Synthesis, Resolution, and Determination of Absolute Configuration of a Vaulted 2,2‘-Binaphthol and a Vaulted 3,3‘-Biphenanthrol (VAPOL)

Abstract

Two methods for the synthesis of vaulted biaryls were developed involving the reactions of carbene complexes with alkynes and the [2 + 2] cycloaddition of ketenes. The final step in the synthesis of 3,3‘-diphenyl-[2,2‘-binaphthalene]-1,1‘-diol (39) and 2,2‘-diphenyl-[3,3‘-biphenanthrene]-4,4‘-diol (47) (VAPOL) was phenol coupling of the 3-phenyl-1-naphthol (14) and the 2-phenyl-4-phenanthrol (28), respectively. The naphthol 14 could be prepared from the thermolysis of phenylacetyl chloride in the presence of phenylacetylene or from the benzannulation of the pentacarbonyl(phenylmethoxymethylene)chromium(0) (15) with phenylacetylene which upon an acetylative workup gives O-acetyl-4-methoxy-2-phenyl-1-naphthol (16). The reductive cleavage of the acetoxy group in 16 was unexpectedly affected by aluminum chloride and ethanethiol which were used to cleave the methyl ether. In a similar manner, the phenanthrol 28 could either be prepared from the 1-naphthylacetyl chloride (30) or pentacarbonyl(1-naphthylmethoxymethylene)chromium(0) (21). A new procedure for the preparation of carbene complexes was developed utilizing dimethyl sulfate as methylating agent. Unlike the benzannulation of the phenyl complex 15, the benzannulation of the naphthylcarbene complex 21 with phenylacetylene gave a side product which resulted from the incorporation of 2 equiv of the alkyne. This side product could be minimized by the proper control of the concentration of the alkyne. The phenol coupling of the 3-phenyl-1-naphthol with ferric chloride gave 2,2‘-diphenyl-[2,2‘-binaphthalene]-4,4‘-diol (38) and with air as oxidant gave the of 3,3‘-diphenyl-[2,2‘-binaphthalene]-1,1‘-diol (39). Oxidative coupling of the 2-phenyl-4-phenanthrol (28) with air gave 2,2‘-diphenyl-[3,3‘-biphenanthrene]-4,4‘-diol (47) (VAPOL), but the same coupling with 2-tert-butyl-4-phenanthrol (34) failed. The 2,2‘-binaphthol 39 was resolved via its cyclic diester with phosphoric acid by salt formation with (−)-brucine, and the 3,3‘-biphenanthrol 47 was resolved via its cyclic deiester with phosphoric acid (49) by salt formation with (−)-cinchonidine. The configuration of (−)-39 was shown to be S from an X-ray analysis of the brucine salt, and the configuration of (+)-47 was shown to be S from an X-ray analysis the amide (S,S)-54 derived from 49 and (S)-α-methylbenzylamine.

Determination of the absolute stereochemistry of chiral biphenanthryls in solution phase using chiroptical spectroscopic methods: 2,2′‐Diphenyl‐[3,3′‐biphenanthrene]‐4,4′‐diol

“…Thus, all three chiroptical spectroscopic methods independently suggest that the absolute configuration of VAPOL is (2)-(aR), which is in agreement with that derived from X-ray diffraction data of its phosphoric amide derivative. 3 It is to be noted that while reliable VCD predictions for most molecules can normally be obtained at the B3LYP/6-31G* level of theory, ECD and ORD predictions require, quite often, higher levels of theory. Since all three predictions for VAPOL provided consistent configurational assignment, we have not attempted to perform ECD and ORD calculations at higher levels of theory.…”

“…In chemical synthesis, compounds containing phenanthryl groups are considered to have an important role. In particular, 2,2 0 -diphenyl-[3,3 0 -biphenanthrene]-4,4 0 -diol, also known as VAPOL, and its derivatives have been identified [3][4][5] as highly effective enantioselective catalysts and ligands. Their utility spans a range of asymmetric reactions such as the Diels-Alder, 6,7 imino-aldol, 8 and aziridination [9][10][11] reactions.…”

Preparation of New Binaphthol Derived Chiral Stationary Phases

“…These simple reactions have been reported in literature previously. 4,5,[8][9][10][11][12] First, the mono-substituted compound 1 was a major product at low temperatures, but a disubstituted product also appeared. Because the yield of the esterification was bigger than the amidation (the first step of synthesis of CSP 3), the di-substituted one could be cleanly and easily removed by classical extraction with high pH (~13) of the aqueous solution.…”

“…The silica gel was filtered and washed extensively with toluene, ethyl acetate, methanol, acetone, diethyl ether and hexane successively. Then the modified silica gel was slurried in methanol and packed into a 4.6 mm ID, 250 mm length stainless steel HPLC column using a conventional method 8,9 with an Alltech HPLC Slurry Packer.…”

Study of stereomeric peptoid chiral stationary phases containing different chiral side chains

“…As valuable biaryl ligand in asymmetric synthesis [28], 3,3 -diphenyl-2,2 -bi-1-naphthalol (VANOL, TR 7) has attracted a lot of attention in synthesis and chiral resolution [29][30][31]. With 50% chloroform in n-hexane as eluent, excellent resolution of VANOL can also be achieved (˛ = 19.96, Rs = 13.22, Fig.…”