Page 223 - 精细化工2020年第2期

第 2 期 唐裕才，等: 基于烯胺酮中间体“一锅两步”法合成 β-羰基砜衍生物 ·425·

图 1 可能的反应机理
Fig. 1 Possible reaction mechanism

首先，在 DMF-DMA 试剂作用下，苯乙酮转化 [4] Lythgoe B, Waterhouse I. A synthesis of disubstituted acetylenes[J].
.
为活泼的烯胺酮中间体。苯磺酰肼在 FeCl 3 6H 2 O/ Tetrahedron Letters, 1978, 19(29): 2625-2628.
[5] Bartlett P, Green F, Rose E. Synthesis of acetylenes from carboxylic
TBHP 共同作用下发生脱氮气反应生成磺酰基自由 acid derivatives via β-keto sulfones[J]. Journal of the American
基。随后，磺酰基自由基对烯胺酮结构中的碳碳双 Chemical Society, 1978, 100(15): 4852-4858.
[6] Ihara M, Suzuki S, Taniguchi T. Preparation of olefins and acetylenes
键（羰基的 α 位）发生自由基加成反应生成中间体
viareductive elimination with SmI 2-HMPA[J]. Tetrahedron, 1995,
1。中间体 1 进一步被氧化成碳正离子，邻近氮原子 51(36): 9873-9890.
上未成键的孤对电子有助于稳定生成的碳正离子， [7] Sengupta S, Sarma D, Mondal S. γ-Chiral β-ketosulfones in
asymmetric synthesis: a unified synthetic strategy for enantiopure
这也是磺酰基自由基易于加成在 α 位的原因。中间
γ-amino and γ-hydroxy vinyl sulfones[J]. Tetrahedron: Asymmetry,
体 1 芳环上羰基邻位 R 1 如果是卤素（如氯、溴）， 1998, 9(13): 2311-2316.
则容易发生脱卤反应而得不到目标产物 [16] 。最后水 [8] Marco J, Ferna´ndez I, Khiar N, et al. Michael additions of
α-sulfinyl: The unprecedented reaction of β-keto sulfones with highly
分子对碳正离子发生亲核加成以及脱去一分子 DMF，
stabilized michael acceptors[J]. The Journal of Organic Chemistry,
得到最终 β-羰基砜产物。 1995, 60(21): 6678-6679.
3 结论 [9] Gotor V, Rebolledo F, Liz R. Enantioselective bioreduction of β-keto
sulfones with the fungus curvularia lunata[J]. Tetrahedron: Asymmetry,
2001, 12(3): 513-515.
在 100 ℃下将苯乙酮及衍生物与 DMF-DMA [10] Vennstra G, Zwaneburg B. An improved synthesis of sulfones using
试剂反应转化为活泼的烯胺酮中间体，随后以 tetrabutyl-ammonium sulfinates[J]. Synthesis, 1975, 1975(8): 519-520.
FeCl 3 ·6H 2 O/TBHP 为催化氧化体系，甲苯为溶剂， [11] Lu Q, Zhang J, Zhao G, et al. Dioxygen-triggered oxidative radical
reaction: Direct aerobic difunctionalization of terminal alkynes
80 ℃下发生自由基磺酰化反应，制备了 18 种含不 toward β-keto sulfones[J]. Journal of the American Chemical Society,
同取代基团的 β-羰基砜衍生物，目标产物收率 2013, 135(31): 11481-11484.
[12] Wei W, Liu C, Yang D, et al. Copper-catalyzed direct oxysulfonylation
30%~64%。考察了不同氧化剂、催化剂、溶剂对第
of alkenes with dioxygen and sulfonylhydrazides leading to
二步磺酰化反应的影响，确定了最优的反应条件， β-ketosulfones[J]. Chemical Communications, 2013, 49(87): 10239-
通过不同的芳香酮和磺酰肼衍生物验证了底物的普 10241.
[13] Tang X, Huang L, Xu Y, et al. Copper-catalyzed coupling of oxime
适性。该合成方法具有操作简便、底物适用较广等
acetates with sodium sulfinates: An efficient synthesis of sulfone
优点，为 β-羰基砜类化合物的合成提供了理论依据。 derivatives[J]. Angewandte Chemie International Edition, 2014,
53(16): 4205-4208.
参考文献： [14] Li X, Shi X, Fang M, et al. Iron halide-mediated regio- and
stereoselective halosulfonylation of terminal alkynes with
[1] Ma M, Cheng Y, Xu Z, et al. Evaluation of polyamidoamine
(PAMAM) dendrimers as drug carriers of anti-bacterial drugs using sulfonylhydrazides: Synthesis of (E)-β-chloro and bromo vinylsulfones
sulfamethoxazole (SMZ) as a model drug[J]. European Journal of [J]. The Journal of Organic Chemistry, 2013, 78(18): 9499-9504. 3
Medicinal Chemistry, 2007, 42(1): 93-98. [15] Zhou P, Hu B, Li L, et al. Mn(OAc) 3-promoted oxidative C sp –P
2
2
[2] Fuchs P, Braish T. Multiply convergent syntheses via conjugate- bond formation through C sp –C sp and P–H bond cleavage: Access to
addition reactions to cycloalkenyl sulfones[J]. Chemical Reviews, β-ketophosphonates[J]. The Journal of Organic Chemistry, 2017,
1986, 86(5): 903-917. 82(24): 13268-13276.
[3] Liao C, Liu F, Guo Y, et al. Occurrence of eight bisphenol analogues [16] Hokamp T, Dewanji A, Lgbbesmeyer M, et al. Radical
in indoor dust from the united states and several asian countries: hydrodehalogenation of aryl bromides and chlorides with sodium
Implications for human exposure[J]. Environmental Science & hydride and 1, 4-dioxane[J]. Angewandte Chemie International
Technology, 2012, 46(16): 9138-9145. Edition, 2017, 56(43): 13275-13278.