芳醛是合成C-C鍵的重要中間體。傳統(tǒng)合成方法（如羧酸/酯還原）存在諸多局限性，比如官能團(tuán)兼容性差、需低溫反應(yīng)、可能需多步預(yù)活化等。另外芳基鹵化物的直接甲酰化是單步替代方案，但傳統(tǒng)鹵素-金屬交換法需化學(xué)計(jì)量金屬試劑（如烷基鋰），強(qiáng)堿性條件限制官能團(tuán)耐受性。現(xiàn)有鈀催化還原羰基化（需高壓CO氣體）應(yīng)用受限，且無CO氣體的還原羰基化研究較少?！尽俊尽?/p>

小編今天推薦一個(gè)十幾年前報(bào)道的一個(gè)方法， 插羰制備芳醛，不用CO, 不用氫氣? 操作方便！

2013年， Tsuyoshi Ueda等人曾 報(bào)道了一種新型鈀催化還原羰基化方法，使用N-甲?；蔷?/strong>作為固體狀CO替代物，三乙基硅烷作為氫源，在無CO氣體條件下將芳基溴化物轉(zhuǎn)化為芳醛。該反應(yīng)僅需1.5當(dāng)量CO源和中等溫度條件，對(duì)多種官能團(tuán)（醚、酯、醛、氰基等）及雜芳環(huán)溴化物具有良好兼容性。機(jī)理研究表明，糖精的低親核性可抑制副反應(yīng)，?；蔷顷P(guān)鍵中間體。【

Angew. Chem. Int. Ed.

Na2CO3將N-甲?；蔷?strong>2d）轉(zhuǎn)化為糖精鈉和CO。隨后，糖精鈉與由1b的氧化加成和CO插入形成的?；Z物種C結(jié)合，從而生成D。鈀介導(dǎo)的可逆還原消除/氧化加成發(fā)生在6與D之間，隨后D與Et3SiH反應(yīng)生成3b和活性鈀物種A（路徑2）。然而，原假設(shè)中提到的替代機(jī)制（路徑1）仍不能排除。在這種路徑下，C無需糖精鈉參與可直接被Et3SiH還原生成3b。

實(shí)驗(yàn)操作

A typical experimental procedure for reductive carbonylation of 1bwith N-formylsaccharin. Pd(OAc)2 (10.1 mg, 0.045 mmol, 3.0 mol%), dppb (28.8 mg,0.068 mmol, 4.5 mol%), 2d (475 mg, 2.25 mmol, 1.5 equiv), and Na2CO3 (238 mg, 2.25 mmol, 1.5 equiv) were added to a 30 mL test tube, which was then evacuated and backfilled three times with N2. A degassed solution of 1b (158 mL, 1.50 mmol) and Et3SiH (311 mL, 1.95 mmol, 1.3 equiv) in DMF (6 mL) was added to the test tube under N2. The tube was immediately sealed by a plastic screw cap and the mixture was stirred for 10 min at RT (this stirring is critical for the selectivity of the reaction). The mixture was subsequently warmed to 75oC and stirred for a further 16 h. The reaction mixture was cooled to RT, then diluted with Et2O (15 mL), and washed with H2O (15 mL). The aqueous layer was extracted two times with Et2O (15 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated. The obtained residue was purified by flash column chromatography on silica gel (3–5% Et2O in npentane) to provide 3b as a colorless oil (132 mg,83%).

本文開發(fā)了一種無CO氣體的鈀催化芳基溴化物還原羰基化新方法，使用N-甲酰基糖精（2d） 作為高效CO源。該反應(yīng)僅需1.5當(dāng)量CO源和中等溫度條件，適用于多種芳基溴化物（含敏感官能團(tuán)及雜芳環(huán)）。相較于現(xiàn)有CO替代物，2d具有廉價(jià)、易得、穩(wěn)定、高活性等優(yōu)勢(shì)。

參考資料：Palladium-Catalyzed Reductive Carbonylation of Aryl Halides with N-Formylsaccharin as a CO Source；Tsuyoshi Ueda, Hideyuki Konishi, and Kei Manabe；

Angew. Chem. Int. Ed.