Convenient Formal Synthesis of (+)-Grandisol through Lewis Acid Promoted Enantioselective Pinacolic Rearrangement

Abstract

The titanium-mediated cyclopropanation of an easily prepared chiral a-siloxylactone leads efficiently to an enantiomerically pure cyclopropanol derivative. The trimethylsilyl trifluoro­methane sulfonate induced pinacol rearrangement allows high level of chirality transfer into a cyclobutanone, which is a useful intermediate in the total synthesis of (+)-grandisol.

antifugal agents - aldol reactions - rearrangements - ring expansion - ketones

References and Notes

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7

Reduction Procedure: To a solution of [(4S)-4-methyl-5-oxo-2-(tribromomethyl)-1,3-dioxolan-4-yl]acetic acid (4; 2.64 g, 6.45 mmol) in anhyd THF (15 mL) was added dropwise at -10 ˚C under argon a solution of borane methyl sulfide complex (1.75 mL, 3.48 mmol, 2 M in THF). After stirring for an additional hour at -10 ˚C, the reaction mixture was allowed to warm overnight to r.t. The mixture was quenched with MeOH (1 mL) and concentrated under reduced pressure and the resulting oil was diluted in Et₂O (50 mL). The ethereal phase was washed with brine (5 mL) and then dried over Na₂SO₄. After evaporation of the solvent, the residue was purified by flash chromatography to afford pure (3S)-dihydro-3-hydroxy-3-methyl-2(3H)-furanone (5; 0.65 g, 83%); [α]_D ^²0 -32.2 (c 0.1, CHCl₃).

8 Ohba M. Izuta R. Shimizu E. Chem. Pharm. Bull.  2006,  54:  63 

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11

Crystallographic data for (-)-9: C₁₃H₂₈O₃Si, M = 260.44, monoclinic, space group C2, a = 12.359(5) Å, b = 7.468(5) Å, c = 17.642(5) Å, β = 101.69˚, Z = 2, V = 1594.54 Å^³. Full crystallographic data have been deposited with the Cambridge Crystallographic Data Centre CCDC as supplementary publication number CCDC 697709. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge, CB2 IEZ, UK, fax:
[phone], e-mail: [e-mail]; www.ccdc.cam.ac.uk/data_request/cif.

12 Yu S.-H. Park J.-J. Chung S.-K. Tetrahedron: Asymmetry  2006,  17:  3030 

13

Selected data:
1-[(1 S )-1-( tert -Butyldimethylsilyloxy)-3-hydroxy-1-methylpropyl]cyclopropanol (9): colorless needles; mp
65 ˚C; [α]_D ^²0 -12 (c 0.1, CHCl₃). IR (KBr): 3289, 2957, 1464, 1254 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 3.94-4.03 (m, 1 H), 3.64-3.78 (m, 1 H), 2.02-2.07 (m, 1 H), 1.70-1.87 (m, 1 H), 1.31 (s, 3 H), 0.82-0.97 (m, 2 H), 0.84 (s, 9 H), 0.59-0.64 (m, 2 H), 0.11 (s, 3 H), 0.07 (s, 3 H). ^¹³C NMR (62.9 MHz, CDCl₃): δ = 75.3, 60.1, 58.3, 43.0, 41.9, 25.2, 11.4, 8.2, 2.6, 2.3. HRMS (ES, +): m/z calcd for C₁₃H₂₈O₃SiNa: 283.17054; found: 283.17058.
1-[(1 S )-3-(Benzyloxy)-1-( tert -butyldimethylsilyloxy)-1-methylpropyl]cyclopropanol (12): colorless oil; [α]_D ^²0 -34 (c 0.05, CHCl₃). IR (neat): 3501, 2929, 1454, 1256 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.29-7.37 (m, 5 H), 4.54 (Abq, J = 3.3 Hz, 2 H), 3.96-4.03 (m, 1 H), 3.71-3.78 (m,
1 H), 3.69 (s, 1 H), 1.99-2.15 (m, 1 H), 1.89-1.97 (m, 1 H), 1.27 (s, 3 H), 0.76-0.93 (m, 2 H), 0.87 (s, 9 H), 0.59-0.63 (m, 2 H), 0.10 (s, 3 H), 0.06 (s, 3 H). ^¹³C NMR (62.9 MHz, CDCl₃): δ = 129.2, 128.4, 128.2, 126.9, 78.2, 58.6, 40.0, 37.3, 29.2, 26.2, 25.6, 9.4, 7.5, 2.8, 2.3. HRMS (ES, +): m/z calcd for C₁₉H₃₄O₃SiNa: 373.21749; found: 373.21712. (2 R )-2-(2-Benzyloxyethyl)-2-methylcyclobutanone (2): colorless oil; [α]_D ^²4 +42 (c 0.1, CHCl₃). IR (neat): 1765
cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.30 (m, 5 H), 4.43 (Abq, J = 11.7 Hz, 2 H), 3.56 (t, J = 6.3 Hz, 2 H), 2.98 (t, J = 6.3 Hz, 2 H), 1.93-2.01 (m, 2 H), 1.86 (s, 3 H), 1.64-1.79 (m, 2 H). ^¹³C NMR (62.9 MHz, CDCl₃): δ = 214.8, 138.1, 128.2, 127.4, 127.3, 72.8, 66.7, 62.2, 42.3, 35.3, 23.9, 21.3. MS (EI): m/z (%) = 218 (1) [M⁺], 127 (12), 97 (11), 91 (100), 41 (38).