)‐ and (Z)‐4‐Oxo‐4‐phenyl‐but‐2‐enoic Acid Methyl Esters

We have developed a 1,4‐diazabicyclo[2.2.2]octane (DABCO)‐catalyzed isomerization of 4‐hydroxy‐4‐phenyl‐but‐2‐ynoic acid methyl ester to (E)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester and an N,N‐diisopropylethylamine‐catalyzed isomerization of the same substrate to (Z)‐4‐oxo‐4‐phenyl‐but‐2‐enoic acid methyl ester.     

Light‐Mediated Total Synthesis of 17‐Deoxyprovidencin

An asymmetric synthesis of the diterpenoid 17‐deoxyprovidencin is described. Key steps include an aldol addition, a base‐catalyzed Wipf‐type furan formation, a Z‐selective ring‐closing metathesis for macrocyclization, a photochemical E/Z isomerization to a highly strained and conformationally restricted ring system, and the stereoselective formation of two epoxides on the ring.     

Enantioselective Synthesis of Chiral Cyclopent‐2‐enones by Nickel‐Catalyzed Desymmetrization of Malonate Esters

The enantioselective synthesis of highly functionalized chiral cyclopent‐2‐enones by the reaction of alkynyl malonate esters with arylboronic acids is described. These desymmetrizing arylative cyclizations are catalyzed by a chiral phosphinooxazoline/nickel complex, and cyclization is enabled by the reversible E/Z isomerization of alkenylnickel species. The general methodology is also applicable to the synthesis of 1,6‐dihydropyridin‐3(2H)‐ones.     

(E/Z)‐Isomerization of (all‐E)‐5,6‐Diepikarpoxanthin

(all‐E)‐5,6‐Diepikarpoxanthin (=(all‐E,3S,5S,6S,3′R)‐5,6‐dihydro‐β,β‐carotene‐3,5,6,3′‐tetrol; 1 ) was submitted to thermal isomerization and I₂‐catalyzed photoisomerization. The structures of the main products, i.e. (9Z)‐ ( 2 ), (9′Z)‐ ( 3 ), (13Z)‐ ( 4 ), (13′Z)‐ ( 5 ), and (15Z)‐5,6‐diepikarpoxanthin ( 6 ), were determined by their UV/VIS, CD, ¹H‐NMR, and mass spectra. In addition, (9Z,13′Z)‐ or (13Z,9′Z)‐ ( 7 ), (9Z,9′Z)‐ ( 8 ), and (9Z,13Z)‐ or (9′Z,13′Z)‐5,6‐diepikarpoxanthin ( 9 ) were tentatively identified as minor products of the I₂‐catalyzed photoisomerization.     

Stereocontrolled Synthesis of Benzo[k]fluoranthenes—An Unexpected Isomerization Mediated by Rhodacyclopentadiene

Herein, a Rh^III‐catalyzed stereocontrolled synthesis of benzo[k]fluoranthenes is reported. It was found that the unexpected E/Z isomerization was highly sensitive to the electronic effects of the substituents on the aryl groups. Theoretical calculations revealed that this controllable stereochemistry originates from the mediation of rhodacyclopentadiene intermediates during the isomerization. The fact that similar stereochemistry was observed when using an Ir^III catalyst further suggests a certain generality of this discovery toward some other transition metals.     

(E/Z)‐Isomerization of 3′‐Epilutein

3′‐Epilutein (=(all‐E,3R,3′S,6′R)‐4′,5′‐didehydro‐5′,6′‐dihydro‐β,β‐carotene‐3,3′‐diol; 1 ), isolated from the flowers of Caltha palustris, was submitted to both thermal isomerization and I₂‐catalyzed photoisomerization. The structures of the main products (9Z)‐ 1 , (9′Z)‐ 1 , (13Z)‐ 1 , (13′Z)‐ 1 , (15Z)‐ 1 , and (9Z,9′Z)‐ 1 were determined based on UV/VIS, CD, ¹H‐NMR, and MS data.     

E/Z Oxime Isomerism in PhC(NOH)CN

The reaction of nitric oxide with benzyl cyanide in the presence of potassium methoxide at low temperature gave the dipotassium salt of a bis‐diazeniumdiolate 2 in excellent yield. Two new stereospecific syntheses of E or Z 2‐(hydroxyimino)‐2‐phenylacetonitrile from 2 have been found. The thermodynamics of the E/Z isomerization has been investigated spectroscopically in solution, in the solid state by differential scanning calorimetry (DSC), and theoretically in the gas phase. Evidence of catalysis by NO of E/Z oxime isomerization has been observed.     

Polysubstituted 5‐Phenylazopyrimidines: Extremely Fast Non‐ionic Photochromic Oscillators

Photochromic systems with an ultrahigh rate of thermal relaxation are highly desirable for the development of new efficient photochromic oscillators. Based on DFT calculations, we designed a series of 5‐phenylazopyrimidines with strong push–pull character in silico and observed very low energy barriers for the thermal (Z)‐to‐(E) isomerization. The structure of the (Z)‐isomer of the slowest isomerizing derivative in the series was confirmed by NMR analysis with in situ irradiation at low temperature. The substituents can tune the lifetime of thermal back isomerization from hundreds of microseconds to several nanoseconds (8 orders of magnitude). The photoswitching parameters were extracted from transient absorption techniques and a dominant rotation mechanism of the (Z)‐to‐(E) thermal fading was proposed based on DFT calculations.     

One‐Pot Synthesis of (−)‐Oseltamivir and Mechanistic Insights into the Organocatalyzed Michael Reaction

The one‐pot sequential synthesis of (?)‐oseltamivir has been achieved without evaporation or solvent exchange in 36 % yield over seven reactions. The key step was the asymmetric Michael reaction of pentan‐3‐yloxyacetaldehyde with (Z)‐N‐2‐nitroethenylacetamide, catalyzed by a diphenylprolinol silyl ether. The use of a bulky O‐silyl‐substituted diphenylprolinol catalyst, chlorobenzene as a solvent, and HCO₂H as an acid additive, were key to produce the first Michael adduct in both excellent yield and excellent diastereo‐ and enantioselectivity. Investigation into the effect of acid demonstrated that an acid additive accelerates not only the E–Z isomerization of the enamines derived from pentan‐3‐yloxyacetaldehyde with diphenylprolinol silyl ether, but also ring opening of the cyclobutane intermediate and the addition reaction of the enamine to (Z)‐N‐2‐nitroethenylacetamide. The transition‐state model for the Michael reaction of pentan‐3‐yloxyacetaldehyde with (Z)‐N‐2‐nitroethenylacetamide was proposed by consideration of the absolute configuration of the major and minor isomers of the Michael product with the results of the Michael reaction of pentan‐3‐yloxyacetaldehyde with phenylmaleimide and naphthoquinone.     

Contra‐Thermodynamic,Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two‐Dimensional Chemical Space

Designing strategies to access stereodefined olefinic organoboron species is an important synthetic challenge. Despite significant advances, there is a striking paucity of routes to Z‐α‐substituted styrenyl organoborons. Herein, this strategic imbalance is redressed by exploiting the polarity of the C(sp²)−B bond to activate the neighboring π system, thus enabling a mild, traceless photocatalytic isomerization of readily accessible E‐α‐substituted styrenyl BPins to generate the corresponding Z‐isomers with high fidelity. Preliminary validation of this contra‐thermodynamic E→Z isomerization is demonstrated in a series of stereoretentive transformations to generate Z‐configured trisubstituted alkenes, as well as in a concise synthesis of the anti‐tumor agent Combretastatin A4.     

Rhodium-Catalyzed Remote C(sp3)−H Borylation of Silyl Enol Ethers

A rhodium-catalyzed remote C(sp³)−H borylation of silyl enol ethers (SEEs, E/Z mixtures) by alkene isomerization and hydroboration is reported. The reaction exhibits mild reaction conditions and excellent functional-group tolerance. This method is compatible with an array of SEEs, including linear and branched SEEs derived from aldehydes and ketones, and provides direct access to a broad range of structurally diverse 1,n-borylethers in excellent regioselectivities and good yields. These compounds are precursors to various valuable chemicals, such as 1,n-diols and aminoalcohols.     

Contra‐Thermodynamic,Photocatalytic E→Z Isomerization of Styrenyl Boron Species: Vectors to Facilitate Exploration of Two‐Dimensional Chemical Space

Designing strategies to access stereodefined olefinic organoboron species is an important synthetic challenge. Despite significant advances, there is a striking paucity of routes to Z‐α‐substituted styrenyl organoborons. Herein, this strategic imbalance is redressed by exploiting the polarity of the C(sp²)?B bond to activate the neighboring π system, thus enabling a mild, traceless photocatalytic isomerization of readily accessible E‐α‐substituted styrenyl BPins to generate the corresponding Z‐isomers with high fidelity. Preliminary validation of this contra‐thermodynamic E→Z isomerization is demonstrated in a series of stereoretentive transformations to generate Z‐configured trisubstituted alkenes, as well as in a concise synthesis of the anti‐tumor agent Combretastatin A4.     

Influence of photoinduced isomerization on the chiral separation of novel liquid crystalline materials with a diazene moiety

The influence of photoinduced isomerization on the enantiomeric separation of two newly synthesized liquid crystalline materials, liquid crystals 1 and 2, was studied by high‐performance liquid chromatography on a chiral stationary phase Chiralpack AD‐3. Both materials have one chiral center and one diazene moiety. The compounds were separated into their E and Z isomeric forms. The conditions and time scale of the ultraviolet‐induced E to Z transition were briefly evaluated. Under the optimized conditions, we were able to baseline separate the S and R enantiomers of both the studied materials in their E isomeric form. The chiral separation of liquid crystal 2 after ultraviolet irradiation was unsuccessful. In contrast, the chiral separation of liquid crystal 1 possessing a similar structure to liquid crystal 2 provided baseline separation in its Z isomeric form as well. Previously, we have shown the influence of photoinduced isomerization and its utilization in the enantioseparation on relatively simple molecules. Here, we demonstrate that (1) much more complex compounds can also be successfully separated despite the bulkiness of the achiral part of the structure and (2) photoinduced isomerization even for such complex molecules still strongly influences their chromatographic properties.     

Migratory Hydrogenation of Terminal Alkynes by Base/Cobalt Relay Catalysis

Migratory functionalization of alkenes has emerged as a powerful strategy to achieve functionalization at a distal position to the original reactive site on a hydrocarbon chain. However, an analogous protocol for alkyne substrates is yet to be developed. Herein, a base and cobalt relay catalytic process for the selective synthesis of (Z)‐2‐alkenes and conjugated E alkenes by migratory hydrogenation of terminal alkynes is disclosed. Mechanistic studies support a relay catalytic process involving a sequential base‐catalyzed isomerization of terminal alkynes and cobalt‐catalyzed hydrogenation of either 2‐alkynes or conjugated diene intermediates. Notably, this practical non‐noble metal catalytic system enables efficient control of the chemo‐, regio‐, and stereoselectivity of this transformation.     

Selective Synthesis of Z‐Cinnamyl Ethers and Cinnamyl Alcohols through Visible Light‐Promoted Photocatalytic E to Z Isomerization

A photocatalytic E to Z isomerization of alkenes using an iridium photosensitizer under mild reaction conditions is disclosed. This method provides scalable and efficient access to Z‐cinnamyl ether and allylic alcohol derivatives in high yields with excellent stereoselectivity. Importantly, this method also provides a powerful strategy for the selective synthesis of Z‐magnolol and honokiol derivatives possessing potential biological activity.     

Photocatalyzed E→Z Contra-thermodynamic Isomerization of Vinyl Boronates with Binaphthol

The photocatalytic contra-thermodynamic E→Z isomerization of vinyl boronates by using a binaphthol catalyst is disclosed. The reaction, based on the transient formation of a suitable chromophore with a BINOL derivative as the catalyst, allowed geometrical isomerization in good-to-excellent Z/E ratio and excellent-to-quantitative yields. The mechanism of this E→Z contra-thermodynamic isomerization was studied, and the formation of a transient chromophore species is suggested.     

Stereoselective Synthesis of Trisubstituted Vinylboronates from Ketone Enolates Triggered by 1,3‐Metalate Rearrangement of Lithium Enolates

An unprecedented stereoselective synthesis of trisubstituted vinylboronates is reported to proceed by direct borylation of lithium ketone enolates under transition‐metal‐free conditions. The stereospecific C?O borylation of lithium enolates was triggered by a carbonyl‐induced 1,3‐metalate rearrangement via a C‐bound boron enolate. DFT calculations and control experiments revealed that the stereoselectivity is controlled by sterics. A variety of stereospecific trisubstituted vinylboronates, together with several tetrasubstituted vinylboronates, were conveniently synthesized with the newly developed methodology. Based on the transformation of stereospecific vinylboronate, a single isomer of Dienestrol was efficiently obtained.     

2‐(4′‐Pyridyl‐N‐oxide)‐Substituted Hemithioindigos as Photoresponsive Guests for a Super Aryl‐Extended Calix[4]pyrrole Receptor

We report the synthesis of two 2‐(4′‐pyridyl‐N‐oxide)‐substituted hemithioindigos (HTIs). We probed their photoisomerization by using UV/Vis and ¹H NMR spectroscopy techniques. Light irradiation at λ=450 nm provoked the isomerization of the HTI Z isomer to the E counterpart to a large extent (≈80 % at the photostationary state). ¹H NMR titration experiments revealed the formation of thermodynamically and kinetically stable 1:1 inclusion complexes of the (Z)‐HTI isomers with a super aryl‐extended host (association constant>10⁴ m ^?1). Photoirradiation at λ=450 nm of the inclusion complexes induced the isomerization of the bound HTI N‐oxide to afford the (E)‐HTI?calix[4]pyrrole complex. We determined accurate association constant values for the 1:1 inclusion complexes of the (Z)‐ and (E)‐HTI isomers by using isothermal titration calorimetry experiments. The results showed that the stability constants of the (E)‐HTI complexes were 2.2–2.8‐fold lower than those of the (Z)‐HTI counterparts, which explains the lack of light‐induced release of the former to the bulk solution.