CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

(i) PhCHO, triethyl orthoformate, MeC 6 H 4 -p-SO 3 H, Δ; (ii) LAH, AlCl 3 , Et 2 O-CH 2 Cl 2 , Δ ;
(iii) MeC 6 H 4 -p-SO 3 H, acetone, 23 °C; (iv) H 2 , Pd(OH) 2 , 25 °C; (v) Ph 3 P,
EtO 2 CN=NCO 2 Et, benzene, Δ; (vi) PhMgBr, CuCN, THF, -40°C-0°C; (vii)
(PhO 2 ) 2 P(O)N 3 , Ph 3 P, EtO 2 CN=NCO 2 Et, THF, -10°C-23°C; (viii) Aqueous 40% AcOH,
90 °C; (ix) MeCO 2 C(Me) 2 COCl, CHCl 3 , 23°C; (x) NaOMe, THF, 23°C.
Scheme IV.4.1
In another approach (Scheme IV.4.2), Bennet et al. 170a
synthesized the title
compound VI starting from phenylacetaldehyde 157, which was converted to the (E)-α,βunsaturated
ester 158. Reduction of 158 followed by Katsuki-Sharpless asymmetric
epoxidation yielded 159 with >95% e.e. Regioselective, nucleophilic azide ring opening of
the epoxide 159 gave diol 160, which after converting to primary tosylate and subsequent
treatment with sodium hydride in DMF yielded VI in 70% overall yield.
CHO i CO2 Et ii, iii O OH iv
OH
N OH
Ph
3
Ph
157 158
Ph
159 Ph 160
v, vi
VI
(i) t-BuOK, (EtO) 2 P(O)CH 2 CO 2 Et, THF, -78 °C; (ii) (Me 2 CHCH 2 ) 2 AlH, CH 2 Cl 2 , -78°C-25
°C; (iii) Ti(OPr i ) 4 , t-BuOOH, D -(-)-DET, CH 2 Cl 2 , -23°C; (iv) [Ti(OPr i ) 2 (N 3 ) 2 ], benzene,
75°C; (v) p-TsCl, cat. DMAP, pyridine, 0 °C; (vi) NaH, DMF, 0 °C.
Scheme IV.4.2
170