English

• 螺[1-苯并呋喃-3-酮-2, 2'-环戊烷]结构单元是许多具有优良生物活性的天然产物及生物活性化合物的核心结构^[1].例如:新近从树舌灵芝中分离得到的applanatumin A中便含有该结构骨架^[1a](Figure 1).基于此, 构筑此类母核结构就引起了许多课题组的研究兴趣^[2].而利用π-电子体系化合物参与的环合反应来构筑此类环状或多环化合物是常用及高效的策略^[3].近年来, 叔膦促进下的联烯酸酯与烯烃的环化反应作为高效构筑官能团化的碳环及杂环化合物的重要策略, 受到了化学家们的广泛关注^[4].陆熙炎课题组^[5]在1995年首先报道了三苯基膦催化下联烯酸酯与缺电子烯烃可以发生[3+2]环化反应, 并以高产率得到α-选择性和γ-选择性两种区域选择性成环的环戊烯衍生物.该反应后来被命名为陆氏[3+2]环化反应^[4].伴随着科研工作者对该反应的深入研究及对叔膦试剂的开发^[6], 陆氏[3+2]环化反应已经很好地实现了区域选择性与立体选择性的控制^{[2b, 7]}, 并在天然产物的全合成中得到了广泛的应用^[8].尽管, 利用陆氏[3+2]环化反应构筑螺[1-苯并呋喃-3-酮-2, 2'-环戊烯]结构单元, 已经实现了较好的区域选择性与优秀的对映选择性控制^[2b], 但是考虑到手性膦试剂的稳定性及合成难度, 加之我们对applanatumin A等活性天然产物的合成计划, 本文将报道在三苯基膦催化下, 以联烯丁酸酯及橙酮类化合物作为原料, 借助陆氏[3+2]环化策略来构筑螺[1-苯并呋喃-3-酮-2, 2'-环戊烷]的前体化合物螺[1-苯并呋喃-3-酮-2, 5'-环戊烯].

  图 1

  

  图 1.  代表性螺环化合物

  Figure 1.  Representative spiro compounds

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  1.   结果与讨论

  1.1   反应条件优化

  首先在三苯基膦催化下, 将橙酮类化合物1a作为模板底物, 开展其与联烯丁酸酯2a的环化反应中诸多反应参数的探索(Table 1).初次尝试陆氏[3+2]环化反应是在35 ℃下, 在氩气氛围中, 以PPh₃ (10 mol%)作为催化剂, 1a (1.0 equiv.)与2a (2.0 equiv.)在甲苯中反应.经过18 h反应, 以82%的产率得到螺环化产物.产物通过NMR谱分析发现, 其γ-选择性产物3a-γ与α-选择性产物3a-α比例为2.3/1, 且其相对立体化学与文献报道一致^[2b](表 1, Entry 1).初步的实验过程尽管得到了良好的结果, 然而反应过程中仍有原料1a剩余.为了进一步提高反应的转化率, 随即对物料比进行了筛查(表 1, Entries 2, 3).通过筛查发现, 当提高2a的用量至2.5 equiv.时, 该反应在13 h就可反应完全, 以96%的分离收率得到环化产物, 反应的区域选择性不变(表 1, Entry 2).而进一步提高联烯酸酯2a的用量, 反应的效果并无提高(表 1, Entry 3).为了探究反应催化剂对反应的影响, 随后对这一反应参数进行了研究(表 1, Entries 4~8).当使用PBu₃作为催化剂时, 反应能以82%的分离收率得到环化产物, 然而该反应的区域选择性却是以α-选择性产物为主(3a-γ/3a-α＝1/2.8).造成这一结果的原因, 可能是由于PBu₃比PPh₃更大的位阻影响.而PMe₃或PCy₃为催化剂时, 该环化反应只能以较低产率(分别为18%和21%)得到区域选择性几乎为1/1的产物, 且反应中有大量原料剩余(表 1, Entries 5, 6).当使用Et₃N或AsPh₃作为催化剂时, 该反应都无法顺利发生(表 1, Entries 7, 8).因而, 使用其它催化剂都无法得到比PPh₃作为催化剂时更为积极的结果.并且, 当降低或提高催化剂PPh₃的用量时, 该反应的产率都有明显下降, 区域选择性也略有下降(表 1, Entries 9, 10).继而, 又筛查了溶剂参数对反应的影响(表 1, Entries 11~14).从表中所列数据易知, 溶剂改变使得反应产率较之甲苯作溶剂时的结果有明显的降低, 甚至使反应无法发生.其中, 以乙腈作为溶剂时, 该反应可以得到较好的区域选择性(3a-γ/ 3a-α＝5.3/1), 但是反应中有大量原料剩余, 反应的产率只有12%(表 1, Entry 11).温度对该反应也影响明显(表 1, Entries 15~17).如表中数据所示, 无论降低或者升高反应的温度, 都未能得到比35 ℃时更好的反应结果, 对反应的区域选择性也只有轻微影响.最后, 将该反应置于敞开体系中反应时, 反应的产率下降也很显著(表 1, Entries 18, 19).即便在该反应进行过程中再补加10 mol%的PPh₃, 反应的结果也比在氩气氛围下得到的结果差(表 1, Entry 19).

  表 1

  

  表 1  反应条件优化^a

  Table 1.  optimized conditions

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  Entry	Cat.	Solvent	1a/2a	Yieldb/%	Time/h	3a-γ/3a-α
  1	PPh3	Toluene	1/2.0	82	18	2.3/1
  2	PPh3	Toluene	1/2.5	96	13	2.3/1
  3	PPh3	Toluene	1/3.0	96	13	2.3/1
  4	PBu3	Toluene	1/2.5	82	13	1/2.8
  5	PMe3	Toluene	1/2.5	18	24	1.1/1
  6	PCy3	Toluene	1/2.5	21	14	1/1
  7	Et3N	Toluene	1/2.5	n.d.	24
  8	AsPh3	Toluene	1/2.5	n.d.	24
  9c	PPh3	Toluene	1/2.5	65	14	1.7/1
  10d	PPh3	Toluene	1/2.5	59	14	1.7/1
  11	PPh3	CH3CN	1/2.5	12	24	5.3/1
  12	PPh3	CH3CH2OH	1/2.5	72	24	1.9/1
  13	PPh3	CH2Cl2	1/2.5	36	24	1.6/1
  14	PPh3	Tetrahydrofuran	1/2.5	Trace	24
  15e	PPh3	Toluene	1/2.5	57	24	2.4/1
  16 f	PPh3	Toluene	1/2.5	60	24	1.9/1
  17 g	PPh3	Toluene	1/2.5	47	24	1.7/1
  18h	PPh3	Toluene	1/2.5	40	24	2.0/1
  19h, i	PPh3	Toluene	1/2.5	65	38	1/1
  a All reactions were carried out by using 0.3 mmol of 1a, 2 mL of solvent; b Isolated yield; c 5 mol% PPh3 was used as catalyst; d 20 mol% PPh3 was used as catalyst; e The reaction was carried out at 25 ℃; f The reaction was carried out at 50 ℃; g The reaction was carried out at 110 ℃; h The reaction was carried out at air atmosphere; i After reacting for 24 h, additional 10 mol% PPh3 was added.

  至此, 我们确定了该反应的最佳条件为:橙酮(1a) 1.0 equiv., 联烯酸酯(2a) 2.5 equiv., PPh₃ 10 mol%, 溶剂为甲苯, 反应温度为35 ℃, 反应在氩气氛围下进行.

  1.2   反应底物拓展

  在获得该反应最优反应条件后, 反应底物的适用性研究随即进行(表 2).首先研究了底物橙酮类化合物R¹基团对反应的影响.先选定底物R¹基团为取代苯基, R²为氢时, 研究不同取代苯基基团对反应产率及区域选择性的影响(表 2, 3a~3g).通过实验结果可知, 橙酮上R¹为对位拉电子基团取代的苯基及对位甲基取代的苯基时, 反应底物1b~1d及1e, 在优化的反应条件下都能与联烯酸酯2a顺利反应.尽管反应的产率有些许地变化, 但总体而言, 反应都能以90%以上的分离总收率得到[3+2]环化产物.同时, 就反应区域选择性而言, 底物1b~1d得到的产物的区域选择性与模板底物的区域选择性相当, 都是以γ-选择性产物为主, α-选择性产物为次, 两者比例在2/1至3/1之间.这一结果表明R¹作为各类取代苯基时, 其对位上拉电子取代基对该反应的区域选择性影响不明显.然而, 当此类取代基为甲基时(1e), 该底物反应后不但得到了优异的环加成总产率(96%), 且反应的区域选择性也有所提高(γ/α＝5/1).基于此, 又进一步对苯环对位与间位用甲氧基取代的橙酮1f和1g进行了考察.然而, 这两个底物在反应24 h后, 仍有原料剩余.即使增加联烯酸酯2a的用量也无法使反应完全进行.最终1f和1g只能得到70%左右的产率, 且产物区域选择性也较之3e有所下降, 分别为3.7/1与2.8/1.以上结果初步表明该[3+2]环化反应受底物影响较大.然后, 又以R¹为其它的芳基基团对橙酮的反应情况进行研究.由结果可知, R¹基团无论是萘基(1h)、2-呋喃基(1i)或2-吡啶基(1j)的橙酮, 它们与联烯丁酸酯反应时, 都能完全转化, 生成环化产物.值得一提的是, 2-吡啶基取代的橙酮1j, 在该反应过程中, 尽管只得到了81%的产率, 但仅为γ-选择性的产物.遗憾的是, 尽管1h能在优化条件下得到环化产物, 但同时有未确定结构且与α-选择性产物无法分离的化合物形成.接下来, 又将R¹基团换为脂肪烃类取代基, 考察了底物的普适性.通过研究可知, R¹基因为肉桂基(1k)、环己基(1m)或叔丁基(1n)时, 反应均可进行, 但反应时间较长, 且产率降低严重. 1k在反应中的区域选择性为1.5/1, γ-选择性为主.而1m与1n也只得到γ-选择性产物, 并未观察到α-选择性产物.苯丙基取代的橙酮化合物1l在此反应条件下不反应, 只回收了原料.研究了橙酮中R¹基团后, 接下来又对橙酮中的R²基团进行了研究.当R¹为苯基, 向橙酮的6-位或7-位分别引入了甲基, 或向其5-位引入甲氧基(1o, 1p, 1q)时, 联烯酸酯2a分别与橙酮1o与1p反应, 能以不低于90%的产率得到相应的环化产物, 其区域选择性仍以γ-选择性为主, 比例分别为3.5/1与2.6/1.橙酮1q在相同的条件下反应, 产率却只有73%, 区域选择性比例为3q-γ/3q-α＝3.8/1.对比applanatumin A分子结构, 若要利用该策略对其进行合成, 则橙酮的R¹基团应考虑使用较大位阻的脂肪烃类取代基.因此, 又开展了R¹为叔丁基取代的橙酮化合物1r与1s在该反应条件下的适用性考察.通过反应研究可知, 这两个橙酮化合物都能与2a发生相应的[3+2]环化得到螺环产物.尽管, 它们的反应产率较低, 却只得到γ-选择性产物.这一结果的获得, 也为合成applanatumin A及其类似物提供了可能.随后, 筛查了联烯酸酯化合物酯基对该环化反应的影响.在得到联烯丁酸苄酯2b与联烯丁酸叔丁酯2c后, 使其分别与橙酮1a反应24 h后, 2b只能以45%的产率生成γ-选择性的环化产物3t-γ. 2c反应24 h后, 以73%的总产率也得到了γ-选择性及α-选择性两种产物3u-γ与3u-α, 其选择性比例为2.1/1.最后, 橙酮中双键的立体构型对环化反应的影响也给予了初步的考察.当使用(E)-橙酮1v时, 能与联烯酸酯2a发生环化反应.在反应12 h后, 以57%的分离收率得到环化产物.然而, 通过核磁鉴定可知, 该反应只得到了α-选择性产物.与3a-α比较后, 该环化产物被确认为非对映异构体3v-α.

  表 2

  

  表 2  反应底物拓展^{a, b}

  Table 2.  Scope of substrates

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  a All reactions were carried out by using 0.3 mmol of 1, 0.75 mmol of 2, 2 mL of toluene as solvent; b Isolated yield; c (E)-2-Benzylidenebenzofuran-3(2H)-one was used in the reaction.

  由于天然产物applanatumin A及其类似物中的结构单元为螺[1-苯并呋喃-3-酮-2, 2'-环戊烷], 因此在得到初步的[3+2]环化反应结果后, 又进行了环化产物螺[1-苯并呋喃-3-酮-2, 5'-环戊烯]的还原, 以期得到螺[1-苯并呋喃-3-酮-2, 2'-环戊烷]结构骨架.在选择了环化产物3r-γ和3s-γ作为衍生化底物后, 将其分别置于氢气/Pd/C条件下还原, 反应14 h后便分别以74%和80%的产率得到还原产物4r-γ和4s-γ.这样的结果为后续的天然产物合成研究提供了很好的反应探索(Scheme 1).

  图式 1

  

  图式 1.  环化产物的还原

  Scheme 1.  Reduction of the annulated compounds

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  基于大量的文献报道事实^[8a], 该反应的可能机理也应该为一典型的陆氏[3+2]环化反应(Scheme 2).首先PPh₃作为经典的膦亲核试剂加成至联烯酸酯2a的β位, 形成两性离子中间体A.该中间体存在两种共振形式B-α和B-γ, 并以此两种形式分别与橙酮1a反应构筑第一次的C—C键, 形成α-加成中间体C-α和γ-加成中间体C-γ.随后, 该中间体再各自发生分子内的加成环化形成第二次的C—C键后得到相应的螺环产物D-α和D-γ这两个螺环中间体在体系中微量水的作用下, 各自捕获质子后再发生酯基α位的质子离去, 从而实现螺环中间体的1, 2-质子转移过程, 分别形成消除前体化合物F-α和F-γ最后, F-α和F-γ发生消除形成C—C键, 得到最终的环化产物3a-α和3a-γ.同时, 反应释放出催化剂PPh₃使其参与到后续的催化循环中.

  图式 2

  

  图式 2.  可能的反应机理

  Scheme 2.  A possible mechanism

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  2.   结论

  综上所述, 在PPh₃的催化下, 橙酮和联烯酸酯可发生[3+2]环化反应, 以γ-选择性和α-选择性同时得到两个螺环化合物.其中γ-选择性环化产物为主要产物, 且其具有螺[1-苯并呋喃-3-酮-2, 5'-环戊稀]单元.该结构单元是天然产物applanatumin A及其类似物的重要母核结构.该方法学的建立必将为此类天然产物的合成奠定良好的方法学基础.

  3.   实验部分

  3.1   仪器与试剂

  核磁共振谱用Varian Mercury 400 plus或Agilent DD₂ 600型核磁共振仪测定, 以氘代氯仿作为溶剂, TMS为内标; 高分辨质谱用Thermo Qtof Agilent 6540, QP-IO00AGC-MS或Q EXACTIVE 测定, ESI源; 熔点测定用显微熔点测定仪测定, 温度未校正; 太阳光用模拟日光氙灯光源CEL-S500照射.

  实验中所用原料1a~1r^[9], 1v^[10], 2a~2c^[11]是根据文献自制; 四氢呋喃(THF)、乙腈、二氯甲烷、三氯甲烷、甲苯按标准程序处理, 蒸馏备用, 其它试剂均为国产分析纯级试剂.

  3.2   实验方法

  3.2.1   (E)-2-亚苄基苯并呋喃-3(2H)-酮(1v)的制备

  在50 mL圆底烧瓶中, 加入橙酮1a (0.45 mmol, 100 mg), Ar置换三次, 将其溶于25 mL三氯甲烷后, 将整个反应体系置于日光氙灯(22 mA)下搅拌, 薄层色谱(TLC)监测.反应18 h后, 减压除去溶剂.残留物进行柱层析[V(石油醚):V(甲基叔丁基醚)＝9:1]分离得产物1v.

  3.2.2   3-氧代-4'-苯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3a-γ)和3-氧代-5'-苯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3a-α)的制备

  在10 mL反应管中, 加入橙酮1a (0.3 mmol, 67 mg, 1.0 equiv.), PPh₃ (0.03 mmol, 8 mg, 10%), Ar置换三次.然后向反应体系中加入2 mL甲苯作为溶剂后, 再向反应体系中加入联烯酸乙酯2a (0.75 mmol, 84 mg, 2.5 equiv.).随后, 将整个反应体系置于35 ℃下搅拌反应. TLC监测, 待反应完全后, 减压除去溶剂.残留物进行柱层析[V(石油醚):V(乙酸乙酯)＝10 : 1]分离得产物3a-γ和3a-α.其余化合物制备方法同3a-γ和3a-α.

  3.2.3   3'-(叔丁基)-7-甲基-3-氧代-3H-螺[苯并呋喃-2, 2'-环戊烷]-1'-羧酸乙酯(4r-γ)的制备

  在10 mL圆底烧瓶中, 加入3r-γ (0.2 mmol, 66 mg, 1.0 equiv.)后, 用2 mL甲醇溶解.向此反应体系中加入Pd/C (6.6 mg, 10%), 并通入氢气. TLC监测, 待反应完全后, 过滤除去Pd/C, 浓缩滤液后得到残留物.残留物进行柱层析[V(石油醚):V(乙酸乙酯)＝20:1]分离得产物4r-γ.化合物4s-γ制备方法同4r-γ.

  (E)-2-亚苄基苯并呋喃-3(2H)-酮(1v): 黄色固体, 58 mg, 产率58%. m.p. 133~135 ℃ (Lit.^[10] 178 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 8.18~8.16 (m, 2H), 7.80~7.79 (m, 1H), 7.65~7.61 (m, 1H), 7.46~7.42 (m, 3H), 7.22~7.16 (m, 2H), 6.97 (s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 182.7, 165.3, 148.1, 136.8, 131.8, 130.9, 130.3, 128.4, 124.6, 123.3, 122.7, 122.6, 112.6.

  3-氧代-4'-苯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯- 1'-羧酸乙酯(3a-γ): 白色固体, 67 mg, 产率67%. m.p. 81~85 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.59~7.57 (m, 1H), 7.46 (t, J＝2.4 Hz, 1H), 7.42~7.37 (m, 1H), 7.19~7.09 (m, 5H), 6.92 (t, J＝8.0 Hz, 1H), 6.76 (d, J＝8.4 Hz, 1H), 4.06~3.98 (m, 3H), 3.18~3.03 (m, 2H), 0.96 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.8, 170.8, 162.2, 152.1, 137.6, 135.1, 134.7, 129.0, 127.9, 127.4, 123.8, 121.9, 121.5, 112.5, 96.8, 60.7, 53.9, 38.2, 13.6; HRMS (ESI) calcd for C₂₁H₁₉O₄ [M+H]⁺ 335.1278, found 335.1281.

  3-氧代-5'-苯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯- 1'-羧酸乙酯(3a-α): 黄色固体, 29 mg, 产率29%. m.p. 73~75 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.61~7.59 (m, 1H), 7.42~7.40 (m, 1H), 7.13~7.08 (m, 3H), 6.99~6.95 (m, 4H), 6.67 (d, J＝8.4 Hz, 1H), 4.57 (s, 1H), 4.12~3.99 (m, 2H), 3.18~3.14 (m, 1H), 2.94~2.90 (m, 1H), 1.05 (t, J＝6.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 202.5, 171.2, 163.7, 140.4, 138.2, 136.9, 135.0, 128.5, 127.6, 127.0, 124.1, 121.8, 120.6, 112.8, 95.4, 60.3, 59.4, 41.9, 13.9; HRMS (ESI) calcd for C₂₁H₁₈O₄Na [M+Na]⁺ 357.10973, found 357.10977.

  4'-(4-氟苯基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3b-γ): 白色固体, 63 mg, 产率59%. m.p. 63~65 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 3.58~7.57 (m, 1H), 7.45~7.41 (m, 2H), 7.16~7.14 (m, 2H), 6.95 (t, J＝7.2 Hz, 1H), 6.83 (t, J＝9.0 Hz, 2H), 6.78 (d, J＝8.4 Hz, 1H), 4.06~3.96 (m, 3H), 3.08~3.06 (m, 2H), 0.96 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.6, 170.7, 162.8, 162.1, 161.2, 151.9, 137.8, 134.8, 130.9, 130.9 130.6, 130.5, 123.8, 121.8, 121.6, 114.9, 114.7, 112.5, 96.6, 60.8, 53.2, 38.5, 13.6; HRMS (ESI) calcd for C₂₁H₁₈FO₄ [M+H]⁺ 353.1184, found 353.1186.

  5'-(4-氟苯基)-3-氧代-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3b-α): 黄色固体, 32 mg, 产率31%. m.p. 96~100 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.60~7.59 (m, 1H), 7.46~7.43 (m, 1H), 7.00~6.96 (m, 4H), 6.82 (t, J＝8.4 Hz, 2H), 6.70 (d, J＝9.0 Hz, 1H), 4.56 (s, 1H), 4.13~4.00 (m, 2H), 3.18~3.14 (m, 1H), 2.93~2.89 (m, 1H), 1.07 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.2, 171.1, 163.5, 162.7, 161.1, 140.6, 138.3, 136.7, 130.8, 130.8, 130.1, 130.1, 124.1, 122.0, 120.6, 114.6, 114.4, 112.8, 94.9, 60.4, 58.8, 41.8, 13.9; HRMS (ESI) calcd for C₂₁H₁₆FO₄ [M－H]^－ 351.10381, found 351.10391.

  4'-(4-氯苯基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3c-γ): 黄色固体, 79 mg, 产率72%. m.p. 101~104 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.59~7.57 (m, 1H), 7.45~7.42 (m, 2H), 7.12 (s, 4H), 6.96 (t, J＝7.2 Hz, 1H), 6.79 (d, J＝8.4 Hz, 1H), 4.05~3.99 (m, 2H), 3.96 (t, J＝8.4, 1H), 3.08~3.06 (m, 2H), 0.96 (t, J＝6.6 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.5, 170.7, 162.0, 151.8, 137.9, 134.8, 133.8, 133.2, 130.3, 128.1, 123.8, 121.8, 121.7, 112.6, 96.5, 60.8, 53.1, 38.4, 13.5; HRMS (ESI) calcd for C₂₁H₁₈ClO₄ [M+H]⁺ 369.0888, found 369.0888.

  5'-(4-氯苯基)-3-氧代-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3c-α): 黄色固体, 26 mg, 产率23%. m.p. 110~112 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.61~7.59 (m, 1H), 7.48~7.44 (m, 1H), 7.11 (d, J＝8.4 Hz, 2H), 7.02~6.98 (m, 2H), 6.94 (d, J＝8.4 Hz, 2H), 6.72 (d, J＝8.4 Hz, 1H), 4.55 (s, 1H), 4.14~4.00 (m, 2H), 3.19~3.13 (m, 1H), 2.94~2.88 (m, 1H), 1.08 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.1, 171.1, 163.5, 140.8, 138.4, 136.5, 133.7, 132.8, 129.9, 127.8, 124.2, 122.1, 120.5, 112.9, 94.8, 60.5, 58.7, 42.0, 14.0; HRMS (ESI) calcd for C₂₁H₁₈ClO₄ [M+H]⁺ 369.0888, found 369.0887.

  4'-(4-溴苯基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3d-γ): 白色固体, 74 mg, 产率61%. m.p. 110~113 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.60~7.57 (m, 1H), 7.47~7.42 (m, 2H), 7.29~7.26 (m, 2H), 7.06 (d, J＝8.8 Hz, 2H), 6.97 (t, J＝6.8 Hz, 1H), 6.7 9 (d, J＝8.4 Hz, 1H), 4.06~3.97 (m, 2H), 3.95 (t, J＝8.4 Hz, 1H), 3.08~3.05 (m, 2H), 0.95 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.5, 170.7, 162.1, 151.8, 137.9, 134.8, 134.3, 131.1, 130.7, 123.8, 121.8, 121.4, 112.6, 110.0, 96.5, 60.8, 53.2, 38.4, 13.6; HRMS (ESI) calcd for C₂₁H₁₈BrO₄ [M+H]⁺ 413.0383, found 413.0376.

  5'-(4-溴苯基)-3-氧代-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3d-α): 白色固体, 37 mg, 产率29%. m.p. 72~74 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.61~7.60 (m, 1H), 7.48~7.45 (m, 1H), 7.26 (d, J＝8.4 Hz, 2H), 7.01~6.99 (m, 2H), 6.86 (d, J＝8.4 Hz, 2H), 6.72 (d, J＝9.0 Hz, 1H), 4.53 (s, 1H), 4.12~4.01 (m, 2H), 3.17~3.14 (m, 1H), 2.93~2.89 (m, 1H), 1.09 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.1, 171.1, 163.4, 140.8, 138.4, 136.5, 134.3, 130.8, 130.3, 124.2, 122.1, 121.0, 120.5, 112.9, 94.7, 60.5, 58.8, 42.0, 14.0; HRMS (ESI) calcd for C₂₁H₁₆BrO₄ [M－H]^－ 411.0237, found 411.0237.

  3-氧代-4'-(对甲苯基)-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3e-γ): 白色固体, 84 mg, 产率80%. m.p. 88~89 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.59~7.58 (m, 1H), 7.45 (t, J＝2.4 Hz, 1H), 7.43~7.38 (m, 1H), 7.06 (d, J＝8.0 Hz, 2H), 6.96~6.91 (m, 3H), 6.78 (d, J＝8.4 Hz, 1H), 4.04~3.95 (m, 3H), 3.09~3.05 (m, 2H), 2.20 (s, 3H), 0.95 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.9, 170.9, 162.2, 152.2, 137.6, 136.9, 134.8, 132.1, 128.9, 128.6, 123.7, 121.9, 121.4, 112.6, 96.8, 60.7, 53.6, 38.4, 21.0, 13.5; HRMS (ESI) calcd for C₂₂H₂₀NaO₄ [M+Na]⁺ 371.1259, found 371.1251.

  3-氧代-5'-(对甲苯基)-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3e-α): 白色固体, 17 mg, 产率16%. m.p. 75~75 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.61~7.60 (m, 1H), 7.44~7.41 (m, 1H), 6.99~6.96 (m, 2H), 6.93 (d, J＝7.8 Hz, 2H), 6.87 (d, J＝7.8 Hz, 2H), 6.71 (d, J＝8.4 Hz, 1H), 4.54 (s, 1H), 4.12~4.01 (m, 2H), 3.15~3.11 (m, 1H), 2.93~2.89 (m, 1H), 2.22 (s, 3H), 1.08 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.6, 171.2, 163.7, 140.0, 138.1, 137.1, 136.5, 132.0, 128.4, 128.4, 124.1, 121.8, 120.6, 112.9, 95.0, 60.3, 58.9, 41.9, 21.1, 14.0; HRMS (ESI) calcd for C₂₂H₂₁O₄ [M+ H]⁺ 349.1434, found 349.1435.

  4'-(4-甲氧基苯基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3f-γ): 黄色液体, 60 mg, 产率55%. ¹H NMR (600 MHz, CDCl₃) δ: 7.58~7.56 (m, 1H), 7.45 (t, J＝2.4 Hz, 1H), 7.42~7.39 (m, 1H), 7.10 (d, J＝9.0 Hz, 2H), 6.92 (t, J＝7.2 Hz, 1H), 6.79 (d, J＝8.4 Hz, 1H), 6.67 (d, J＝9.0 Hz, 2H), 4.04~3.98 (m, 2H), 3.95 (t, J＝7.8 Hz, 1H), 3.68 (s, 3H), 3.06~3.04 (m, 2H), 0.95 (t, J＝7.2, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 201.9, 170.8, 162.2, 158.7, 152.2, 137.6, 134.7, 130.0, 127.1, 123.7, 121.9, 121.4, 113.3, 112.5, 96.8, 60.7, 55.0, 53.3, 38.5, 13.5; HRMS (ESI) calcd for C₂₂H₂₁O₅ [M+H]⁺ 365.1384, found 365.1385.

  5'-(4-甲氧基苯基)-3-氧代-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3f-α): 黄色液体, 16 mg, 产率16%. ¹H NMR (600 MHz, CDCl₃) δ: 7.60~7.59 (m, 1H), 7.45~7.42 (m, 1H), 6.99~6.95 (m, 2H), 6.92 (d, J＝8.4 Hz, 2H), 6.72 (d, J＝8.4 Hz, 1H), 6.66 (d, J＝8.4 Hz, 2H), 4.53 (s, 1H), 4.12~4.01 (m, 2H), 3.70 (s, 3H), 3.16~3.12 (m, 1H), 2.92~2.89 (m, 1H), 1.08 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.6, 171.2, 163.7, 158.5, 140.1, 138.2, 137.1, 129.6, 127.2, 124.1, 121.8, 120.6, 113.1, 112.9, 95.2, 60.3, 58.7, 55.1, 41.8, 14.0; HRMS (ESI) calcd for C₂₂H₁₉O₅ [M－H]^－ 363.1238, found 363.1238.

  4'-(3-甲氧基苯基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3g-γ): 黄色液体, 57 mg, 产率52%. ¹H NMR (600 MHz, CDCl₃) δ: 7.60~7.58 (m, 1H), 7.45 (t, J＝1.8 Hz, 1H), 7.41 (t, J＝7.2 Hz, 1H), 7.05 (t, J＝7.8 Hz, 1H), 6.94 (t, J＝7.2 Hz, 1H), 6.79~6.76 (m, 2H), 6.71 (s, 1H), 6.66~6.65 (m, 1H), 4.04~3.97 (m, 3H), 3.66 (s, 3H), 3.15~3.03 (m, 2H), 0.96 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.8, 170.9, 162.1, 159.1, 152.0, 137.6, 136.7, 134.7, 128.8, 123.7, 121.9, 121.5, 121.3, 114.4, 113.1, 112.5, 96.7, 60.7, 55.1, 53.7, 38.1, 13.5; HRMS (ESI) calcd for C₂₂H₂₁O₅ [M+H]⁺ 365.1384, found 365.1382.

  5'-(3-甲氧基苯基)-3-氧代-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3g-α): 黄色液体, 20 mg, 产率19%. ¹H NMR (600 MHz, CDCl₃) δ: 7.62~7.61 (m, 1H), 7.45~7.42 (m, 1H), 7.04 (t, J＝7.8 Hz, 1H), 7.00~6.97 (m, 2H), 6.71 (d, J＝8.4 Hz, 1H), 6.66 (dd, J＝7.8 Hz, J＝1.8 Hz 1H), 6.59 (d, J＝7.2 Hz, 1H), 6.52 (s, 1H), 4.55 (s, 1H), 4.13~4.02 (m, 2H), 3.65 (s, 3H), 3.16~3.12 (m, 1H), 2.94~2.90 (m, 1H), 1.08 (t, J＝6.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 202.5, 171.3, 163.7, 159.0, 140.3, 138.2, 136.8, 136.6, 128.6, 124.2, 121.8, 121.1, 120.6, 114.0, 112.9, 112.9, 94.9, 60.4, 59.2, 55.1, 41.9, 14.0; HRMS (ESI) calcd for C₂₂H₁₉O₅ [M－H]^－ 363.1238, found 363.1239.

  4'-(萘-1-基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3h-γ): 白色固体, 80 mg, 产率69%. m.p. 158~161 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.97 (d, J＝8.4 Hz, 1H), 7.70 (d, J＝8.4 Hz, 1H), 7.65 (d, J＝7.8 Hz, 1H), 7.59 (d, J＝7.2 Hz, 1H), 7.55 (t, J＝3.0 Hz, 1H), 7.44~7.38 (m, 3H), 7.36~7.33 (m, 1H), 7.28~7.25 (m, 1H), 6.78 (t, J＝7.8 Hz, 1H), 6.63 (d, J＝8.4 Hz, 1H), 4.93 (t, J＝7.8 Hz, 1H), 4.07~3.99 (m, 2H), 3.30~3.19 (m, 2H), 0.95 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.1, 171.0, 162.3, 152.0, 137.5, 134.8, 133.5, 132.1, 131.8, 128.6, 127.9, 127.6, 126.2, 125.3, 124.7, 123.8, 123.2, 121.6, 121.4, 112.3, 96.6, 60.7, 47.5, 40.0, 13.5; HRMS (ESI) calcd for C₂₅H₂₁O₄ [M+H]⁺ 385.1434, found 385.1437.

  4'-(呋喃-2-基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3i-γ): 黄色粘稠液体, 47 mg, 产率48%. ¹H NMR (600 MHz, CDCl₃) δ: 7.69~7.68 (m, 1H), 7.50 (t, J＝7.2 Hz, 1H), 7.40 (t, J＝2.4 Hz, 1H), 7.15 (s, 1H), 7.03 (t, J＝7.2 Hz, 1H), 6.86 (d, J＝8.4 Hz, 1H), 6.16~6.15 (m, 1H), 6.03 (d, J＝3.6 Hz, 1H), 4.10 (t, J＝7.8 Hz, 1H), 4.05~3.96 (m, 2H), 3.20 (ddd, J＝18.6 Hz, J＝8.4 Hz, J＝2.4 Hz, 1H), 3.06 (ddd, J＝19.2 Hz, J＝8.4 Hz, J＝3.0 Hz, 1H), 0.95 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.4, 171.3, 161.9, 151.4, 150.0, 141.9, 137.7, 134.8, 124.0, 121.7, 121.6, 112.5, 110.0, 107.7, 96.3, 60.7, 46.7, 35.7, 13.5; HRMS (ESI) calcd for C₁₉H₁₇O₅ [M+H]⁺ 325.1071, found 325.1079.

  5'-(呋喃-2-基)-3-氧代-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3i-α): 黄色粘稠液体, 40 mg, 产率40%. ¹H NMR (600 MHz, CDCl₃) δ: 7.66~7.65 (m, 1H), 7.54~7.51 (m, 1H), 7.24 (s, 1H), 7.05 (t, J＝7.2 Hz, 1H), 6.99~6.97 (m, 1H), 6.87 (d, J＝8.4 Hz, 1H), 6.17~6.17 (m, 1H), 5.96 (d, J＝3.0 Hz, 1H), 4.66 (s, 1H), 4.19~4.08 (m, 2H), 3.13~3.10 (m, 1H), 2.98~2.94 (m, 1H), 1.16 (t, J＝7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 202.0, 171.5, 163.2, 149.2, 141.8, 140.6, 138.3, 134.6, 124.3, 122.1, 120.1, 113.0, 110.0, 107.9, 94.7, 60.5, 52.3, 41.7, 14.0; HRMS (ESI) calcd for C₁₉H₁₇O₅ [M+H]⁺ 325.1071, found 325.1069.

  3-氧代-4'-(吡啶-2-基)-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3j-γ): 白色固体, 81 mg, 产率81%. mp 108~111 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.45~8.43 (m, 1H), 7.68~7.66 (m, 1H), 7.48 (t, J＝2.4 Hz, 1H), 7.43~7.38 (m, 2H), 7.04~6.94 (m, 3H), 6.69 (d, J＝8.0 Hz, 1H), 4.24 (t, J＝7.6 Hz, 1H), 4.05~3.94 (m, 2H), 3.66 (ddd, J＝28.2 Hz, J＝11.4 Hz, J＝3.0 Hz, 1H), 3.05 (ddd, J＝28.2 Hz, J＝12.0 Hz, J＝4.8 Hz, 1H), 0.94 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.8, 170.9, 162.0, 155.3, 152.4, 148.9, 137.5, 135.8, 134.1, 123.8, 122.9, 122.1, 122.0, 121.5, 112.3, 97.1, 60.6, 54.8, 35.4, 13.5; HRMS (ESI) calcd for C₂₀H₁₈NO₄ [M+H]⁺ 336.1230, found 336.1235.

  (E)-3-氧代-4'-苯乙烯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3k-γ): 白色固体, 27 mg, 产率25%. mp 88~89 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.65 (d, J＝7.2 Hz, 1H), 7.56 (t, J＝8.4 Hz, 1H), 7.23~7.19 (m, 4H), 7.17~7.14 (m, 1H), 7.03 (t, J＝8.4 Hz, 2H), 6.89~6.88 (m, 1H), 6.34 (d, J＝16.8, 1H), 6.12 (dd, J＝15.6 Hz, J＝6 Hz, 1H), 4.23~4.12 (m, 3H), 3.10~3.06 (m, 1H), 2.89~2.85 (m, 1H), 1.22 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.4, 171.5, 163.7, 139.7, 138.5, 137.0, 136.6, 133.6, 128.3, 127.3, 126.3, 124.4, 123.8, 122.1, 120.8, 113.1, 96.3, 60.5, 56.5, 42.1, 14.2; HRMS (ESI) calcd for C₂₃H₂₁O₄ [M+H]⁺ 361.1434, found 361.1432.

  (E)-3-氧代-5'-苯乙烯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3k-α): 黄色固体, 18 mg, 产率16%. m.p. 103~105 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.63~7.61 (m, 1H), 7.34 (d, J＝7.2 Hz, 2H), 7.28~7.26 (m, 3H) 7.19 (t, J＝7.2 Hz, 1H), 7.08 (dd, J＝17.4 Hz, J＝9.6 Hz, 2H), 6.95 (s, 1H), 6.39 (d, J＝15.6 Hz, 1H), 6.12 (dd, J＝15.6 Hz, J＝9.6 Hz, 1H), 4.25~4.13 (m, 2H), 3.97 (d, J＝9.6 Hz, 1H), 3.29~3.25 (m, 1H), 2.80 (dd, J＝18.6 Hz, J＝3.0 Hz, 1H), 1.26 (t, J＝6.6 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 199.6, 171.0, 163.4, 139.6, 138.1, 136.9, 136.8, 132.8, 128.4, 127.5, 126.6, 124.6, 124.4, 122.1, 121.1, 113.3, 97.0, 60.5, 58.3, 42.1, 14.2; HRMS (ESI) calcd for C₂₃H₁₉O₄ [M－H]^－ 359.1289, found 359.1294.

  4'-环己基-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3m-γ): 白色固体, 31 mg, 产率30%. m.p. 109~111 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.70 (d, J＝7.2 Hz, 1H), 7.60~7.59 (m, 1H), 7.32 (t, J＝3.0 Hz, 1H), 7.09~7.04 (m, 2H), 4.00~3.90 (m, 2H), 2.78~2.73 (m, 1H), 2.65~2.55 (m, 2H), 1.76~1.67 (m, 2H), 1.63~1.52 (m, 2H), 1.42~1.40 (m, 1H), 1.23~1.16 (m, 1H), 1.13~1.11 (m, 1H), 1.09~1.04 (m, 1H), 1.02~0.94 (m, 2H), 0.90 (t, J＝7.2 Hz, 3H), 0.79~0.72 (m, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.7, 171.5, 162.3, 151.9, 137.4, 135.8, 124.1, 122.4, 121.6, 112.4, 97.2, 60.5, 53.8, 37.1, 35.9, 32.4, 31.4, 26.1, 26.1, 25.7, 13.5; HRMS (ESI) calcd for C₂₁H₂₅O₄ [M+H]⁺ 341.1747, found 341.1748.

  4'-(叔丁基)-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3n-γ): 白色固体, 47 mg, 产率50%. m.p. 88~89 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.73~7.71 (m, 1H), 7.63~7.58 (m, 1H), 7.35 (t, J＝1.6 Hz, 1H), 7.10~7.04 (m, 2H), 4.00~3.87 (m, 2H), 2.81~2.65 (m, 3H), 0.91~0.87 (m, 12H); ¹³C NMR (150 MHz, CDCl₃) δ: 203.1, 171.1, 162.2, 151.7, 137.4, 135.8, 124.1, 122.4, 121.6, 112.5, 98.2, 60.5, 57.7, 33.9, 33.0, 28.7, 13.5; HRMS (ESI) calcd for C₁₉H₂₂NaO₄ [M+Na]⁺ 337.1416, found 337.1404.

  6-甲基-3-氧代-4'-苯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3o-γ): 白色固体, 77 mg, 产率73%. m.p. 102~105 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.46~7.44 (m, 2H), 7.19~7.11 (m, 5H), 6.74 (d, J＝8.4 Hz, 1H), 6.56 (s, 1H), 4.05~3.98 (m, 3H), 3.15~3.04 (m, 2H), 2.28 (s, 3H), 0.99 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.1, 171.4, 162.3, 151.9, 149.6, 135.4, 134.9, 129.0, 127.9, 127.3, 123.4, 123.1, 119.5, 112.6, 97.1, 60.7, 53.7, 38.3, 22.4, 13.6; HRMS (ESI) calcd for C₂₂H₂₁O₄ [M+H]⁺ 349.1434, found 349.1437.

  6-甲基-3-氧代-5'-苯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3o-α): 白色固体, 21 mg, 产率21%. m.p. 100~102 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.48 (d, J＝7.8 Hz, 1H), 7.15~7.09 (m, 3H), 7.01~6.98 (m, 3H), 6.78 (d, J＝7.2 Hz, 1H), 6.48 (s, 1H), 4.57 (s, 1H), 4.11~3.98 (m, 2H), 3.15~3.11 (m, 1H), 2.91~2.87 (m, 1H), 2.28 (s, 3H), 1.04 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.7, 171.7, 163.7, 150.3, 140.3, 137.0, 135.2, 128.6, 127.6, 126.9, 123.7, 123.5, 118.1, 112.8, 95.2, 60.3, 59.1, 42.1, 22.4, 13.9; HRMS (ESI) calcd for C₂₂H₂₁O₄ [M+H]⁺ 349.1434, found 349.1433.

  7-甲基-3-氧代-4'-苯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3p-γ): 白色固体, 68 mg, 产率65%. m.p. 104~107 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.46 (t, J＝2.4 Hz, 1H), 7.39 (d, J＝7.8 Hz, 1H), 7.17 (t, J＝7.2 Hz, 3H), 7.14~7.08 (m, 3H), 6.80 (t, J＝7.2 Hz, 1H), 4.07~4.00 (m, 2H), 3.97 (t, J＝7.8 Hz, 1H), 3.16~3.05 (m, 2H), 2.05 (s, 3H), 0.98 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.3, 169.6, 162.2, 152.1, 137.9, 135.3, 134.8, 129.0, 127.7, 127.3, 122.6, 121.3, 121.2, 120.9, 96.6, 60.7, 54.0, 38.4, 14.1, 13.6; HRMS (ESI) calcd for C₂₂H₂₁O₄ [M+H]⁺ 349.1434, found 349.1439.

  7-甲基-3-氧代-5'-苯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3p-α): 黄色油状液体, 26 mg, 产率25%. ¹H NMR (600 MHz, CDCl₃) δ: 7.42 (d, J＝7.2 Hz, 1H), 7.19 (d, J＝7.2 Hz, 1H), 7.10~7.09 (m, 3H), 7.01~6.98 (m, 3H), 6.85 (t, J＝7.2 Hz, 1H), 4.55 (s, 1H), 4.12~3.99 (m, 2H), 3.20~3.17 (m, 1H), 2.94~2.90 (m, 1H), 1.89 (s, 3H), 1.04 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.8, 170.0, 163.7, 140.6, 138.3, 136.7, 135.1, 128.5, 127.4, 126.9, 123.2, 121.6, 121.2, 120.1, 94.8, 60.3, 59.8, 41.8, 13.9, 13.8; HRMS (ESI) calcd for C₂₂H₂₁O₄ [M+H]⁺ 349.1434, found 349.1430.

  5-甲氧基-3-氧代-4'-苯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3q-γ): 黄色油状液体, 65 mg, 产率59%. ¹H NMR (600 MHz, CDCl₃) δ: 7.44 (t, J＝7.2 Hz, 1H), 7.18~7.10 (m, 5H), 7.02 (dd, J＝9.0 Hz, J＝6.0 Hz, 1H), 6.85 (d, J＝2.4 Hz, 1H), 6.68 (d, J＝9.0 Hz, 1H), 4.08~4.01 (m, 2H), 3.98 (t, J＝7.8 Hz, 1H), 3.73 (s, 3H), 3.15~3.04 (m, 2H), 1.02 (t, J＝7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 202.1, 166.2, 162.2, 154.5, 151.9, 135.1, 134.9, 129.0, 127.9, 127.5, 121.7, 113.4, 103.7, 97.5, 60.7, 55.7, 54.0, 38.2, 13.7; HRMS (ESI) calcd for C₂₂H₂₁O₅ [M+H]⁺ 365.1384, found 365.1386.

  5-甲氧基-3-氧代-5'-苯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯-1'-羧酸乙酯(3q-α): 黄色油状液体, 17 mg, 产率16%. ¹H NMR (600 MHz, CDCl₃) δ: 7.14~7.10 (m, 3H), 7.05 (dd, J＝9.0 Hz, J＝3.0 Hz, 1H), 6.99~6.98 (m, 4H), 6.60 (d, J＝9.0 Hz, 1H), 4.56 (s, 1H), 4.11~3.99 (m, 2H), 3.75 (s, 3H), 3.17~3.13 (m, 1H), 2.93~2.89 (m, 1H), 1.04 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.6, 166.6, 163.7, 154.8, 140.4, 136.9, 135.1, 128.5, 128.3, 127.6, 127.0, 120.4, 113.7, 103.7, 95.8, 60.3, 59.5, 55.8, 41.9, 13.9; HRMS (ESI) calcd for C₂₂H₁₉O₅ [M－H]^－ 363.1238, found 363.1240.

  4'-(叔丁基)-7-甲基-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3r-γ): 白色固体, 25 mg, 产率25%. m.p. 92~96 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.54 (d, J＝7.2 Hz, 1H), 7.41 (d, J＝7.2 Hz, 1H), 7.34 (t, J＝7.2 Hz, 1H), 6.98 (t, J＝7.2 Hz, 1H), 4.00~3.87 (m, 2H), 2.81~2.66 (m, 3H), 2.29 (s, 3H), 0.90~0.88 (m, 12H); ¹³C NMR (150 MHz, CDCl₃) δ: 203.7, 170.0, 162.3, 151.6, 137.9, 135.9, 122.5, 121.7, 121.5, 121.3, 98.1, 60.4, 57.6, 33.9, 33.0, 28.7, 14.4, 13.5; HRMS (ESI) calcd for C₂₀H₂₅O₄ [M+H]⁺ 329.1474, found 329.1474.

  4'-(叔丁基)-5-甲氧基-3-氧代-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯-1'-羧酸乙酯(3s-γ): 白色固体, 36 mg, 产率35%. m.p. 96~100 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.33~7.32 (m, 1H), 7.23 (dd, J＝8.8 Hz, J＝2.8 Hz, 1H), 7.14 (d, J＝2.4 Hz, 1H), 6.97 (d, J＝8.8 Hz, 1H), 4.03~3.90 (m, 2H), 3.82 (s, 3H), 2.81~2.66 (m, 3H), 0.96 (t, J＝7.2 Hz, 3H), 0.88 (s, 9H); ¹³C NMR (150 MHz, CDCl₃) δ: 203.4, 166.4, 162.2, 154.8, 151.5, 135.9, 127.1, 122.2, 113.4, 104.4, 99.0, 60.5, 57.8, 55.9, 33.9, 33.0, 28.7, 13.6; HRMS (ESI) calcd for C₂₀H₂₅O₅ [M+H]⁺ 345.1697, found 345.1695.

  3-氧代-4'-苯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯- 1'-羧酸苄基酯(3t-γ): 黄色固体, 54 mg, 产率45%. m.p. 72~75 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.52 (t, J＝2.4 Hz, 1H), 7.47 (d, J＝7.8 Hz, 1H), 7.37~7.34 (m, 1H), 7.24~7.20 (m, 3H), 7.17~7.08 (m, 5H), 7.07~7.04 (m, 2H), 6.87 (t, J＝7.2 Hz, 1H), 6.71 (d, J＝8.4 Hz, 1H), 5.05 (d, J＝12.0 Hz, 1H), 4.97 (d, J＝12.6 Hz, 1H), 3.99 (t, J＝8.4 Hz, 1H), 3.18~3.05 (m, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.7, 170.7, 162.0, 153.0, 137.6, 135.1, 135.0, 134.4, 129.0, 128.4, 128.0, 128.0, 127.9, 127.4, 123.8, 121.8, 121.5, 112.5, 96.7, 66.6, 54.1, 38.2; HRMS (ESI) calcd for C₂₆H₂₁O₄ [M+H]⁺ 397.1434, found 397.1434.

  3-氧代-4'-苯基-3H-螺[苯并呋喃-2, 5'-环戊烷]-2'-烯- 1'-羧酸叔丁酯(3u-γ)^[2b]: 黄色液体, 54 mg, 产率49%. ¹H NMR (600 MHz, CDCl₃) δ: 7.56 (d, J＝7.8 Hz, 1H), 7.42~7.38 (m, 2H), 7.17~7.09 (m, 5H), 6.91 (t, J＝7.8 Hz, 1H), 6.76 (d, J＝8.4 Hz, 1H), 3.98 (t, J＝8.4 Hz, 1H), 3.12~3.01 (m, 2H), 1.15 (s, 9H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.0, 170.9, 161.4, 151.7, 137.6, 136.0, 135.3, 129.0, 127.9, 127.3, 123.8, 122.1, 121.4, 112.5, 96.8, 81.6, 54.2, 38.0, 27.6; HRMS (ESI): calcd for C₂₃H₂₂NaO₄ [M+Na]⁺ 385.1416, found 385.1417.

  3-氧代-5'-苯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯- 1'-羧酸叔丁酯(3u-α)^[2b]: 黄色液体, 25 mg, 产率24%. ¹H NMR (600 MHz, CDCl₃) δ: 7.59 (d, J＝7.8 Hz, 1H), 7.42~7.39 (m, 1H), 7.16~7.09 (m, 3H), 7.00~6.91 (m, 4H), 6.68 (d, J＝8.4 Hz, 1H), 4.53 (s, 1H), 3.17~3.13 (m, 1H), 2.90~2.86 (m, 1H), 1.20 (s, 9H); ¹³C NMR (150 MHz, CDCl₃) δ: 202.6, 171.2, 163.1, 139.2, 138.5, 138.1, 135.4, 128.7, 127.5, 126.9, 124.0, 121.7, 120.7, 112.9, 95.4, 80.7, 59.8, 41.9, 27.7.

  3-氧代-5'-苯基-3H-螺[苯并呋喃-2, 4'-环戊烷]-2'-烯- 1'-羧酸乙酯(3v-α): 白色固体, 57 mg, 产率57%. mp 138~140 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.64~7.60 (m, 1H), 7.51~7.48 (m, 1H), 7.27~7.21 (m, 3H), 7.14~7.11 (m, 2H), 7.05 (t, J＝7.6 Hz, 1H), 6.99~6.96 (m, 2H), 4.48 (s, 1H), 4.17~4.03 (m, 2H), 3.26~3.21 (m, 1H), 2.83 (dd, J＝19.2 Hz, J＝2.8 Hz, 1H), 1.14 (t, J＝7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 198.7, 170.5, 163.4, 140.7, 137.9, 137.0, 134.9, 128.3, 128.2, 127.6, 124.5, 122.0, 121.2, 113.2, 96.8, 61.8, 60.5, 41.9, 14.0; HRMS (ESI) calcd for C₂₁H₁₇O₄ [M－H]^－ 333.12277, found 333.12201.

  3'-(叔丁基)-7-甲基-3-氧代-3H-螺[苯并呋喃-2, 2'-环戊烷]-1'-羧酸乙酯(4r-γ):白色固体, 48 mg, 产率74%. m.p. 89~93 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.54 (d, J＝7.8 Hz, 1H), 7.39 (d, J＝7.2 Hz, 1H), 6.98 (t, J＝7.2 Hz, 1H), 3.73~3.65 (m, 2H), 3.36 (t, J＝8.4 Hz, 1H), 2.46~2.35 (m, 2H), 2.26 (s, 3H), 2.14~2.00 (m, 3H), 0.79 (s, 9H), 0.57 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 203.4, 169.7, 137.7, 123.0, 122.4, 121.6, 121.3, 97.8, 60.4, 58.9, 55.2, 33.0, 29.1, 26.0, 24.2, 14.3, 13.1; HRMS (ESI) calcd for C₂₀H₂₇O₄ [M+H]⁺ 331.1904, found 331.1905.

  3'-(叔丁基)-5-甲氧基-3-氧代-3H-螺[苯并呋喃-2, 2'-环戊烷]-1'-羧酸乙酯(4s-γ):淡黄色液体, 55 mg, 产率80%. ¹H NMR (600 MHz, CDCl₃) δ: 7.22 (dd, J＝9.0 Hz, J＝3.0 Hz, 1H), 7.13 (d, J＝2.4 Hz, 1H), 6.98 (d, J＝9.0 Hz, 1H), 3.82 (s, 3H), 3.77~3.72 (m, 2H), 3.36 (t, J＝8.4 Hz, 1H), 2.44~2.34 (m, 2H), 2.11~1.99 (m, 3H), 0.79 (s, 9H), 0.66 (t, J＝7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 203.0, 169.7, 166.2, 154.9, 127.1, 123.0, 113.7, 104.3, 98.6, 60.4, 59.0, 55.9, 55.1, 32.9, 29.1, 25.9, 24.1, 13.4; HRMS (ESI) calcd for C₂₀H₂₇O₅ [M+H]⁺ 347.1853, found 347.1855.

  辅助材料(Supporting Information)  文中所有合成化合物的¹H NMR, ¹³C NMR谱图及质谱.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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  图 1  代表性螺环化合物

  Figure 1  Representative spiro compounds

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  图式 1  环化产物的还原

  Scheme 1  Reduction of the annulated compounds

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  图式 2  可能的反应机理

  Scheme 2  A possible mechanism

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  表 1  反应条件优化^a

  Table 1.  optimized conditions

  Entry	Cat.	Solvent	1a/2a	Yieldb/%	Time/h	3a-γ/3a-α
  1	PPh3	Toluene	1/2.0	82	18	2.3/1
  2	PPh3	Toluene	1/2.5	96	13	2.3/1
  3	PPh3	Toluene	1/3.0	96	13	2.3/1
  4	PBu3	Toluene	1/2.5	82	13	1/2.8
  5	PMe3	Toluene	1/2.5	18	24	1.1/1
  6	PCy3	Toluene	1/2.5	21	14	1/1
  7	Et3N	Toluene	1/2.5	n.d.	24
  8	AsPh3	Toluene	1/2.5	n.d.	24
  9c	PPh3	Toluene	1/2.5	65	14	1.7/1
  10d	PPh3	Toluene	1/2.5	59	14	1.7/1
  11	PPh3	CH3CN	1/2.5	12	24	5.3/1
  12	PPh3	CH3CH2OH	1/2.5	72	24	1.9/1
  13	PPh3	CH2Cl2	1/2.5	36	24	1.6/1
  14	PPh3	Tetrahydrofuran	1/2.5	Trace	24
  15e	PPh3	Toluene	1/2.5	57	24	2.4/1
  16 f	PPh3	Toluene	1/2.5	60	24	1.9/1
  17 g	PPh3	Toluene	1/2.5	47	24	1.7/1
  18h	PPh3	Toluene	1/2.5	40	24	2.0/1
  19h, i	PPh3	Toluene	1/2.5	65	38	1/1
  a All reactions were carried out by using 0.3 mmol of 1a, 2 mL of solvent; b Isolated yield; c 5 mol% PPh3 was used as catalyst; d 20 mol% PPh3 was used as catalyst; e The reaction was carried out at 25 ℃; f The reaction was carried out at 50 ℃; g The reaction was carried out at 110 ℃; h The reaction was carried out at air atmosphere; i After reacting for 24 h, additional 10 mol% PPh3 was added.

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  表 2  反应底物拓展^{a, b}

  Table 2.  Scope of substrates

  a All reactions were carried out by using 0.3 mmol of 1, 0.75 mmol of 2, 2 mL of toluene as solvent; b Isolated yield; c (E)-2-Benzylidenebenzofuran-3(2H)-one was used in the reaction.

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