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  2007年,Connon等^[12]报道了首例非酶催化剂参与的MBH加合物的动力学拆分反应,反应需在低温条件下进行,且选择性一般(S＝20). 2015年,本课题组^[13]利用酰基转移催化剂An-PIQ,对消旋α-烯基-β-羟基酯类化合物进行了动力学拆分研究,以优秀的选择性(＞99% ee,S高达108)得到了高光学纯的α-烯基-β-羟基酯类化合物(Scheme 1b). 在此基础上,我们希望利用该催化体系对消旋的β-碘代MBH加合物进行动力学拆分,以期获得具有重要合成应用价值的高光学纯β-碘代MBH加合物.

  另一方面,通过手性亲核催化剂催化的不对称酰化转移来获得高光学纯化合物的方法在近些年获得了广泛的关注^[7]. Vedejs^[8a,8b]及Fu等课题组^[8c～8e]分别开发了多种非酶手性膦和手性4-二甲基氨基吡啶(DMAP)类亲核酰基转移催化剂,并将其成功应用于各种二级醇的动力学拆分反应^[9],均取得了优秀的催化效果. Birman课题组^[10]开发的一类含大π电子体系的手性脒类酰基转移催化剂,如CF₃-PIP^[10a],Cl-PIQ^[10b],BTM^[10c]和HBT- M^[10d,10e]等,在催化芳香二级醇类底物的动力学拆分中,表现出优秀的对映选择性和底物普适性. 2010年,本课题组^[11]创造性地将平面手性DMAP类催化剂和手性脒类催化剂进行结合,合成了一类同时含有中心手性和平面手性的新型二氢咪唑类催化剂,该催化剂在芳基烷基甲醇类化合物的动力学拆分中表现出非常优异的对映选择性(S值最高可达1892) (Scheme 1a). 虽然二级醇的动力学拆分研究目前取得了快速的发展,但关于α-烯 基-β-羟基酯类(MBH加合物)二级醇的动力学拆分却进展缓慢,鲜有报道.

  α-烯基-β-羟基酯类化合物是一种常见的多官能团化手性砌块,被应用于多种重要光学纯天然产物和活性化合物的合成当中,如Trichodermone A,AOSA,(R)-Un- belactone等^{[1, 2]}. 而作为Morita-Baylis-Hillman (MBH)加合物重要的一类化合物,β-碘代MBH加合物因其β-位的碘原子可以进一步衍生,用途更为广泛. 光学纯的β-碘代MBH加合物可以作为关键中间体合成多种活性化合物^[3]. 例如,(-)-litsenolide A₁和(＋)-dihydromahu- benolide A均为来自海洋植物的活性天然产物,具有一定的抗肿瘤作用^[3g]. 5-episinuleptolide是一种来自淡紫灰链霉菌的活性二萜类化合物^[3h～3i],而(＋)-blastmy- cinon则是链霉菌产生的抗霉素的降解物^[3g].

  因此,手性β-碘代MBH加合物及其衍生物的合成受到越来越多化学家的关注. 目前最常用的策略是通过催化不对称合成的方法来获得此类化合物^[4]. 2001年,Li等^[5a]以N-氟酰基噁唑硼烷为催化剂,以甲基硅烷丙二烯酯和醛为底物,通过不对称Aldol反应,以70%的收率和高达98% ee合成了手性β-碘代MBH酮及酯. 2005年,该课题组^[5c]又以(R,R)-Salen AlCl为手性催化剂,碘化锂为添加剂,通过乙炔酸酯和醛合成了手性β-碘代MBH酯,但只获得中等对映选择性(ee值最高为65%). 2009年,Do小组^[5d]利用含有阳离子的手性噁唑硼烷类化合物为催化剂,实现了乙炔酸酯、醛和碘代三甲基硅烷三组分不对称偶联反应,以较高的收率和优秀的对映选择性获得了手性β-碘代MBH酯(Eq. 1),Z/E和ee值分别高达99:1和96%,但该反应催化剂用量较高,且需在较低的温度下进行,反应条件受限^[6].

  

  图图式 1 手性酰基转移催化剂参与的二级醇类化合物的动力学拆分

  Figure 图式 1. Kinetic resolution of secondary alcohols catalyzed by chiral acyl transfer catalysts

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  1    结果与讨论

  1.1    条件筛选

  我们以Z-构型的β-碘代MBH加合物1c为模型底物,异丙醚为溶剂,丙酸酐为酰化试剂,0 ℃氮气保护条件下进行条件筛选. 首先考察了不同催化剂对反应的影响,相对于催化剂Fc-PIP (S＝45)和Cl-PIQ (S＝42),含有大π取代基团的轴手性脒类催化剂An-PIQ (S＝70)和Np-PIQ(S＝68)表现良好(表 1,Entries 1,4). 因此,我们以An-PIQ为催化剂,对溶剂进行筛选,结果显示各种溶剂对反应选择性影响差别不大(S＝63,71,64) (表 1,Entries 2,5,7),异丙醚效果稍好. 而对酸酐的考察发现,以乙酸酐和异丁酸酐为酰化试剂时,反应选择性均明显下降(表 1,Entries 8,9),因此以丙酸酐为最佳酰化试剂. 继续考察碱对该反应的影响,结果显示有机碱三乙胺和N,N-二异丙基乙胺(S＝73,71)与无机碱碳酸钾 (S＝70)对反应选择性的影响类似(表 1,Entries 2,10,11),仍选择碳酸钾为最佳碱试剂. 最后对反应温度进行了考察,室温下该反应选择性降低(S＝47),而-20 ℃下反应选择性明显提高(S＝103),但是回收醇的ee值(42.2%)和转化率(30.3%)均大幅降低(表 1,Entries 12,13). 因此我们最终确定以An-PIQ为催化剂,异丙醚为溶剂,碳酸钾为碱,丙酸酐为酰化试剂以及反应温度为0 ℃为最优条件.

  表1 β-碘代MBH加合物动力学拆分反应的条件筛选^a Table1. Reaction condition screening for the kinetic resolution of β-iodo MBH adducts

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  Entry	Catalyst	Solvent	Anhydride	Base	Temp/℃	ee/%		CHPLCb/%	S c
  						1	2
  1	Fc-PIP	i-Pr2O	(EtCO)2O	K2CO3	0	63.1	91.9	40.7	45
  2	An-PIQ	i-Pr2O	(EtCO)2O	K2CO3	0	97.9	88.8	52.2	70
  3	Np-PIQ	i-Pr2O	(EtCO)2O	K2CO3	0	86.5	92.1	48.4	68
  4	Cl-PIQ	i-Pr2O	(EtCO)2O	K2CO3	0	64.5	91.1	41.5	42
  5	An-PIQ	CPME	(EtCO)2O	K2CO3	0	76.4	92.9	45.1	63
  6	An-PIQ	Tol	(EtCO)2O	K2CO3	0	87.3	92.2	48.6	71
  7	An-PIQ	MTBE	(EtCO)2O	K2CO3	0	88.8	91.1	49.4	64
  8	An-PIQ	i-Pr2O	(MeCO)2O	K2CO3	0	86.2	84.4	50.5	33
  9	An-PIQ	i-Pr2O	(i-PrCO)2O	K2CO3	0	93.3	71.1	56.8	20
  10	An-PIQ	i-Pr2O	(EtCO)2O	Et3N	0	95.5	90.1	51.5	73
  11	An-PIQ	i-Pr2O	(EtCO)2O	DIPEA	0	76.7	93.7	45.0	71
  12	An-PIQ	i-Pr2O	(EtCO)2O	K2CO3	-20	42.2	97.1	30.3	103
  13	An-PIQ	i-Pr2O	(EtCO)2O	K2CO3	25	80.4	90	47.2	47
  a Reaction conditions: 1c (0.2 mmol),anhydride (0.15 mmol),base (0.1 mmol),catalyst (0.01 mmol),solvent (2 mL). Absolute configuration of (R)-1c was determined according to the reference[14]. b Calculated from the ee values of the ester (S)-2c and unreacted alcohol (R)-1c.c See supporting information for the calculation.

  表1 β-碘代MBH加合物动力学拆分反应的条件筛选^a
  Table1. Reaction condition screening for the kinetic resolution of β-iodo MBH adducts

  1.2    底物扩展

  表2 An-PIQ催化的动力学拆分反应底物范围及普适性^a Table2. Scope and generality of An-PIQ catalyzed KR

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  Entry	R1	R2	1	T/h	ee/%		CHPLCb/%	Sc
  					1	2
  1	Me	Et	1c	4	97.9	88.8	52.2	70
  2	Et	Et	1d	4	99.6	90.0	52.5	117
  				6	99.9	90.1	52.6	143
  3	n-Pr	Et	1e	4	99.8	86.7	53.5	95
  4	n-Bu	Et	1f	4	90.1	78.1	53.6	25
  5	i-Pr	Et	1g	4	93.3	95.5	49.4	151
  				6	97.0	95.0	50.5	165
  6	i-Bu	Et	1h	4	98.8	87.9	52.9	78
  7	cHex	Et	1i	4	99.7	90.3	52.4	125
  				6	99.9	90.4	52.5	148
  8	Ph	Et	1j	4	14.4	7.5	65.8	1
  9	4-NO2C6H4	Et	1k	4	27.7	23.9	53.7	2
  10	Naphthyl	Et	1l	4	13.3	15.3	46.5	2
  11	CH3CCH2	Et	1m	4	63.1	64.3	49.5	9
  12	PhCH2CH2	Et	1n	4	99.6	79.3	55.7	52
  13	TBSOCH2CH2	Et	1o	4	94.0	90.6	50.9	72
  14d	2-ThiopCH2CH2	Et	1p	2	89.5	86.4	50.88	41
  15	PhCH2CH2	Me	1q	4	82.1	90.8	47.5	53
  16e	n-Bu	Et	1r	4	40.1	84.5	32.2	18
  a Reaction conditions: rac-1 (0.2 mmol),(EtCO)2O (0.15 mmol),K2CO3 (0.1 mmol),An-PIQ (0.01 mmol),i-Pr2O (2 mL). Absolute configuration of (R)-1c was determined according to the reference [14]. b Calculated from the ee values of the ester (S)-2c and unreacted alcohol (R)-1c.c See supporting information for the calculation. dReaction time was 2 hours. e 1r was E-isomer.

  表2 An-PIQ催化的动力学拆分反应底物范围及普适性^a
  Table2. Scope and generality of An-PIQ catalyzed KR

  接下来,继续考察α位为苯基取代的底物1j,结果显示,反应活性较差,且几乎没有选择性(表 2,Entry 8,S＝1). 我们试图通过吸电子诱导效应降低芳环电子云密度从而减弱底物芳基与酰化催化剂之间的π-π作用,以减小其与底物烯基的竞争,合成了R¹为吸电子取代基的底物1k和含有大π电子云的底物1l,但反应结果仍不理想(表 2,Entries 9,10,S＝2,2). 当R¹含有烯基时,反应选择性仍旧较差(S＝9) (表 2,Entry 11). R¹为苯乙基时,由于碳链增长,其反应选择性达到了与长链脂肪族取代底物类似的结果(表 2,Entry 12,S＝52). 而当R¹为羟基保护基和噻吩环时,反应均取得中等选择性(表 2,Entries 13,14,S＝72,41). 为考察底物中碘原子对反应的影响,设计合成了底物1q,在相同反应条件下,与文献报道的不含碘原子的3-羟基-2-烯基苯戊甲酯相比^[6],该底物回收醇ee值和S值均有明显提高(表 2,Entry 15,S＝53)(3-羟基-2-烯基苯戊甲酯回收醇ee值为73.2%,酯ee值为79.1%,转化率为47.7%,S值为20),说明碘原子的存在有利于提高反应的选择性.

  

  图2 推测的催化剂An-PIQ与底物1c相互作用的过渡态模型

  Figure 2. Possible transition state for catalyst An-PIQ interac- ting with 1

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  为探究具有不同双键构型的底物是否对其选择性产生影响,我们设计合成了E-构型的底物1r. 与其同分异构体1f相比,反应活性和选择性均明显下降(表 2,Entries 4,16),可能当底物为Z-构型时,碘原子能通过大原子半径,与酰化试剂的大π取代基形成电子诱导效应而有利于过渡态立体控制(图 2). 最后,我们对反应的实用性进行了系统的研究,对有实际应用价值的底物1o进行了放大量实验(Eq. 2),结果显示,回收醇(R)-1o的ee值仍可达93.9%.

  在获得上述最优条件后,我们考察了该反应的底物普适性(表 2). 首先对R¹基团进行考察,当R¹为直链脂肪族取代基时,随着碳链的增长反应选择性先提高后降低(S＝80,117,95,25) (表 2,Entries 1,4),当R¹为乙基时,反应4 h回收醇ee值可达99.6%,S值为117,延长反应时间至6 h,S值进一步提高至143(表 2,Entry 2). 当R¹为正丁基时,底物1f反应选择性大幅降(S＝25) (表 2,Entry 4). 当R¹为支链的异丁基时,与羟基α位没有支链取代基的底物1d相比,其选择性显著提升(S＝151) (表 2,Entries 2,5),反应6 h后S值进一步提高至165. 当R¹为异戊基时,与羟基β位没有支链取代基的底物1f 相比,其选择性同样明显提升(S＝78) (表 2,Entries 4,6). 以上结果表明,在底物羟基的α位适当增加空间位阻比在β位增加空间位阻更加利于提高反应选择性. 因此,当R¹为环己基时,其回收醇ee值高达99.9%,S值最高为148 (表 2,Entry 7).

  2    结论

  综上所述,我们以自主开发的手性酰基转移亲核试剂An-PIQ为催化剂,首次实现了β-碘代MBH加合物的高效非酶动力学拆分,其拆分选择性中等到优秀(S值最高达165),相应的回收醇ee值高达99.9 %. 该方法不仅解决了脂肪醛衍生的MBH加合物二级醇在动力学拆分中的低选择性问题,而且具有条件温和,较好的底物普适性等特点. 同时,对可用于活性天然产物合成的重要中间体(R)-1o也成功放大至克量级规模,从而进一步阐明该方法在有机合成中的潜在应用价值.

  3    实验部分

  3.1    仪器与试剂

  ¹H NMR (400 MHz)和¹³C NMR (100 MHz)采用Bruker AV400核磁共振仪测定,所用溶剂为CDCl₃,TMS为内标; HRMS (ESI)采用英国VG公司ZAB-ZSE型双聚焦高分辨质谱仪测定; 旋光采用Autopol IV/IV- T-Rudolph旋光仪测定. 实验所用试剂均为市售分析化试剂.

  3.2    实验方法

  (S,Z)-3-(4-硝基苯基)-3-丙酰氧基-2-碘代亚甲基丙酸乙酯(2k): 淡黄色油状液体,44.2 mg,产率51%. ¹H NMR (400 MHz,CDCl₃) δ: 8.23 (d,J＝2.0 Hz,1H),8.21 (d,J＝2.0 Hz,1H),7.55 (d,J＝2.0 Hz,1H),7.53 (d,J＝2.0 Hz,1H),7.39 (d,J＝1.3 Hz,1H),6.70 (d,J＝1.3 Hz,1H),4.22 (q,J＝7.1 Hz,2H),2.43 (q,J＝7.1 Hz,2H),1.25 (t,J＝7.1 Hz,3H),1.16 (t,J＝7.1 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 171.3,163.1,146.9,143.0,140.0,127.3,122.8,87.8,73.3,60.7,26.5,12.9,7.9. HRMS (ESI-TOF) calcd for C₁₅H₁₆IO₆NNa [M＋Na]^＋: 455.9920,found 455.9919. (S)-2k: [ α ]_D²⁵-17.5 (c 1.0,CHCl₃) (23.9% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝60/1,λ＝254 nm,retention time: t_S＝30.44 min,t_R＝46.63 min].

  (S,Z)-3-(2-萘基)-3-丙酰氧基-2-碘代亚甲基丙酸乙酯(2l): 淡黄色油状液体,39.4 mg,产率45%. ¹H NMR (400 MHz,CDCl₃) δ: 8.06 (d,J＝8.3 Hz,1H),7.90～7.82 (m,2H),7.55 (d,J＝8.2 Hz,1H),7.53～7.51 (m,1H),7.50～7.47 (m,1H),7.46～7.42 (m,2H),6.92 (d,J＝1.5 Hz,1H),4.30～4.16 (m,2H),2.40 (q,J＝7.5,2H),1.19 (t,J＝7.1 Hz,3H),1.14 (t,J＝7.5 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 171.6,164.1,141.4,132.8,131.3,129.6,128.5,127.8,125.7,124.9,124.8,124.2,122.5,87.2,71.4,60.5,26.6,12.9,8.0. HRMS (ESI-TOF) calcd for C₁₉H₁₉IO₄Na [M＋Na]^＋: 461.0026,found 461.0225. (S)-2l: [ α ]_D²⁵＋1.0 (c 1,0 CHCl₃) (15.3% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝60/1,λ＝254 nm,retention time: t_S＝13.49 min,t_R＝12.05 min].

  (S,Z)-2-碘代亚甲基-3-丙酰氧基-戊酸乙酯(2d): 无色油状液体,34.7 mg,产率51%. ¹H NMR (400 MHz,CDCl) δ: 7.06 (s,1H),5.55～5.45 (m,1H),4.31 (q,J＝7.1 Hz,2H),2.36 (q,J＝7.6 Hz,2H),1.86～1.66 (m,2H),1.35 (t,J＝7.1 Hz,3H),1.15 (t,J＝7.6 Hz,3H),0.91 (t,J＝7.1 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.1,164.3,142.3,84.0,74.6,60.4,26.60,25.9,13.1,8.5,8.1. HRMS (ESI-TOF) calcd for C₁₁H₁₇IO₄Na [M＋Na]^＋: 363.0069,found 363.0068. (S)-2d: [ α ]_D²⁵-14.6 (c 1.0,CHCl₃) (90.1% ee). The ee was determined by HPLC [Chiralpak IF-H,1 mL/min,V(hexane)/V(i-PrOH)＝150/1,λ＝254 nm,retention time: t_S＝7.21 min,t_R＝6.56 min].

  (S,Z)-2-碘代亚甲基-3-丙酰氧基-5-甲基己酸乙酯(2h): 淡黄色油状液体,38.3 mg,产率52%. ¹H NMR (400 MHz,CDCl₃) δ: 7.08 (d,J＝1.0 Hz,1H),5.63 (dt,J＝8.9,4.3 Hz,1H),4.30 (q,J＝7.1 Hz,2H),2.34 (q,J＝7.6 Hz,2H),1.70～1.64 (m,1H),1.64～1.59 (m,1H),1.57～1.48 (m,1H),1.35 (t,J＝7.1 Hz,3H),1.14 (t,J＝7.6 Hz,3H),0.94 (d,J＝1.6 Hz,3H),0.92 (d,J＝1.6 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.2,164.2,143.1,84.0,72.1,60.4,42.2,26.6,23.7,22.0,20.8,13.1,8.0. HRMS (ESI-TOF) calcd for C₁₃H₂₁IO₄Na [M＋Na]^＋: 391.0382,found 391.0380. (S)-2h: [ α ]_D²⁵＋45.7 (c 1.0,CHCl₃) (89.1% ee). The ee was determined by HPLC [Chiralpak IF-H,1 mL/min,V(hexane)/V(i-PrOH)＝100/1,λ＝254 nm,retention time: t_S＝7.16 min,t_R＝6.58 min].

  (S,Z)-3-环己基-2-碘代亚甲基-3-丙酰氧基丙酸乙酯(2i): 淡黄色油状液体,40.2 mg,产率51%. ¹H NMR (400 MHz,CDCl₃) δ: 6.94 (d,J＝0.8 Hz,1H),5.32 (d,J＝7.2 Hz,1H),4.28 (q,J＝7.1 Hz,2H),2.33 (q,J＝7.6 Hz,2H),1.72 (dd,J＝6.9,3.5 Hz,3H),1.66～1.59 (m,2H),1.33 (t,J＝7.1 Hz,3H),1.29～1.17 (m,2H),1.16～1.09 (m,5H),1.01～0.88 (m,2H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.2,164.5,142.0,84.1,77.8,60.4,39.7,28.0,27.2,26.6,25.1,24.9,24.7,13.1,8.1. HRMS (ESI-TOF) calcd for C₁₅H₂₃IO₄Na [M＋Na]^＋: 417.0539,found 417.0540. (S)-2i: [ α ]_D²⁵＋49.0 (c 1.0,CHCl₃) (90.3% ee). The ee was determined by HPLC [Chiralcel AS-H,1 mL/min,V(hexane)/V(i-PrOH)＝100/1,λ＝254 nm,retention time: t_S＝5.37 min,t_R＝7.26 min].

  (R,Z)-3-(4-硝基苯基)-3-羟基-2-碘代亚甲基丙酸乙酯(1k): 棕黄色油状液体,35.5 mg,产率47%. ¹H NMR (400 MHz,CDCl₃) δ: 8.22 (d,J＝2.0 Hz,1H),8.21 (d,J＝2.0 Hz,1H),7.55 (d,J＝2.1 Hz,1H),7.54 (d,J＝2.1 Hz,1H),7.44 (d,J＝1.0 Hz,1H),5.63 (s,1H),4.22 (q,J＝7.1 Hz,2H),3.26 (s,1H),1.26 (t,J＝7.1 Hz,3H). (R)-1k: [ α ]_D²⁵＋6.2 (c 1.0,CHCl₃) (47.7% ee). The ee was determined by HPLC [Chiralcel OD-H,1 mL/min,V(hexane)/ V(i-PrOH)＝100/5,λ＝254 nm,retention time: t_R＝36.96 min,t_S＝33.48 min].

  (R,Z)-3-羟基-2-碘代亚甲基-丁酸乙酯(1c): 淡黄色油状液体,25.4 mg,产率47%. ¹H NMR (400 MHz,CDCl₃) δ: 7.16 (d,J＝1.1 Hz,1H),4.61 (q,J＝6.2 Hz,1H),4.33 (q,J＝7.1 Hz,2H),2.49 (d,J＝5.8 Hz,1H),1.39 (d,J＝6.2 Hz,3H),1.36 (q,J＝7.1 Hz,3H). (R)-1c: [ α ]_D²⁵＋6.7 (c 1.0,CHCl₃) (97.9% ee). The ee was determined by HPLC [Chiralpak AS-H,1 mL/min,V(hexane)/V(i- PrOH)＝40/1,λ＝254 nm,retention time: t_R＝17.33 min,t_S＝16.23 min].

  (S,Z)-2-碘代亚甲基-3-丙酰氧基-4-甲基戊酸乙酯(2g): 无色油状液体,34.7 mg,产率49%. ¹H NMR (400 MHz,CDCl₃) δ: 6.96 (s,1H),5.31 (d,J＝6.8 Hz,1H),4.28 (q,J＝7.1 Hz,2H),2.34 (q,J＝7.3 Hz,2H),2.02 (d,J＝6.8 Hz,1H),1.32 (t,J＝7.1 Hz,3H),1.12 (t,J＝7.3 Hz,3H),0.90～0.87 (m,6H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.2,164.4,141.9,84.2,78.2,60.4,30.3,26.6,17.7,16.6,13.1,8.1. HRMS (ESI-TOF) calcd for C₁₂H₁₉IO₄Na [M＋Na]^＋: 377.0026,found 377.0225. (S)-2g: [ α ]_D²⁵-3.1 (c 1.0,CHCl₃) (95.5% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/1,λ＝254 nm,retention time: t_S＝5.49 min,t_R＝4.88 min].

  (R,Z)-3-(2-萘基)-3-羟基-2-碘代亚甲基丙酸乙酯(1l): 棕黄色油状液体,40.5 mg,产率53%. ¹H NMR (400 MHz,CDCl₃) δ: 8.01 (d,J＝8.1 Hz,1H),7.88 (dd,J＝7.6,1.6 Hz,1H),7.84 (d,J＝8.1 Hz,1H),7.61 (d,J＝7.1 Hz,1H),7.55 (dd,J＝7.1,1.6 Hz,1H),7.51 (dd,J＝9.1,1.8 Hz,1H),7.46 (d,J＝7.6 Hz,1H),7.06 (d,J＝1.6 Hz,1H),6.33 (d,J＝5.0 Hz,1H),4.23 (q,J＝7.1 Hz,2H),2.83 (d,J＝5.0 Hz,1H),1.20 (t,J＝7.1 Hz,3H). (R)-1l: [ α ]_D²⁵-8.6 (c 1.0,CHCl₃) (13.3% ee). The ee was determined by HPLC Chiralpak AD-H,1 mL/min,V(hexane)/V(i- PrOH)＝80/20,λ＝254 nm,retention time: t_R＝8.05 min,t_S＝9.42 min].

  (R,Z)-3-羟基-2-碘代亚甲基-5-(2-噻吩)-戊酸乙酯(1p): 无色油状液体,35.2 mg,产率48%. ¹H NMR (400 MHz,CDCl₃) δ: 7.14 (s,1H),7.13 (dd,J＝5.1,1.1 Hz,1H),6.92 (dd,J＝5.1,3.5 Hz,1H),6.80 (d,J＝2.9 Hz,1H),4.44 (dt,J＝6.3 Hz,1H),4.32 (q,J＝7.1 Hz,2H),2.96 (q,J＝7.1 Hz,2H),2.57 (d,J＝6.3 Hz,1H),2.04 - 1.96 (m,2H),1.36 (t,J＝7.1 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 165.2,145.1,142.8,125.8,123.5,122.3,84.1,73.0,60.6,36.7,24.8,13.1. HRMS (ESI-TOF) calcd for C₁₂H₁₅IO₃SNa [M＋Na]^＋: 388.9684,found 388.9685. (R)-1p: [ α ]_D²⁵＋0.3 (c 1.0,CHCl₃) (89.5% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝150/1,λ＝254 nm,retention time: t_R＝55.77 min,t_S＝46.10 min].

  辅助材料(Supporting Information) 产物1c～1r和2c～2r的核磁共振谱图和HPLC图谱. 这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

  (R,Z)-3-羟基-2-碘代亚甲基-5-苯基戊酸甲酯(1q): 无色油状液体,36 mg,产率52%. ¹H NMR (400 MHz,CDCl₃) δ: 7.32～7.30 (m,1H),7.27 (d,J＝1.8 Hz,1H),7.21 (d,J＝1.3 Hz,1H),7.19 (d,J＝1.7 Hz,1H),7.21～7.15 (m,1H),7.15 (d,J＝1.0 Hz,1H),4.40 (dt,J＝7.3,6.4 Hz,1H),3.83 (s,3H),2.77 (d,J＝7.3 Hz,1H),2.69 (dt,J＝13.8,8.0 Hz,2H),1.95 (dt,J＝8.0,6.4 Hz,2H); ¹³C NMR (100 MHz,CDCl₃) δ: 166.8,146.4,141.1,128.5,128.5,126.1,85.4,74.4,52.1,37.5,31.7. HRMS (ESI-TOF) calcd for C₁₃H₁₅IO₃Na [M＋Na]^＋: 368.9964,found 368.9965. (R)-1q: [ α ]_D²⁵-2.0 (c 1.0,CHCl₃) (81.2% ee). The ee was determined by HPLC [Chiralcel OD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/20,λ＝254 nm,retention time: t_R＝9.22 min,t_S＝6.18 min].

  (S,Z)-2-碘代亚甲基-3-丙酰氧基-丁酸乙酯(2c): 黄色油状液体,32.6 mg,产率50%. ¹H NMR (400 MHz,CDCl₃) δ: 7.15 (s,1H),5.67 (q,J＝6.5 Hz,1H),4.31 (q,J＝7.1 Hz,2H),2.34 (q,J＝7.6 Hz,2H),1.41 (d,J＝6.5 Hz,3H),1.35 (t,J＝7.1 Hz,3H),1.14 (t,J＝7.6 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.0,164.2,143.4,83.9,69.8,60.5,26.7,18.9,13.1,8.0. HRMS (ESI-TOF) calcd for C₁₀H₁₅IO₄Na [M＋Na]^＋: 348.9913,found 348.9914. (S)-2c: [ α ]_D²⁵-58.9 (c 1.0,CHCl₃) (88.8% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/1,λ＝254nm,retention time: t_S＝7.19 min,t_R＝6.67 min].

  在氮气保护条件下,将底物rac-1 (0.2 mmol)、An-PIQ (0.01 mmol)、碳酸钾(0.1 mmol)、2 mL干燥异丙醚依次加入到反应管中,于0 ℃条件下搅拌数分钟后,加入无水丙酸酐(0.15 mmol). 继续于0 ℃条件下搅拌,TLC监测反应进程,待反应完全后,滴加数滴无水甲醇淬灭反应. 薄层色谱板进行分离,得到(R)-1回收醇和(S)-2 酯. 分别将得到的回收醇和酯溶于异丙醇中,进行HPLC测试,并计算S值.

  (R,Z)-3-羟基-4-亚甲基-2-碘代亚甲基戊酸乙酯(1m): 淡黄色油状液体,29.6 mg,产率50%. ¹H NMR (400 MHz,CDCl₃) δ: 7.19 (d,J＝1.1 Hz,1H),5.08 (s,1H),4.99 (s,1H),4.88 (d,J＝6.1 Hz,1H),4.29 (q,J＝7.1 Hz,2H),2.60 (d,J＝6.1 Hz,1H),1.71 (s,3H),1.34 (t,J＝7.1 Hz,3H). (R)-1m: [ α ]_D²⁵-9.6 (c 1.0,CHCl₃) (63.1% ee). The ee was determined by HPLC [Chiralcel OJ-H,1 mL/min,V(hexane)/V(i-PrOH)＝100/5,λ＝254 nm,retention time: t_R＝11.65 min,t_S＝12.04 min].

  (S,E)-2-碘代亚甲基-3-丙酰氧基庚酸乙酯(2r): 无色油状液体,49.3 mg,产率67%. ¹H NMR (400 MHz,CDCl₃) δ: 7.91 (s,1H),5.69 (dd,J＝8.6,6.0 Hz,1H),4.22 (q,J＝7.1 Hz,2H),2.36 (q,J＝7.6 Hz,2H),2.09～1.78 (m,2H),1.47～1.36 (m,2H),1.34～1.37 (m,2H),1.30 (t,J＝7.1 Hz,3H),1.13 (t,J＝7.6 Hz,3H),0.91 (t,J＝7.1 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.8,161.4,140.4,97.4,74.3,60.3,31.0,26.7,26.4,21.4,13.1,12.9,8.0. HRMS (ESI-TOF) calcd for C₁₃H₂₁IO₄Na [M＋Na]^＋: 391.0382,found 391.0381. (S)-2r: [ α ]_D²⁵＋0.1 (c 1.0,CHCl₃) (84.5% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝60/1,λ＝254nm,retention time: t_S＝5.45 min,t_R＝4.85 min].

  (S,Z)-2-碘代亚甲基-5-苯基-3-丙酰氧基戊酸甲酯(2q): 无色油状液体,37.0 mg,产率46%. ¹H NMR (500 MHz,CDCl₃) δ: 7.31～7.24 (m,2H),7.21～7.12 (m,4H),5.59～5.55 (m,1H),3.81 (s,3H),2.71～2.57 (m,2H),2.33 (q,J＝7.6 Hz,2H),2.11～2.00 (m,2H),1.14 (t,J＝7.6 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 173.0,165.5,143.2,140.6,128.4,128.2,126.1,86.0,74.0,52.1,35.3,31.4,27.5,9.0. HRMS (ESI-TOF) calcd for C₁₆H₁₉IO₄Na [M＋Na]^＋: 425.0026,found 425.0227. (S)-2q: [ α ]_D²⁵-29.8 (c 1.0,CHCl₃) (90.8% ee). The ee was determined by HPLC [Chiralcel AD-H,1 mL/min,V(hexane)/V(i- PrOH)＝80/1,λ＝254 nm,retention time: t_S＝12.88 min,t_R＝11.18 min].

  (R,Z)-3-苯基-3-羟基-2-碘代亚甲基丙酸乙酯(1j): 淡黄色油状液体,31.2 mg,产率47%. ¹H NMR (400 MHz,CDCl₃) δ: 7.39～7.29 (m,5H),7.26 (d,J＝1.3 Hz,1H),5.54 (dd,J＝5.5,1.3 Hz,1H),4.19 (q,J＝7.1 Hz,2H),2.90 (d,J＝5.5 Hz,1H),1.22 (t,J＝7.1 Hz,3H). (R)-1j: [ α ]_D²⁵＋9.0 (c 1.0,CHCl₃) (14.4% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝40/1,λ＝254 nm,retention time: t_R＝32.77 min,t_S＝35.18 min].

  (R,Z)-3-羟基-2-碘代亚甲基-庚酸乙酯(1f): 无色油状液体,28.7 mg,产率46%. ¹H NMR (400 MHz,CDCl₃) δ: 7.08 (d,1H),4.39 (dt,J＝7.1,5.8 Hz,1H),4.32 (q,J＝7.1 Hz,2H),2.62 (d,J＝5.8 Hz,1H),1.61 (dt,J＝6.9,5.8 Hz,2H),1.39～1.33 (m,5H),1.31 (q,J＝7.1Hz,2H),0.90 (t,J＝6.9 Hz,3H). (R)-1f: [ α ]_D²⁵＋2.0 (c 1.0,CHCl₃) (90.1% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/1,λ＝254 nm,retention time: t_R＝20.23 min,t_S＝21.50 min].

  (S,Z)-2-碘代亚甲基-3-丙酰氧基-己酸乙酯(2e): 无色油状液体,36.8 mg,产率52%. ¹H NMR (400 MHz,CDCl₃) δ: 7.06 (d,J＝1.0 Hz,1H),5.57 (t,J＝6.6 Hz,1H),4.30 (q,J＝7.1 Hz,2H),2.34 (q,J＝7.6 Hz,2H),1.69 (q,J＝7.8 Hz,2H),1.38～1.33 (m,5H),1.14 (t,J＝7.6 Hz,3H),0.91 (t,J＝7.3 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 173.2,165.3,143.7,85.0,74.3,61.5,36.0,27.6,18.5,14.1,13.67,9.1. HRMS (ESI-TOF) calcd for C₁₂H₁₉IO₄Na [M＋Na]^＋: 377.0226,found 377.0227. (S)-2e: [ α ]_D²⁵＋39.7 (c 1.0,CHCl₃) (86.7% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i- PrOH)＝100/1,λ＝254 nm,retention time: t_S＝7.47 min,t_R＝6.82 min].

  (R,E)-3-羟基-2-碘代亚甲基庚酸乙酯(1r): 无色油状液体,20.0 mg,产率32%. ¹H NMR (400 MHz,CDCl₃) δ: 7.87 (s,1H),4.58 (dt,J＝11.3,8.6 Hz,1H),4.25 (q,J＝7.1 Hz,2H),3.44 (d,J＝11.3 Hz,1H),1.85～1.73 (m,1H),1.59～1.69 (m,1H),1.55～1.43 (m,2H),1.40～1.35 (m,2H),1.33 (t,J＝7.1 Hz,3H),0.92 (t,J＝7.1 Hz,3H). (R)-1r: [ α ]_D²⁵-0.1 (c 1.0,CHCl₃) (40.1% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝40/1,λ＝254 nm,retention time: t_R＝7.71 min,t_S＝8.42 min).

  (S,Z)-2-碘代亚甲基-3-丙酰氧基-庚酸乙酯(2f): 无色油状液体,39.0 mg,产率53%. ¹H NMR (400 MHz,CDCl₃) δ: 7.06 (d,J＝1.0 Hz,1H),5.55 (d,J＝7.6 Hz,1H),4.31 (q,J＝7.1 Hz,2H),2.35 (q,J＝7.5 Hz,2H),1.80～1.62 (m,2H),1.35 (t,J＝7.2 Hz,3H),1.33～1.25 (m,4H),1.15 (t,J＝7.6 Hz,3H),0.89 (t,J＝6.9 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.2,164.3,142.8,83.9,73.5,60.4,32.6,26.6,26.2,21.2,13.1,12.9,8.0. HRMS (ESI-TOF) calcd for C₁₃H₂₁IO₄Na [M＋Na]^＋: 391.0382,found 391.0381. (S)-2f: [ α ]_D²⁵-56.2 (c 1.0,CHCl₃) (78.1% ee). The ee was determined by HPLC [Chiralpak AS-H,1 mL/min,V(hexane)/V(i-PrOH)＝300/1,λ＝254 nm,retention time: t_S＝4.75 min,t_R＝4.97 min].

  (R,Z)-3-环己基-3-羟基-2-碘代亚甲基丙酸乙酯(1i): 淡黄色油状液体,31.1 mg,产率46%. ¹H NMR (400 MHz,CDCl₃) δ: 6.99 (d,J＝0.9 Hz,1H),4.32 (q,J＝7.1 Hz,2H),4.07 (d,J＝7.1 Hz,1H),1.93 (d,J＝12.6 Hz,1H),1.79～1.70 (m,2H),1.67～1.53 (m,2H),1.49 (dt,J＝6.9,3.5 Hz,1H),1.37 (t,J＝7.1 Hz,3H),1.30～1.07 (m,4H),1.01～0.91 (m,2H). (R)-1i: [ α ]_D²⁵＋6.4 (c 1.0,CHCl₃) (99.7% ee). The ee was determined by HPLC [Chiralpak AD-H ,1 mL/min,V(hexane)/V(i-PrOH)＝60/1,λ＝254 nm,retention time: t_R＝24.43 min,t_S＝21.33 min].

  (S,Z)-2-碘代亚甲基-3-丙酰氧基-5-(2-噻吩)-戊酸乙酯(2p): 无色油状液体,42.2 mg,产率50%. ¹H NMR (400 MHz,CDCl₃) δ: 7.26 (s,1H),7.12 (dd,J＝5.1,1.2 Hz,1H),7.11 (d,J＝1.0 Hz,1H),6.91 (dd,J＝5.1,3.4 Hz,1H),6.78 (dd,J＝3.4,1.1 Hz,1H),5.59 (dd,J＝6.6,5.1 Hz,1H),4.30 (q,J＝7.1 Hz,2H),2.88 (t,J＝7.6 Hz,2H),2.35 (q,J＝7.8 Hz,2H),2.16～2.08 (m,2H),1.34 (t,J＝7.1 Hz,3H),1.15 (t,J＝7.8 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.0,164.1,142.2,142.0,125.8,123.5,122.4,84.8,72.7 ,60.5,34.6,26.6,24.6,13.1,8.0. HRMS (ESI-TOF) calcd for C₁₅H₁₉IO₄SNa [M＋Na]^＋: 444.9946,found 444.9948. (S)-2p: [ α ]_D²⁵-29.5 (c 1.0,CHCl₃) (86.4% ee). The ee was determined by HPLC [Chiralcel AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝60/1,λ＝254 nm,retention time: t_S＝10.26 min,t_R＝9.08 min].

  (R,Z)-5-叔丁基二甲基硅氧基-3-羟基-2-碘代亚甲基戊酸乙酯(1o): 无色油状液体,39.8 mg,产率48%. ¹H NMR (400 MHz,CDCl₃) δ: 7.22 (s,1H),4.70 (dt,J＝7.9,3.6 Hz,1H),4.29 (q,J＝7.1 Hz,2H),4.16 (d,J＝4.3 Hz,1H),3.91～3.77 (m,2H),1.95 (ddt,J＝13.6,6.6,3.6 Hz,1H),1.75 (ddt,J＝11.1,7.2,3.6 Hz,1H),1.35 (t,J＝7.1 Hz,3H),0.90 (s,9H),0.08 (s,6H); ¹³C NMR (100 MHz,CDCl₃) δ: 166.2,146.0,84.4,74.2,61.9,61.3,37.0,25.8,18.1,14.2,-5.5,-5.6. HRMS (ESI-TOF) calcd for C₁₄H₂₇IO₄SiNa [M＋Na]^＋: 437.0621,found 437.0623. (S)-2o: [ α ]_D²⁵＋52.2 (c 1.0,CHCl₃) (94.0% ee). The ee was determined by HPLC [Chiralpak IA-H,1 mL/min,V(hexane)/V(i-PrOH)＝200/1,λ＝254 nm,retention time: t_R＝14.02 min,t_S＝16.05 min].

  (S,Z)-2-碘代亚甲基-5-苯基-3-丙酰氧基戊酸乙酯(2n): 淡黄色油状液体,43.3 mg,产率52%. ¹H NMR (400 MHz,CDCl₃) δ: 7.31～7.25 (m,2H),7.19 (d,J＝7.1 Hz,1H),7.17～7.12 (m,2H),7.08 (s,1H),5.65～5.50 (m,1H),4.29 (q,J＝7.1 Hz,2H),2.74～2.58 (m,2H),2.33 (q,J＝7.6 Hz,2H),2.16～1.96 (m,2H),1.32 (t,J＝7.1 Hz,3H),1.15 (t,J＝7.6 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.1,164.2,142.3,139.7,127.5,127.3,125.1,84.5,73.1,60.5,34.4,30.5,26.5,13.1. HRMS (ESI-TOF) calcd for C₁₇H₂₁IO₄Na [M＋Na]^＋: 439.0382,found 339.0381. (S)-2n: [ α ]_D²⁵-20.2 (c 1.0,CHCl₃) (79.3% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/1,λ＝254 nm,retention time: t_S＝11.79 min,t_R＝10.50 min].

  (S,Z)-5-叔丁基二甲基硅氧基-2-碘代亚甲基-3-丙酰氧基戊酸乙酯(2o): 无色油状液体,47.0 mg,产率50%. ¹H NMR (400 MHz,CDCl₃) δ: 7.07 (s,1H),5.69 (t,J＝5.2 Hz,1H),4.29 (q,J＝7.1 Hz,2H),3.63 (t,J＝5.7 Hz,2H),2.33 (q,J＝7.6 Hz,2H),2.05～1.83 (m,2H),1.34 (t,J＝7.1 Hz,3H),1.13 (t,J＝7.6 Hz,3H),0.88 (s,9H),0.02 (s,6H); ¹³C NMR (100 MHz,CDCl₃) δ: 172.6,163.9,142.8,84.4,70.2,60.9,57.3,34.0,27.3,25.1,17.2,13.1,8.1,-5.5,-5.6. HRMS (ESI-TOF) calcd for C₁₇H₃₁IO₅SiNa [M＋Na]^＋: 493.0083,found 493.0082. (S)-2o: [ α ]_D²⁵-54.3 (c 1.0,CHCl₃) (90.6% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝300/1,λ＝254 nm,retention time: t_S＝9.71 min,t_R＝9.03 min].

  (S,Z)-4-亚甲基-3-丙酰氧基-2-碘代亚甲基戊酸乙酯(2m): 无色油状液体,34.5 mg,产率49%. ¹H NMR (400 MHz,CDCl₃) δ: 7.17 (d,J＝0.6 Hz,1H),6.02 (s,1H),5.09 (s,1H),5.04 (s,1H),4.28 (q,J＝7.1 Hz,2H),2.39 (q,J＝7.6 Hz,2H),1.71 (s,3H),1.33 (t,J＝7.1 Hz,3H),1.16 (t,J＝7.6 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 171.6,164.0,140.3,139.1,114.1,85.5,75.3,60.5,26.6,17.4,13.1,8.0. HRMS (ESI-TOF) calcd for C₁₂H₁₇IO₄Na [M＋Na]^＋: 375.0069,found 375.0068. (S)-2m: [ α ]_D²⁵＋14.9 (c 1.0,CHCl₃) (64.3% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝40/1,λ＝254 nm,retention time: t_S＝6.21 min,t_R＝5.75 min].

  (R,Z)-3-羟基-2-碘代亚甲基-己酸乙酯(1e): 淡黄色油状液体,27.4 mg,产率46%. ¹H NMR (400 MHz,CDCl₃) δ: 7.10 (s,1H),4.40 (q,J＝6.3 Hz,1H),4.33 (q,J＝7.1 Hz,2H),2.43 (d,J＝6.3 Hz,1H),1.60 (dd,J＝8.1,6.3 Hz,2H),1.53～1.32 (m,5H),0.93 (t,J＝7.1 Hz,3H). (R)-1e: [ α ]_D²⁵＋1.7 (c 0.01,CHCl₃) (99.8% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/1,λ＝254 nm,retention time: t_R＝29.88 min,t _S＝32.15 min].

  (R,Z)-3-羟基-2-碘代亚甲基-5-甲基己酸乙酯(1h): 淡黄色油状液体,28.7 mg,产率46%. ¹H NMR (400 MHz,CDCl₃) δ: 7.13 (d,J＝1.0 Hz,1H),4.47 (d,J＝8.6 Hz,1H),4.40～4.22 (m,2H),2.35 (br,1H),1.85～1.71 (m,1H),1.58～1.50 (m,1H),1.46～1.40 (m,1H),1.38 (t,J＝7.1 Hz,3H),0.93 (dd,J＝6.6,1.5 Hz,6H); ¹³C NMR (100 MHz,CDCl₃) δ: 166.4,147.0,84.4,73.5,65,45.3,24.7,23.2,21.8,14.2. HRMS (ESI-TOF) calcd for C₁₀H₁₇IO₃Na [M＋Na]^＋: 355.0120,found 355.0121. (R)-1h: [ α ]_D²⁵-4.9 (c 1.0,CHCl₃) (98.8% ee). The ee was determined by HPLC [Chiralcel AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝60/1,λ＝254 nm,retention time: t_R＝24.08 min,t_S＝21.45 min].

  (R,Z)-3-羟基-2-碘代亚甲基-戊酸乙酯(1d): 黄色油状液体,26.1 mg,产率46%. ¹H NMR (400 MHz,CDCl₃) δ: 7.09 (d,J＝1.1 Hz,1H),4.32 (q,J＝7.1 Hz,2H),2.45 (d,J＝6.3 Hz,1H),1.69 (d,J＝6.3 Hz,1H),1.66～1.58 (m,2H),1.38 (t,J＝7.1 Hz,3H),0.95 (t,J＝7.1 Hz,3H). (R)-1d: [ α ]_D²⁵-2.4 (c 0.01,CHCl₃) (99.6% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/1,λ＝254 nm,retention time: t_R＝24.95 min,t_S＝26.24 min].

  (R,Z)-3-羟基-2-碘代亚甲基-5-苯基戊酸乙酯(1n): 黄色油状液体,32.4 mg,产率45%. ¹H NMR (400 MHz,CDCl₃) δ: 7.30 (d,J＝8.0 Hz,2H),7.22～7.16 (m,3H),7.12 (s,1H),4.40 (q,J＝6.6 Hz,1H),4.31 (q,J＝7.1 Hz,2H),2.84～2.64 (m,2H),2.44 (d,J＝6.6 Hz,1H),2.01～1.91 (m,2H),1.36 (t,J＝7.1 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 166.3,146.4,141.1,128.5,128.5,126.0,84.9,74.4,61.6,37.5,31.7,14.2. HRMS (ESI-TOF) calcd for C₁₄H₁₇IO₃Na [M＋Na]^＋: 383.0120,found 383.0121. (R)-1n: [ α ]_D²⁵-4.8 (c 1.0,CHCl₃) (99.6% ee). The ee was determined by HPLC [Chiralcel OD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/20,λ＝254 nm,retention time: t_R＝5.34 min,t_S＝7.86 min].

  (S,Z)-3-苯基-3-丙酰氧基-2-碘代亚甲基丙酸乙酯(2j): 无色油状液体,39.6 mg,产率51%. ¹H NMR (400 MHz,CDCl₃) δ: 7.38～7.29 (m,5H),7.13 (d,J＝1.5 Hz,1H),6.65 (d,J＝1.5 Hz,1H),4.21 (q,J＝7.1 Hz,2H),2.38 (q,J＝7.6 Hz,2H),1.23 (t,J＝7.1 Hz,3H),1.13 (t,J＝7.6 Hz,3H); ¹³C NMR (100 MHz,CDCl₃) δ: 171.5,163.7,141.6,135.7,127.7,127.6,126.5,86.0,74.3,60.4,26.6,12.9,7.9. HRMS (ESI-TOF) calcd for C₁₅H₁₇IO₄Na [M＋Na]^＋: 411.0069,found 411.0067. (S)-2j: [ α ]_D²⁵＋13.1 (c 1.0,CHCl₃) (7.5% ee). The ee was determined by HPLC [Chiralpak AD-H,1 mL/min,V(hexane)/V(i-PrOH)＝80/1,λ＝254 nm,retention time: t_S＝14.43 min,t_R＝15.05 min].

  (R,Z)-3-羟基-2-碘代亚甲基-4-甲基戊酸乙酯(1g). 无色油状液体,29.2 mg,产率49%. ¹H NMR (400 MHz,CDCl₃) δ: 6.95 (d,J＝1.0 Hz,1H),4.25 (q,J＝7.1 Hz,2H),4.04～3.98 (m,1H),2.51～2.44 (m,1H),1.77 (brs,1H),1.30 (t,J＝7.1 Hz,3H),0.89 (d,J＝6.7 Hz,3H),0.83 (d,J＝6.7 Hz,3H). (R)-1g: [ α ]_D²⁵＋0.3 (c 1.0,CHCl₃) (93.3% ee). The ee was determined by HPLC [Chiralcel OD-H,1 mL/min,V(hexane)/V(i-PrOH)＝60/1,λ＝254 nm,retention time: t_R＝12.10 min,t_S＝13.36 min].

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      For a review on (Z)-β-halo MBH synthesis, see:(a) Li, G.; Hook, J.; Wei, H.-X. In Recent Research Developments in Organic & Bioorganic Chemistry, Transworld Research Network, Kerala, India, 2001, Vol. 4, 49. (b) Kataoka, T.; Banno, Y.; Watanabe, S.; Iwamura, T.; Shimizu, H. Tetrahedron Lett. 1997, 38, 1809. (c) Watanabe, S.; Yamamoto, K.; Itagaki, Y.; Kataoka, T. J. Chem. Soc., Perkin Trans. 11999, 2053. (d) Li, G.; Wei, H.-X.; Caputo, T. D. Tetrahedron Lett. 2000, 41, 1. (e) Li, G.; Gao, J.; Wei, H.-X.; Enright, M. Org. Lett. 2000, 2, 617. (f) Timmons, C.; Kattuboina, A.; Banerjee, S.; Li, G. Tetrahedron Lett. 2006, 62, 7151.

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  图式 1  手性酰基转移催化剂参与的二级醇类化合物的动力学拆分

  Scheme 1  Kinetic resolution of secondary alcohols catalyzed by chiral acyl transfer catalysts

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  图 2  推测的催化剂An-PIQ与底物1c相互作用的过渡态模型

  Figure 2  Possible transition state for catalyst An-PIQ interac- ting with 1

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  表 1  β-碘代MBH加合物动力学拆分反应的条件筛选^a

  Table 1.  Reaction condition screening for the kinetic resolution of β-iodo MBH adducts

  Entry	Catalyst	Solvent	Anhydride	Base	Temp/℃	ee/%		CHPLCb/%	S c
  						1	2
  1	Fc-PIP	i-Pr2O	(EtCO)2O	K2CO3	0	63.1	91.9	40.7	45
  2	An-PIQ	i-Pr2O	(EtCO)2O	K2CO3	0	97.9	88.8	52.2	70
  3	Np-PIQ	i-Pr2O	(EtCO)2O	K2CO3	0	86.5	92.1	48.4	68
  4	Cl-PIQ	i-Pr2O	(EtCO)2O	K2CO3	0	64.5	91.1	41.5	42
  5	An-PIQ	CPME	(EtCO)2O	K2CO3	0	76.4	92.9	45.1	63
  6	An-PIQ	Tol	(EtCO)2O	K2CO3	0	87.3	92.2	48.6	71
  7	An-PIQ	MTBE	(EtCO)2O	K2CO3	0	88.8	91.1	49.4	64
  8	An-PIQ	i-Pr2O	(MeCO)2O	K2CO3	0	86.2	84.4	50.5	33
  9	An-PIQ	i-Pr2O	(i-PrCO)2O	K2CO3	0	93.3	71.1	56.8	20
  10	An-PIQ	i-Pr2O	(EtCO)2O	Et3N	0	95.5	90.1	51.5	73
  11	An-PIQ	i-Pr2O	(EtCO)2O	DIPEA	0	76.7	93.7	45.0	71
  12	An-PIQ	i-Pr2O	(EtCO)2O	K2CO3	-20	42.2	97.1	30.3	103
  13	An-PIQ	i-Pr2O	(EtCO)2O	K2CO3	25	80.4	90	47.2	47
  a Reaction conditions: 1c (0.2 mmol),anhydride (0.15 mmol),base (0.1 mmol),catalyst (0.01 mmol),solvent (2 mL). Absolute configuration of (R)-1c was determined according to the reference[14]. b Calculated from the ee values of the ester (S)-2c and unreacted alcohol (R)-1c.c See supporting information for the calculation.

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  表 2  An-PIQ催化的动力学拆分反应底物范围及普适性^a

  Table 2.  Scope and generality of An-PIQ catalyzed KR

  Entry	R1	R2	1	T/h	ee/%		CHPLCb/%	Sc
  					1	2
  1	Me	Et	1c	4	97.9	88.8	52.2	70
  2	Et	Et	1d	4	99.6	90.0	52.5	117
  				6	99.9	90.1	52.6	143
  3	n-Pr	Et	1e	4	99.8	86.7	53.5	95
  4	n-Bu	Et	1f	4	90.1	78.1	53.6	25
  5	i-Pr	Et	1g	4	93.3	95.5	49.4	151
  				6	97.0	95.0	50.5	165
  6	i-Bu	Et	1h	4	98.8	87.9	52.9	78
  7	cHex	Et	1i	4	99.7	90.3	52.4	125
  				6	99.9	90.4	52.5	148
  8	Ph	Et	1j	4	14.4	7.5	65.8	1
  9	4-NO2C6H4	Et	1k	4	27.7	23.9	53.7	2
  10	Naphthyl	Et	1l	4	13.3	15.3	46.5	2
  11	CH3CCH2	Et	1m	4	63.1	64.3	49.5	9
  12	PhCH2CH2	Et	1n	4	99.6	79.3	55.7	52
  13	TBSOCH2CH2	Et	1o	4	94.0	90.6	50.9	72
  14d	2-ThiopCH2CH2	Et	1p	2	89.5	86.4	50.88	41
  15	PhCH2CH2	Me	1q	4	82.1	90.8	47.5	53
  16e	n-Bu	Et	1r	4	40.1	84.5	32.2	18
  a Reaction conditions: rac-1 (0.2 mmol),(EtCO)2O (0.15 mmol),K2CO3 (0.1 mmol),An-PIQ (0.01 mmol),i-Pr2O (2 mL). Absolute configuration of (R)-1c was determined according to the reference [14]. b Calculated from the ee values of the ester (S)-2c and unreacted alcohol (R)-1c.c See supporting information for the calculation. dReaction time was 2 hours. e 1r was E-isomer.

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