Total Synthesis of (-)-Antroalbocin A Enabled by a Strain Release-Controlled Photochemical 1,3-Acyl Shift.

The first bioinspired, enantioselective, and protecting group free total synthesis of the antibacterial sesquiterpenoid (-)-antroalbocin A (1) has been achieved in 12 steps (5.4% overall yield) from dimedone. An organocatalytic Robinson annulation gave rapid access to the tricyclic enone (19) as starting material for the photochemical domino process of deconjugation and sigmatropic 1,3-acyl shift. Computational data of this process indicate that the 1,3-acyl shift benefits from the highly strained 1,3-enone 8. The transformation of 8 to its bridged isomer 5 is exergonic and, therefore, enables an increased conversion compared to unstrained substrates.

Equilibrating parent aminomercaptocarbene and CO2 with 2-amino-2-thioxoacetic acid via heavy-atom quantum tunneling.

The search for methods to bind CO2 and use it synthetically as a C1-building block under mild conditions is an ongoing endeavor of great urgency. The formation of heterocyclic carbene-carbon dioxide adducts occurs rapidly when the carbene is generated in solution in the presence of CO2. Here we demonstrate the reversible formation of a complex of the hitherto unreported aminomercaptocarbene (H2N-C̈-SH) with CO2 isolated in solid argon by photolysis of 2-amino-2-thioxoacetic acid. Remarkably, the complex disappears in the dark as deduced by time-dependent matrix infrared measurements, and equilibrates back to the covalently bound starting material. This kinetically excluded process below ca. 8 K is made possible through heavy-atom quantum mechanical tunneling, as also evident from density functional theory and ab initio computations at the CCSD(T)/cc-pVTZ level of theory. Our results provide insight into CO2 activation using a carbene and emphasize the role of quantum mechanical tunneling in organic processes, even involving heavy atoms.

Aminohydroxymethylene (H2N-C̈-OH), the Simplest Aminooxycarbene.

We generated and isolated hitherto unreported aminohydroxymethylene (1, aminohydroxycarbene) in solid Ar via pyrolysis of oxalic acid monoamide (2). Astrochemically relevant carbene 1 is persistent under cryogenic conditions and only decomposes to HNCO + H2 and NH3 + CO upon irradiation of the matrix at 254 nm. This photoreactivity is contrary to other hydroxycarbenes and aminomethylene, which undergo [1,2]H shifts to the corresponding carbonyls or imine. The experimental data are well supported by the results of CCSD(T)/cc-pVTZ and B3LYP/6-311++G(3df,3pd) computations.

Ethynylhydroxycarbene (H-C≡C-C̈-OH).

The species on the C3H2O potential energy surface have long been known to play a vital role in extraterrestrial chemistry. Here we report on the hitherto uncharacterized isomer ethynylhydroxycarbene (H-C≡C-C̈-OH, 1) generated by high-vacuum flash pyrolysis of ethynylglyoxylic acid ethyl ester and trapped in solid argon matrices at 3 and 20 K. Upon irradiation at 436 nm trans-1 rearranges to its higher lying cis-conformer. Prolonged irradiation leads to the formation of propynal. When the matrix is kept in the dark, 1 reacts within a half-life of ca. 70 h to propynal in a conformer-specific [1,2]H-tunneling process. Our results are fully consistent with computations at the CCSD(T)/cc-pVTZ and the B3LYP/def2-QZVPP levels of theory.

Characterization of the Simplest Thiolimine: The Higher Energy Tautomer of Thioformamide.

As sulfur-containing organic molecules thioamides and their isomers are conceivable intermediates in prebiotic chemistry, for example, in the formation of amino acids and thiazoles and resemble viable candidates for detection in interstellar media. Here, we report the characterization of parent thioformamide in the solid state via single-crystal X-ray diffraction and its photochemical interconversion to its hitherto unreported higher energy tautomer thiolimine in inert argon and dinitrogen matrices. Upon photogeneration, four conformers of thiolimine form, whose ratio depends on the employed wavelength. One of these conformers interconverts due to quantum mechanical tunneling with a half-life of 30-45 min in both matrix materials at 3 and 20 K. A spontaneous reverse reaction from thiolimine to thioformamide is not observed. To support our experimental findings, we explored the potential energy surface of the system at the AE-CCSD(T)/aug-cc-pCVTZ level of theory and computed tunneling half-lives with the CVT/SCT approach applying DFT methods.

Identification and Reactivity of s-cis,s-cis-Dihydroxycarbene, a New [CH2O2] Intermediate.

We report the first preparation of the s-cis,s-cis conformer of dihydroxycarbene (1cc) by means of pyrolysis of oxalic acid, isolation of the lower-energy s-trans,s-trans (1tt) and s-cis,s-trans (1ct) product conformers at cryogenic temperatures in a N2 matrix, and subsequent narrow-band near-infrared (NIR) laser excitation to give 1cc. Carbene 1cc converts quickly to 1ct via quantum-mechanical tunneling with an effective half-life of 22 min at 3 K. The potential energy surface features around 1 were pinpointed by convergent focal point analysis targeting the AE-CCSDT(Q)/CBS level of electronic structure theory. Computations of the tunneling kinetics confirm the time scale of the 1cc → 1ct rotamerization and suggest that direct 1cc → H2 + CO2 decomposition may also be a minor pathway. The intriguing latter possibility cannot be confirmed spectroscopically, but hints of it may be present in the measured kinetic profiles.

Photochemistry of HNSO2 in cryogenic matrices: spectroscopic identification of the intermediates and mechanism.

Small molecules solely consisting of H, N, O, and S are highly relevant intermediates in atmospheric chemistry and biology. Even though several isomers of [HNO2S] have been computationally predicted, only the IR spectra for the two lowest-energy isomers HNSO2 and syn-syn HONSO have been previously reported. Herein, the photochemistry (193 nm laser) of HNSO2 in N2-, Ne-, and Ar-matrices (≤15 K) has been studied. Aside from syn-syn HONSO, several new isomers including anti-syn HONSO, gauche-syn HOSNO, syn HOS(O)N, anti HOS(O)N, syn HS(O)NO, anti HN(O)SO, gauche-syn HSONO, and an elusive caged-radical pair HOS˙˙NO have been identified. Additionally, the formation of fragments HONO, HO˙, ˙NO, and ˙NO2 has also been observed. The characterization of these species with matrix-isolation IR and UV/Vis spectroscopy is supported by 15N-labeling and quantum chemical computations at the B3LYP/6-311++G(3df,3pd) level. Furthermore, the photo-induced isomerization reactions, including the conformational conversion of syn-syn HONSO → anti-syn HONSO and reversible isomerization of HOSNO ↔ anti-syn HONSO, syn-syn HONSO ↔ HN(O)SO, HSONO ↔ HS(O)NO, and HOS˙˙NO ↔ HOSNO have also been observed, and the underlying mechanism is discussed.

Capture and Reactivity of an Elusive Carbon-Sulfur Centered Biradical.

The initial oxidation product of dimethyl sulfide in the marine boundary layer, the methyl thiomethyl radical, has remained elusive. A structurally analogous biradical with one radical center in the α-position to a sulfur atom could now be obtained by UV irradiation of p-nitrobenzaldehyde dithiane isolated in solid dinitrogen (N2) or Ar at cryogenic temperatures. A spin-forbidden reaction with triplet dioxygen (3O2) does not occur. The dithiane of o-nitrobenzaldehyde rather undergoes a series of rearrangements under the same conditions, resulting in overall photodeprotection.

Gas-phase sugar formation using hydroxymethylene as the reactive formaldehyde isomer.

Carbohydrates (CH2O)n are the formal adducts of carbon (atoms) to water with a repeating unit that structurally resembles H-C̈-OH (hydroxymethylene). Although hydroxymethylene has been suggested as a building block for sugar formation, it is a reactive species that had escaped detection until recently. Here we demonstrate that formaldehyde reacts with its isomer hydroxymethylene to give glycolaldehyde in a nearly barrierless reaction. This carbonyl-ene-type transformation operates in the absence of base and solvent at cryogenic temperatures similar to those found in extraterrestrial environments or interstellar clouds. Hydroxymethylene acts as a building block for an iterative sugar synthesis, as we demonstrate through the formation of the triose glyceraldehyde. The thermodynamically preferred ketose dihydroxyacetone does not form, and the formation of further branched sugars in the iterative synthesis presented here is unlikely. The results therefore provide a link between the well-known formose (Butlerow) reaction and sugar formation under non-aqueous conditions.

Intricate Conformational Tunneling in Carbonic Acid Monomethyl Ester.

Disentangling internal and external effects is a key requirement for understanding conformational tunneling processes. Here we report the s- trans/ s- cis tunneling rotamerization of carbonic acid monomethyl ester (1) under matrix isolation conditions and make comparisons to its parent carbonic acid (3). The observed tunneling rate of 1 is temperature-independent in the 3-20 K range and accelerates when using argon instead of neon as the matrix material. The methyl group increases the effective half life (τeff) of the energetically disfavored s- trans-conformer from 3-5 h for 3 to 11-13 h for 1. Methyl group deuteration slows the rotamerization further (τeff ≈ 35 h). CCSD(T)/cc-pVQZ//MP2/aug-cc-pVTZ computations of the tunneling probability suggest that the rate should be almost unaffected by methyl substitution or its deuteration. Thus the observed relative rates are puzzling, and they disagree with previous explanations involving fast vibrational relaxation after the tunneling event facilitated by the alkyl rotor.