Bithiophene with Winding Vine-shaped Molecular Asymmetry. Preparation, Structural Characterization, and Enantioselective Synthesis

Abstract

Preparation of 2,2¤-bithiophene derivatives bearing ω-alkenyl groups at the 3,3¤-positions and ring-closing metathesis reactions of the obtained compound were performed. The reaction of bithiophene bearing 3-butenyl substituents 1 with 5 mol % Grubbs 1st generation catalyst underwent ring-closing metathesis (RCM) to afford the cyclized product 7 showing winding vine-shaped molecular asymmetry in up to 88% yield. Enantioselective RCM was also achieved by the use of chiral Schrock Hoveyda molybdenum-alkylidene catalyst in up to 87% ee.

Synthesis and Racemization Studies of Winding Vine‐Shaped Biphenyl Derivatives

“…The angle was similar to that of the bithiophene derivative 2 (76.9°). [6] The CÀ C bond of the ethylenediamine moiety (C7-C8) was revealed to be intersected with the CÀ C bond between two benzene rings of biphenyl (C15-C16) with the torsion angle of 61.9°. By contrast, the aniline derivative 8 a' was found to show almost parallel conformation of the CÀ C bond of the two phenyl rings of biphenyl (C13-C14) and the CÀ C bond of the diamine moiety (C21-C22) with the torsion angle of 7.8°, as shown in Figure 2b.…”

“…[5] It was also revealed that the obtained product exhibited molecular asymmetry, in which axial, helical, and planar chiralities were involved in the molecule and their inversion of the chirality took place in a synchronized manner. Separation of the enantiomer with HPLC on chiral stationary phase, [3,6] resolution with the preparative column, [3] and enantioselective metathesis [7,8] have been successful to afford the enantiomerically pure/enriched compounds. It was also shown to undergo an additional protocol to afford winding vine-shaped molecules employing annulative nucleophilic substitution with nosyl (2-nitrobenzenesulfonyl) diamines to give vine-shaped biaryl 2.…”

“…It was also shown to be calculated that the energy barrier of the related derivative 1 bearing CÀ C double bond was slightly higher but 1 still slowly racemized experimentally even at room temperature. [6] Although the related non-heteroaromatic analogs 3 composed of the benzene ring was suggested to racemize with a higher energy barrier by DFT calculation, [10] the actual synthesis of such biphenyl 3 has not been successful to date. Accordingly, we envisaged to synthesize the vine-shaped biphenyl derivatives and to study their racemization behaviors.…”

“…We have preliminarily studied the DFT calculation on the racemization behavior [10] of thus cyclized heterobiaryls 2 and found that the isomerization barrier of 2 was much lower because of the ease of the free rotation of the carbon‐carbon single bond. It was also shown to be calculated that the energy barrier of the related derivative 1 bearing C−C double bond was slightly higher but 1 still slowly racemized experimentally even at room temperature [6] . Although the related non‐heteroaromatic analogs 3 composed of the benzene ring was suggested to racemize with a higher energy barrier by DFT calculation, [10] the actual synthesis of such biphenyl 3 has not been successful to date.…”

Chirality recognition of winding vine-shaped heterobiaryls with molecular asymmetry. Kinetic and dynamic kinetic resolution by Shi’s asymmetric epoxidation

“…Unsymmetrical heterbiaryls (±)- 4b , (±)- 4c , and (±)- 4e were prepared by the procedures in our previous report 22 . Bithiophene (±)- 4d was prepared by the procedure described in our previous report 21 . Racemic epoxides 3 and 5d were prepared by epoxidation of (±)- 1 and (±)- 4d with m -chloroperbenzoic acid or oxone/acetone in a manner described previously 23 .…”