(1S)‐, 2,2′, 3,3′‐Tetrahydro‐1,1′‐spirobi [1H‐indene]‐7,7′‐diol

[223259-63-0] [223259-62-9] [223137-87-9] C17H16O2 (MW 252.31) InChI = 1S/C17H16O2/c18-13-5-1-3-11-7-9-17(15(11)13)10-8-12-4-2-6-14(19)16(12)17/h1-6,18-19H,7-10H2 InChIKey = YBRDFCQKQVTQKX-UHFFFAOYSA-N (chiral ligand and auxiliary) Alternate Name: SPINOL; 1,1′-Spirobiindane-7,7′-diol. Physical Data: mp 115–116 °C (racemic); mp 155–156 °C, = 33.7° (c = 1.0, CHCl3) (enantiomerically pure). Solubility: CH2Cl2, toluene, THF. Form Supplied in: crystalline solid; racemic compound is commercially available. (1) Reaction conditions: (a) Me2CO (0.5 equiv), NaOH (50% in EtOH–H2O), rt, 2 h, 62%; (b) Raney Ni, H2 (1 atm), Me2CO, rt, 1 day; (c) Br2 (2.5 equiv), pyridine (3.5 equiv), CH2Cl2, −10 °C to rt, 4 h; (d) polyphosphoric acid, 105 °C, 5.5 h, 57% for 3 steps; (e) n-BuLi (4 equiv), THF, −78 °C, 1 h, then EtOH, 93%; (f) BBr3 (2.3 equiv), CH2Cl2, −78 °C to rt, overnight, 85%. Preparative Methods: Synthesis of SPINOL. Preparation of racemic 1,1′-spirobiindane-7,7′-diol (SPINOL) was first reported by Birman.1 The synthesis began with the twofold aldol condensation of m-anisaldehyde 1 with acetone to give bis(m-anisylidene) acetone 2. Raney nickel-catalyzed hydrogenation of 2 provided 1,5-bis(3-methoxyphenyl)pentan-3-one 3. Electrophilic bromination of aryl rings was implemented to enforce the site selectivity during the key intramolecular Friedel–Crafts alkylation, which afforded the desired spirocyclic core of SPINOL 5. The protective bromide groups were subsequently removed via metalation/protonolysis to give 6, which upon BBr3-assisted cleavage of methyl ethers provided racemic SPINOL 7 (eq 1).1 Optical Resolution. The resolution of racemic SPINOL may be achieved by derivatization with l-menthyl chloroformate followed by separation of the resulting diastereomeric carbonates by flash column chromatography (eq 2).1 Alternatively, the resolution can be accomplished by cocrystallization of SPINOL with N-benzylcinchonidinium chloride.2 (2) Reaction conditions: (a) l-menthyl chloroformate (2.4 equiv), NEt3 (3.7 equiv), DMAP (10 mol %), CH2Cl2, rt, 9 h; flash chromatography (silica gel, 3 % Et2O in hexanes): 8a (95%), 8b (85%); (b) N2H4·H2O, THF, reflux, 1.5 h; from 8a: (R)-(+)−7 (86%), = +32.5° (c = 1.0, CHCl3); from 8b: (S)-(−)-7 (91%), = −32.7° (c = 1.0, CHCl3). 4,4′-Disubstituted SPINOLs. Synthesis of substituted SPINOL derivatives commenced with dibromide 5, which was used as an intermediate in the synthesis of racemic SPINOL described above (eq 1). Thus, deprotection of methyl groups produced a 4,4′-dibromo-SPINOL analog 9. Next, bis-dimenthyl carbonate derivatives 10 and 11 were prepared using a modified Birman procedure (eq 3).3, 4 Optical resolution of products was achieved by recrystallization of the diastereomeric mixture of 10 and 11 in n-hexane, which provided pure (S)-(+)-10 in 89% yield. The mother liquor was evaporated to dryness and subjected to column chromatography, upon which (R)-(−)-11 was obtained in 89% yield. Compound (S)-(+)-10 was then treated with n-BuLi and quenched with appropriate electrophiles (H+, I+, Me+) to install the respective substituents at the 4- and 4′-positions. Finally, the chiral carbonate moieties were cleaved by heating the products to reflux in ethanolic KOH, affording 4,4′-disubstituted SPINOL derivatives 12 (eq 3).3 (3)