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. 2015 Mar 6;54(17):5232–5235. doi: 10.1002/anie.201500401

Scheme 3.

Scheme 3

Synthesis of tetraketide 2 b and pentaketide 3 b as model substrates for Ela-TE. Reagents and conditions: A) a) i. nBu2BOTf, TEA, CH2Cl2, −78 °C, ii. EtCHO, −78 °C to 0 °C, 3 h, 65–68 % (ds>95:5). b) LiBH4, THF, MeOH, 45 mins, 0 °C. c) 1-(dimethoxymethyl)-4-methoxybenzene, CSA, CH2Cl2, RT, 93 % (for two steps). d) DIBAL, CH2Cl2, 45 mins, 0 °C, 99 %. e) TsCl, DMAP, TEA, CH2Cl2, RT, 4 h, 90 %. f) LiBH4, THF, 0 °C to RT, 24 h, 85 %. g) OsO4, NMO, buffer pH 7, THF/acetone, 5 h, RT. h) NaIO4, buffer pH 7, THF, 12 h, (86 % for two steps). i) i. LiHMDS, THF, −78 °C to −25 °C, 30 mins, ii. (E)-ethyl 4-(diethoxyphosphoryl)but-2-enoate, THF, −78 °C to −25 °C, 84 %. j) KOH, EtOH/H2O, 12 h, RT, 99 %. k) N-(2-mercaptoethyl)acetamide, DCC, HOBt, DMF, 0 °C to RT, 12 h, 67 %. l) DDQ, buffer pH 7, DCM, 0 °C, 80 %. B) a) i. nBu2BOTf, DIPEA, CH2Cl2, −10 °C, ii. −78 °C, (S)-3-((4-methoxybenzyl)oxy)-2-methylpropanal, 70 %(ds>95:5). b) N,O-dimethylhydroxylamine hydrochloride, Me3Al, THF, 6 h, 0 °C to RT, 72 %. c) TBSOTf, CH2Cl2, 2,6-lutidine, 1 h, 0 °C to RT, 79 %. d) EtMgBr, THF, 5 h, 0 °C, 78 %. e) HF⋅Py, THF, 0 °C to RT, 12 h, 95 %. f) Me4NBH(OAc)3, MeCN, AcOH, 12 h, −30 °C to −20 °C, 88 %. g) TBSOTf, 2,6-lutidine, CH2Cl2, 1 h, 0 °C to RT, 87 %. h) DDQ, buffer pH 7, CH2Cl2, 0 °C, 82 %. i) (COCl)2, DMSO, TEA, CH2Cl2, −78 °C, 2 h, 86 %. j) i. LiHMDS, THF, −78 °C to −25 °C, 30 mins, ii. (E)-ethyl 4-(diethoxyphosphoryl)but-2-enoate, THF, −78 °C to −25 °C, 2 h, 94 %. k) KOH, EtOH/H2O, 12 h, RT, 99 %. l) N-(2-mercaptoethyl)acetamide, DCC, HOBt, DMF, 0 °C to RT, 12 h. m) HF⋅Py, THF, 0 °C to RT, 12 h, 51 % (two steps). ds=diastereoselectivity. TEA=triethylamine, CSA=10-camphorsulfonic acid, DIBAL=diisobutylaluminum hydride, Ts=4-toluenesulfonyl, DMAP=4-dimethylaminopyridine, NMO=N-methylmorpholine-N-oxide, DCC=1,3-dicyclohexylcarbodiimide, HOBt=1-hydroxybenzotriazole, DMF=N,N-dimethylformamide, DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone, DIPEA=N,N-diisopropylethylamine, TBSOTf=tert-butyldimethylsilyl trifluoromethanesulfonate, LiHMDS=lithium hexamethyldisilazane.