A Route to Carbasugar Analogues - Jonathan Clayden - The ...

Experimental for chapter 3.2
Synthesis of ((1S,4S,5S)-4-(hydroxymethyl)-5-isopropyl-4-methylcyclohex-2-enol)
bis para-bromobenzoate (115)
O
HO
Cl
Br Br
DMAP
Et
OH
3 N, CH 2 Cl 2
8
9
O
O
7
1 2
3
6
4
5
O
O
Br
4-bromobenzoyl chloride (120 mg, 0.55 mmol) was added to a solution of diol 225 (20
mg, 0.1 mmol), DMAP (2 mg, 0.02 mmol), triethylamine (1 cm 3 ) in CH 2 Cl 2 (5 cm 3 )
under a nitrogen atmosphere. After 12 hr sodium hydroxide (2.5 cm 3 , 3M aq.) was
added to the reaction and stirred for 1 hr before being partitioned in EtOAc (1 cm 3 ) and
the organic layer washed sequentially with HCl (3M aq.), sodium bicarbonate, and
brine. The organic layer was dried over anhydrous sodium sulphate and solvent
evaporated to give a clear yellow oil, which was purified by flash column
chromatography (99:1 petrol:EtOAc) to give benzoyl ester 115 (34 mg, 62%) as a
white oil.
R f : 0.46 (9:1, petrol:EtOAc); [α] 21 D : –15 (c = 1.0, CHCl 3 ); IR ν max (film)/cm⎯¹ 2960
(m), 1717 (C=O), 1590 (m), 1266, 1101 (m); ¹H-NMR (CDCl 3 , 500 MHz) δ 7.92 (d,
2H, J 8.5, H8 or H8'), 7.82 (d, 2H, J 8.5, H8 or H8'), 7.61-7.55 (m, 4H, H9, H9'), 5.78-
5.72 (m, 1H, H5), 5.66 (dd, 1H, J 10.0, 2.0, H6), 5.64-5.59 (m, 1H, H4), 4.34 (d, 1H, J
11.0, H7 a ), 4.26 (d, 1H, J 11.0, H7 b ), 2.19-2.07 (m, 2H, H3, CHMe2), 1.85-1.76 (m,
1H, H3), 1.58 (d, 1H, J 14.0, H2), 1.16 (s, 3H, Me), 1.04 (d, 3H, J 7.0, i-Pr), 0.90 (d,
3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 165.6 (C=O), 165.5 (C=O), 137.7 (C6
or C5), 131.8, 131.7, 131.1, 129.3, 129.1, 128.1, 128.1 (Ar), 127.4 (C6 or C5), 72.2
(C4), 68.6 (C7), 46.9, 39.5 (C2, C1), 25.7, 25.5 (C3, CHMe 2 ), 24.5 (CHMe a Me b ), 24.4
(Me), 18.0 (CHMe a Me b ); Chiral HPLC: DAICEL Chiralcel OD-H, 2.5% IPA in
hexane, 0.5 ml/min, 11.3 min (0.2%), 12.7 min (99.8%); racemic sample: 11.3 min
(49.6%), 12.9 min (50.4%).
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