案例一（反应条件解决）
巯基乙酸甲酯和丙烯酸甲酯经迈克尔加成得到化合物4，
化合物4采用常规条件，钠氢、烷基醇金属和金属HMDS，选择性不好，区域选择性差（杂质7）
采用四氯化钛和有机碱，操作角度有缺陷，主要是杂质多，二氢杂质和氯代杂质
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实验操作
Dichloromethane (51.0 L) followed by TiCl4 (10.84 kg, 57.15 mol) were charged under nitrogen into a jacketed reactor equipped with temperature probe, mechanical stirrer and dropping funnel. The solution was cooled to -10 °C and isopropanol (3.36 kg, 55.9 mol) was charged.
The mixture was stirred for 30 min and dimethyl 3-thiaadipate 4 (13.63 kg of a 70.0% solution in dichloromethane, 49.6 mol) was charged over 1 hour keeping the internal temperature at or below -10 °C. The resulting mixture was stirred for 30 min and triethylamine (17.42 kg, 172.2 mol) was charged over 1.5 h.
The resulting mixture was stirred at or below -10 °C for 1.5 and 3N HCl (48.1 kg, 144.3 mol) was slowly charged starting at -10 ºC and keeping the internal temperature below 10 °C. The batch was then stirred vigorously at 30 °C for a minimum of 1 hour. The mixture was allowed to settle, the organic portion was collected and the aqueous layer was extracted with dichloromethane twice (24 L per extraction). The combined organic layer was washed with water twice (24 L per wash) and concentrated under reduced pressure by distillation to give 7.45 kg (95.8 % weight by assay; 44.6 mol) of 5 in 89.8% yield.- 化合物3制备化合物1，先经化合物5，没有选择常用的试剂，氯代（溴代）乙酸乙酯，而是采用weinreb类型的酰胺，根本目的提高选择性。
DOI: 10.1021/acs.oprd.6b00104 (案例一）https://doi.org/10.1021/acs.oprd.3c00485 （案例二）Org. Process Res. Dev. 2024, 28, 609−618
