Cyclohexene‐Embedded Dicyanomethylene Merocyanines – Consecutive Three‐Component Coupling‐Addition Synthesis and Chromophore Characteristics

Abstract A concise and efficient consecutive three‐component alkynylation‐addition synthesis of cyclohexene‐embedded dicyanomethylene merocyanines furnishes a small library of dyes in moderate to excellent yield. The dyes possess strong absorption coefficients of the longest wavelength absorption bands. According to the crystal structure, the small bond length alternations account for a highly delocalized electronic ground state. The electronic structure of the absorption bands is qualitatively rationalized by TDDFT calculations, which explain that intense HOMO‐LUMO transitions along the merocyanine axis lead to cyanine similar Stokes shifts.

The cooling was removed and stirring at room temp was continued for 2 h. The solvent was removed under reduced pressure and the crude product was purified by chromatography on

Optimization of the Consecutive Three-component Reaction
For the synthesis of the merocyanines 6, the standard conditions with the catalyst system PdCl2(PPh3)2/CuI and triethylamine as a base 2 were first chosen for the Sonogashira coupling using (TMS)acetylene (4a) and phenylacetylene (4b) as alkynes (Scheme S1). The Michael addition was performed under microwave irradiation at 100 °C for 1 h.
Scheme S1. Three-component reaction for the synthesis of merocyanines 6 under standard conditions. 2

Synthesis of Alkyne Intermediates A
Due to the moderate yields of 37 and 59 %, respectively, the three-component synthesis was optimized. In order to determine which partial reaction of the three-component reaction is the problem and thus responsible for the low yields, the intermediate alkynes A were first isolated.
The low yields of the Sonogashira reaction indicated that the subsequent Michael addition obviously proceeded nearly quantitatively. Therefore, the parameters for Sonogashira coupling in the three-component sequence were optimized. Indeed, DIPEA (diisopropylethylamine) turned out to be a favorable base for efficiently performing the Sonogashira alkynylation. S8

Optimization of the Alkynylation within the Sequence
In the model reaction for optimizing the alkynylation within the sequence triflate 3, (TMS)acetylene (4a), and pyrrolidine (5a) were reacted upon variation of the Pd catalyst and the employed base maintaining the standard reaction temperatures and reaction times (RT for 1 h for the alkynylation, MW (100 °C) for 1 h for the Michael addition with addition of methanol as a cosolvent) to give merocyanine 6a (Scheme S3, Table S1).
Scheme S3. Optimization of the catalyst and the base in Sonogashira coupling step of the three-component synthesis of merocyanine 6a.
In a first optimization approach of the three-component synthesis, a Pd 0 species, tetrakis(triphenylphosphane)palladium, was chosen instead of PdCl2(PPh3)2. However, this resulted in a collapse of the yield to 22% (Table S1, entry 2). It was observed that the inorganic base K2CO3 did not lead to any conversion (Table S1, entry 3), however, diisopropylethylamine (DIPEA) doubled the yield to 68% (Table S1, entry 4). Subsequently, S10 the optimization was checked by using the phenylacetylene instead of TMSA (Table S1, entry 5) and merocyanine 6b could was isolated in a yield of 95%. This represents a quantitative conversion to the desired reaction product.
a No conversion to compound 6a observed.

General procedure (GP) for the consecutive three-component synthesis of merocyanines 6 and 8
In a microwave vessel with magnetic stir bar were placed PdCl2(PPh3)2 (2 mol%, 14 mg), CuI (4 mol%, 7 mg), and triflate 3 (1.00 equiv.) in dry, degassed THF (1 mL) (for experimental details, see Table S1). After addition of alkyne 4 (1.00 equiv.) and DIPEA (1.00 equiv.) the reaction mixture was stirred under nitrogen at room temp for 1 h. Then, nucleophile 5 or 7 (1.00 equiv.) in methanol (1 mL) was added and the reaction mixture was heated in the microwave reactor at 100 °C for 1 h. After cooling to room temp the solvents were removed in vacuo and the crude product was purified by flash chromatography on silica gel to give merocyanines 6 or 8.

Determining the Barriers from the VT 1 H NMR Spectra of Merocyanine 6f
Assuming a reversible dynamic process with first-order kinetics the rate constant k of the Eyring equation 1 is defined as: G ≠ = Free activation enthalpy, NA = Avogadro number, h = Planck constant.
For two separated signals A and B, the absorption of the exchanging nuclei is slow. In the case of fast conversions, these signals coincide. At the point where the signals merge is the coalescence temperature Tc. At this temperature, the rate constant is approximated:  = absorption in Hz.