N-Heterocyclic Carbene-Mediated Transformations of Silicon Reagents ⇑ ⇑ ⇑ Lin He , Hao Guo, Ying Wang, Guang-Fen Du , Bin Dai

Tetrahedron Letters 56 (2015) 972–980

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Tetrahedron Letters

journal homepage: www.elsevier.com/locate/tetlet

Digest Paper N-heterocyclic carbene-mediated transformations of silicon reagents ⇑ ⇑ ⇑ Lin He , Hao Guo, Ying Wang, Guang-Fen Du , Bin Dai

The Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Xinjiang Uygur Autonomous Region, 832000, China article info abstract

Article history: This review summarizes developments in N-heterocyclic carbene-mediated transformation of silicon Received 29 July 2014 reagents over the past decade. Several reactions of silicon reagents, including the sila-Stetter reaction, Revised 7 December 2014 1,2-addition, carbon–carbon and carbon–oxygen double bond reduction, polymerization, and other mis- Accepted 2 January 2015 cellaneous reactions, are discussed. The mechanisms of these reactions are also presented. Available online 12 January 2015 Ó 2015 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Keywords: N-heterocyclic carbenes Silicon reagents Stetter reaction 1,2-Addition Polymerization Reduction

Contents

Introduction...... 972 NHC-catalyzed sila-Stetter reaction of acylsilanes ...... 973 1,2-Nucleophilic addition reactions ...... 974 NHC-catalyzed cyanation and trifluoromethylation reactions ...... 974 NHC-catalyzed aldol reactions ...... 974 NHC-catalyzed transformations of silanes...... 975 NHC-catalyzed polymerization involving silicon reagents ...... 976 Other reactions ...... 976 Ring-opening reactions ...... 976 NHC-catalyzed MBH adducts ...... 977 NHC-catalyzed annulation ...... 978 NHC-catalyzed C–Si bond formation reaction ...... 978 Conclusion ...... 979 Acknowledgments ...... 979 References and notes ...... 979

Introduction been used as versatile organocatalysts to catalyze a series of organic reactions.3 More than half a century ago, Breslow proposed The past decade has witnessed tremendous growth in the a catalytic model for the thiazolium salt-catalyzed benzoin con- chemistry of N-heterocyclic carbenes (NHCs). NHCs have served densation reaction, and in situ-generated thiazolylidene (the as essential building blocks in synthetic chemistry1 and, owing to NHC) was assumed to be the reactive species in this reaction.4 In their excellent electronic properties, have been utilized as strong 1991, the ﬁrst stable NHC was isolated and characterized by Ardu- r-donor ligands for transition-metal catalysts.2 NHCs have also engo et al.5 These two ground-breaking works paved the way for the development of NHC catalysis. In 2004, the homoenolate reac- ⇑ Corresponding authors. Fax: +86 993 2057270. tion based on the NHC-catalyzed conjugate umpolung of enals was 6 E-mail address: [email protected] (L. He). independently developed by Glorious and Bode. In the same year, http://dx.doi.org/10.1016/j.tetlet.2015.01.034 0040-4039/Ó 2015 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). L. He et al. / Tetrahedron Letters 56 (2015) 972–980 973

R1 O O O O sila-Stetter 30 mol% 3a, DBU n C 1 + 2 3 2 3 reaction y R SiMe R R S tio a 3 R R c n re n u io a a Br d t c t 1a 4 e c t io 2 a io n N R re n HO(H2C)2 Et R1 M u NHC 3a n r k e o X a i a t a y l l d i c y a o N Y 3 o 1 z 2 t a i R i R O R o l P m r n O e a

m O + R2 R3 SNR R1R2R3SiX e 4 1 m n R SiMe3 o io O R u t i l p n if la e g r y n T in th g n R tio N OSiMe3 Form nyla An al tan on R1 nula S acti OH 1 S tion re S OH R N 7 5 R2 R3 R

Scheme 1. NHC-mediated transformation of silicon reagent. R'OH OH O S R1 R2 R3 redox transformation of a-functional aldehydes was indepen- 2 N 7 R'OSiMe R dently reported by Bode and Rovis. In 2008, Ye and co-workers 3 6 demonstrated the first example of NHC-catalyzed cycloaddition 8 of ketenes. Chi and co-workers recently demonstrated that NHCs Scheme 2. NHC-catalyzed sila-Stetter reaction. can be used to activate esters,9 which may be assumed to be another novel activation model of NHCs. Over the past decade, a large number of reactions promoted by NHCs have been investigated, and many excellent reviews have 2 been published in this research field. Besides the diverse reactions O R HOAc already mentioned, NHCs also exhibit highly catalytic activities 1 R SiMe3 1 3 10 R O R toward organic transformations of silicon reagents. A number 1a 1 R O 8 of reactions, such as the sila-Stetter reaction, 1,2-addition, C@C 20 mol% 3a, DBU O @ + R2 and C O bond hydrosilylation, polymerization, and other miscella- O THF, i-PrOH R2 R3 neous reactions, have been studied. The current review mainly 4 4 R NH2 R2 R3 1 3 focuses on the development of NHC-mediated transformations that R N R involve silicon reagents (Scheme 1). 2 R4 9 NHC-catalyzed sila-Stetter reaction of acylsilanes Scheme 3. One-pot synthesis of furans and pyrroles using NHC-catalyzed sila- Stetter reaction. The NHC-catalyzed conjugate addition of acyl anions and Michael acceptors, also called the Stetter reaction,11 is a convenient approach for the synthesis of 1,4-dicarbonyl compounds. However, acyl anions that are generated in situ through NHC-catalyzed R3 umpolung of aldehydes can also react with a secondary aldehyde 2 NO2 molecule; thus, benzoin condensation is unavoidable in this pro- R 4 R O 11 R cess. This problem can be overcome by using acylsilanes instead R3 NO2 of aldehydes as acyl anion precursors. Scheidt and co-workers R2 4 demonstrated that NHCs generated in situ from thiazolium salts OSiX3 Z R F O and the corresponding base can promote the sila-Stetter reaction R S O 12 12 R of acylsilanes and a,b-unsaturated ketones efficiently. In this N 1 OH process, highly nucleophilic NHC attack of acylsilanes facilitates R 10 carbonyl anion R 1,2-Brook rearrangement to produce the silylated acyl anion equiv- 13a alent 5; with the assistance of alcohol, 5 converts to 6, which O undergoes the following conjugate addition to produce a 1,4-dicar- 14 bonyl compound (Scheme 2). Using an NHC-catalyzed umpolung strategy with acylsilanes, Scheme 4. Transformations of o-silyl thiazolium carbinols. Scheidt and co-workers subsequently developed the one-flask syn- 13 thesis of polysubstituted furans and pyrroles. In situ-generated Bis-spiroacetals are an important unit that exists in various bio- 1,4-dicarbonyl compounds can be transformed into furans by the active marine phycotoxins.15 Landais recently reported that this addition of HOAc. Under the mediation of p-toluenesulfonic acid valuable skeleton can be prepared through an NHC-promoted (TsOH), 1,4-diketones can undergo Paal–Knorr reactions with sila-Stetter-ketalization cascade reaction.16 Under the catalysis of amines to produce pyrroles in one pot (Scheme 3). NHCs, aliphatic acylsilanes couple with vinyl ketones to produce The same group prepared and isolated stable O-silyl thiazolium 1,4-diketones, followed by deprotection of silyl ether and spiroace- carbinols 10, which can be used as precursors of acyl anions. With talization under acidic conditions to produce bis-spiroacetals 15 in the assistance of a fluoride source, thiazolium carbinols can moderate to good yields (Scheme 5). undergo the conjugate addition with nitroalkenes or o-quinone Fluoroalkene dipeptide isosteres (FADIs)17 are important build- 14 methides efficiently (Scheme 4). ing blocks in peptidomimetic drug research. Okata and co-workers 974 L. He et al. / Tetrahedron Letters 56 (2015) 972–980

O 15 mol% 3a O TBSO + SiMe 2Ph OTBS TBSO DBU, i-PrOH OTBS O THF, 75 O 1b 2' ഒ 4'

CSA 50mol% O O O CH3CN rt, 24h 15

Scheme 5. NHC-catalyzed synthesis of bis-spiroacetals.

F X F F 30mol% NHC R OEt + TMSCN Cat. TMSX CN R TBS R1 R2 1 2 DBU, EtOH NH O 23 R R Boc X=O,22a NH O 24a Boc 19, FADIs X=NP,22b X=O, 16 X=NP,24b

Scheme 8. NHC-catalyzed cyanosilylation reactions. EtOH NHC-catalyzed cyanation and trifluoromethylation reactions R R2 R 2 R1 1 N 1,2-Brook F N F F R Cyanohydrins and their silyl ethers are versatile synthons for R R3 rearrangement R 3 S S the synthesis of a variety of valuable building blocks, such as a- 20 NH O TBS NH OTBS hydroxy acids, a-amino alcohols, and 1,2-diols. The catalytic Boc Boc 17 18 addition of trimethylsilyl cyanide (TMSCN) to carbonyl compounds is one of the most common methods of preparing these types of Cl Cl Ph Ph molecules. tert-Amines, tert-phosphines, and other Lewis bases SN 21 NHC: SN can catalyze this nucleophilic addition efficiently. In 2006, Aoy- ama and co-workers successfully applied NHCs to catalyze cyano- 22 3b HO 3c silylation reactions of aldehydes, ketones, and imines; the last reaction is also known as the Strecker reaction. This investigation Scheme 6. NHC-mediated synthesis of FADIs using a,b-enoylsilanes. was shortly followed by a report by Song and co-workers,23 who utilized pre-isolated NHCs as catalysts and found that the NHC loading can be reduced to as low as 0.01 mol % without reducing yields. Maruoka and Suzuki demonstrated the highly similar SNMe O 24,25 O NHC-catalyzed cyanosilylation reaction of electrophiles. 30 mol% I H P Ph O P Ph Me Me N Suzuki et al. attempted the asymmetric version of this transforma- N 3d Ph + Ph 1 tion and obtained 22% ee.25 Zhang and Ying developed a stable 1 2 R R SiX3 R 26 R2 H DBU, CHCl , i-PrOH solid poly-NHC catalyst. This novel heterogeneous poly-NHC 3 O 1 20 21, 51-94% can catalyze cyanation of aldehydes and ketones in quantitative yields. More importantly, these poly-NHC particles can easily be Scheme 7. NHC-mediated addition of acylsilanes with imines. recovered and reused several times without decreasing their catalytic activity (Scheme 8). Two possible mechanisms were proposed for NHC-catalyzed recently reported a new protocol for the synthesis of FADIs via cyanation reactions. Song, Aoyama, and Kondo proposed that the NHC-catalyzed intramolecular redox reactions of c,c-difluoro- reaction proceeds via TMSCN attack by NHCs. Such a reaction 18 a,b-enoylsilanes. NHCs attack the carbonyl group of 16, followed results in the formation of a reactive pentavalent silicon interme- by Brook rearrangement to produce silylated acyl anion 17. The diate 25, facilitates the addition of a cyano group to aldehydes, bulky TBS group is assumed to be necessary to inhibit protonation and produces the desired product 26. Another possible pathway of 17 at the c-position, which leads to preferential formation of the for this reaction involves formation of zwitterionic species 28, fol- defluorinated species 18 and results in the final selective produc- lowed by transfer of the TMS group and nucleophilic attack of a tion of FADIs 19 (Scheme 6). cyano group to produce the desired product (Scheme 9). a-Amino ketones and their derivatives are versatile moieties in Song et al. utilized this activation strategy in the NHC-catalyzed both synthetic and medicinal chemistry. Similar as NHC-catalyzed trifluoromethylation of carbonyl compounds.27 Similar to cyanosi- sila-Stetter reaction, under the catalysis of NHCs, acylsilanes can be lylation, a key pentavalent silicon intermediate was assumed to be used as precursors to couple with N-phosphinoyl imines and pro- formed in this process, and only 0.5–1 mol % NHCs was necessary 19 duce a-amino ketones in high yields (Scheme 7). for this transformation (Scheme 10).

1,2-Nucleophilic addition reactions NHC-catalyzed aldol reactions

NHCs present excellent r-donating properties and show highly The Mukaiyama aldol reaction is one of the most important C–C catalytic activities for activating tetravalent silicon reagents. Based bond forming reactions.28 Both Lewis acids and Lewis bases can on this activation model, a variety of 1,2-addition reactions for dif- promote this reaction. Song reported that NHCs can be used as ferent silylated reagents and nucleophiles have been explored. strong carbon-centered Lewis bases to activate the Si–O bond in L. He et al. / Tetrahedron Letters 56 (2015) 972–980 975

Path A : R O O N N OSiMe3 OH N N Ar RCHO O Ar Ar O N Me SiCN Ar Mes N Mes 3 36 37a,anti 23 SiMe Me3Si CN R CN 3 27b, + (1 mol%) 25 26 + R Path B : RCHO O O 22c O Si OH O CN 37b,syn R H OTMS R H R CN Scheme 13. NHC-catalyzed vinylogous aldol reaction of 2-(trimethylsilyloxy)furan Ar N N Ar Ar Ar with aldehydes. N N product 28 27 OH Scheme 9. The mechanism of cyanosilylation reactions. 1) 27c (5 mol%),THF O (MeO)2POSiMe3 +RCHO R P 2) HCl, 0.5h MeO OMe 39 22c 39, yield up to 93% N N 1) 27c (0.5mol%) O OH 27a HO CF3 DMF,rt +TMSCF3 1 2 Me SiCH EWG + RCHO EWG R1 R2 R R 3 2 R 40 22c 2) HCl, rt 22a 29 30 41, 31-93% yield

EWG = CO2Et, COMe, CONMe2,CN Scheme 10. NHC-catalyzed triﬂuoromethylation of carbonyl compounds. R = aryl, heteroaryl, alkyl iPr iPr

N N OTMS OH R1 CO2Me iPr iPr OMe R2 33 31 NHC: 27c O 27a (0.5 mol%) or or Scheme 14. NHC-catalyzed phospho-Mukaiyama aldol reaction and silyl-Refor- R1 R2 OH O OTMS matsky reaction. 22a R1 2 Ph Ph R 32 34 O Scheme 11. NHC-catalyzed Mukaiyama aldol reaction. R H OTMS 22c 5mo%l27b, rt, THF R SnBu3 OTMS 43a, yield up to 100% OTMS or OMe O Ph OTMS Bu3Sn TMS 1 2 2 R O 1 R 1 R 42 R R R1 OTMS 1mol%27a 2 3 22a' 35 R R R2 5mo%l27b, 3 rt, THF Bu3Sn R Scheme 12. NHC-catalyzed silyl enol ether formation. 43b, yield up to 74%

Scheme 15. NHC-catalyzed stannylsilylation reaction of aldehydes. enoxysilanes and catalyze the Mukaiyama aldol reaction of aldehydes efficiently (Scheme 11).29 However, when ketones were used instead of aldehydes, an Based on this hypothesis, we successfully developed the NHC- unexpected silyl enol ether formation reaction occurred.30 In this catalyzed silyl-Reformatsky reaction of different silicon reagents, 33 reaction, NHCs functioned as a base to deprotonate ketones and which may be classified as a Mukaiyama aldol-type reaction. form an enolate intermediate, followed by silyl transfer to produce Parrain and co-workers recently demonstrated a novel NHC- 34 the new silyl enol ether 35 (Scheme 12). catalyzed stannylsilylation reaction of aldehydes (Scheme 15). Our group has reported the NHC-catalyzed vinylogous Mukaiy- The authors proposed that trialkylsilyl stannanes can be activated ama aldol reaction of 2-(trimethylsilyloxy)furan and aldehydes by NHCs through formation of a reactive pentavalent silicon inter- (Scheme 13).31 Based on the activation of Si–O bonds by NHCs, mediate, which can couple with aldehydes or enals to construct the silicon reagent smoothly couples with aldehydes to produce C–Sn bonds. The concept of formation of a pentavalent silicon 1 13 c-substituted butenolides with good anti-selectivity in high yields. intermediate was supported by H NMR and C NMR monitoring Using the same activation strategy, the NHC-catalyzed studies. phospho-Mukaiyama aldol reaction of dimethyl trimethylsilyl phosphite and aldehydes was also developed by our group NHC-catalyzed transformations of silanes (Scheme 14).32 This process is the first example of a NHC-mediated C–P bond forming reaction. Besides the Si–O bond, we proposed In 2009, Zhang and Ying reported the NHC-mediated reduction 35 that Si–C bonds could also be activated by NHCs through the for- of CO2 with silanes. The authors proposed an imidazolium car- mation of penta- or hexacoordinated NHC–silicon complexes. boxylate adduct as the reactive species 46; this adduct can attack 976 L. He et al. / Tetrahedron Letters 56 (2015) 972–980

27b (0.05-5 mol%) OH CO R SiOCH R SiOSiR 27c (2.5 mol%), neat 2 +3R3SiH 3 3 + 3 3 + R3 SiH R3 SiOCHR1R2 H 1 2 3 3 + 2 44 45 47 48 R R 55 59 60 H2O R SiOH + CH OH R SiH 3 3 27b Mes N N Mes 3 Scheme 20. NHC-catalyzed the dehydrogenative coupling of silanes and alcohols. 49 50 O O 46 initially assumed to be the primary mechanism for this reaction; however, a detailed mechanistic study revealed that NHCs act as Scheme 16. NHC-mediated reduction of CO2 with silanes. Brønsted bases to activate alcohols via deprotonation. Therefore, a general base catalysis mechanism was proposed. Based on the activation of alcohols by NHCs, Cui and co-workers O reported a novel protocol for synthesizing silyl ethers via NHC-cat- 1 R 1 38 + CO + PMHS 5mol%27c R NH 2 N H alyzed dehydrogenative coupling of silanes and alcohols. When 2 R R2 the stable pre-isolated 3,5-bis(2,6-diisopropylphenyl)imidazol-yli- 51 44 52 22d dene (IPr) was used for the reaction, high yields were obtained for most tested reactions (Scheme 20). Scheme 17. NHC-catalyzed formylation of amines. NHC-catalyzed polymerization involving silicon reagents

Waymouth, and co-workers,39 as well as Taton and co- O 1 OH R Ph 40 + Ph SiH Poly-NHC hydrolysis workers, recently independently developed NHC-catalyzed R1 R2 2 2 O Si H R1 R2 R2 Ph group-transfer polymerization (GTP), an important method for 22a 53 54 55 yield up to 99% polymerizing (meth)acrylic monomers based on repetition of N Mukaiyama–Michael reactions. Previous research shows that NHCs can initiate GTPs through activation of silyl ketene acetals. Two N mechanisms were proposed for this NHC-mediated GTP. The asso- 27d, Poly-NHC ciative mechanism suggested by Taton and Gnanou postulated that NHCs activate the reaction via formation of pentacoordinated sili- Scheme 18. Poly-NHC-catalyzed hydrosilylation reactions. con species. In 13C NMR and 29Si NMR experiments of a 1:1 molar mixture of NHC and MTS, no enolate-type species was detected. This result provides additional evidence supporting the associative

OH mechanism. Waymouth and Hedrick proposed a dissociative mech- OH 1) 57 (10 mol%) 2 2 R anism based on their kinetic studies. Here, imidazolium enolates 61 R R R1 were assumed to be the reactive species initiating GTP (Scheme 21). R1 Ph2SiH2, DMF,r.t., 6h 41 R 2) TBAF, r.t., 0.5h Taton and co-workers subsequently expanded this NHC-initi- 56 58,70-99% ated GTP to different types of monomers, and block copolymeriza- N N N tion of a variety of block copolymers was achieved through this organocatalytic methodology. 57a Waymouth and Hedrick utilized NHCs to promote ring-opening polymerization (ROP) of cyclic carbosiloxanes.42,44 1H NMR studies Scheme 19. NHC-mediated hydrosilylation of styryl alcohols and propargylic showed that NHCs act as bases to activate alcohols or silanols alcohols. through hydrogen bonding and initiate ROP. In a similar NHC-catalyzed ROP of cyclotetrasiloxane, Baceiredo and co-workers43 the silicon atom, initiate subsequent hydride transfer, and produce observed that the rate of polymerization is accelerated by increas- the ﬁnal methoxide products 50. After hydrolysis under basic con- ing the amount of NHCs (Scheme 22); here, bulky NHCs exhibit no ditions, methanol can be obtained in over 90% yield (Scheme 16). activity for ROP. Based on these ﬁndings, the authors proposed that Zhang and Ying’s research provided a promising methodology the reaction may proceed through a nucleophilic mechanism. for transforming and utilizing carbon dioxide. Very recently, Waymouth and co-workers found that, in the

Another NHC-catalyzed transformation of CO2 was developed absence of alcohol initiators, NHCs can catalyze ROP of carbosilox- 36 44 by Cantat and co-workers. Using CO2 and polymethylhydrosilox- anes to produce cyclic macromolecules (Scheme 23). As proposed ane (PMHS) as formylation reagents, formylation reactions of a by Baceiredo,43 nucleophilic attack of NHC on the silicon atom variety of N–H bonds were realized under the catalysis of NHCs would initiate this polymerization. (Scheme 17). In this study, the abundant and nontoxic characteris- Polycondensation is a versatile methodology for the synthesis of 43 tics of CO2 and PMHS made their large-scale recycling to be extre- silicon polymers. Baceiredo and co-workers successfully devel- mely attractive. oped the NHC-catalyzed polycondensation reaction of a,x-disila- Using diphenylsilane as a reductant, Zhang and Ying further nol oligomers (Scheme 24). Here, NHCs remained stable and 26 developed the hydrosilylation reaction of ketones and imine. active in the presence of H2O, thereby providing new opportunities Novel poly-NHC particles were prepared and utilized in this heter- for expanding the ﬁeld of NHC catalysis. ogeneous hydride transfer reaction, and the solid catalyst can be recycled and reused (Scheme 18). Other reactions NHCs can also catalyze the reduction of carbon–carbon double bonds and carbon-carbon triple bonds. Fensterbank, Lacôte, and Ring-opening reactions Goddard reported that NHCs promote hydrosilylation of styryl and propargylic alcohols with diphenylsilanes as the hydride Aziridines are versatile building blocks that can be transformed source (Scheme 19).37 Activation of Si–H bonds by NHCs was into a variety of nitrogen-containing scaffolds.45 Wu et al.46 L. He et al. / Tetrahedron Letters 56 (2015) 972–980 977

R N N R

MeO O SiMe3 N N R R O H,CH3 OMe R O H,CH OSiMe3 OSiMe3 3 R'O N Associative mechanism + 62 OMe N OMe R pentacoordinated siliconate O N N 31,MTS 27 61 + R R OMe SiMe3

H,CH3H,CH3 MeO OSiMe3 Dissociative mechanism R NNR + O MeO O OMe

Scheme 21. NHC-initiated group-transfer polymerization.

27 O Si Si Si R Si O H O ROH 64a 65

R N Si O O O O O Si O Si n N Si Si Si Si O OSi R 66 64b

N R'OH R N R N R N R OH H R'O O O O Si Si Si Si O O O R'O O Si Si Si Si 68

67 R' = alkyl, alkyl-(O-SiMe2)n-

Scheme 22. NHC-catalyzed ROP of cyclotetrasiloxane.

R Si Si O O 27 N Si Si O Si n Si Si R' O Si Si N n-1 R O R' Si 64a Si Si O 69 n-1 70

Scheme 23. NHC-mediated ROP of carbosiloxanes.

nH2O reported that NHCs can mediate ring-opening of aziridines with different tetravalent silicon reagents, such as TMSN3, TMSI, and nOHO Si Si O Si OH HO Si O Si O Si O H TMSCl, giving products with excellent anti-selectivity (Scheme 25). 8 8 n The pentavalent silicon intermediate was assumed to be the 71 72 reactive species in these ring-opening reactions. NN a:R=t-Bu R R b :R=c-Hex NHC-catalyzed MBH adducts 27 c:R=Mes

Scheme 24. Polycondensation of a,x-hydroxy oligodimethylsiloxane mediated by Morita–Baylis–Hillman (MBH) adducts are valuable synthons 47 NHCs. because of their high density of functional groups. However, 978 L. He et al. / Tetrahedron Letters 56 (2015) 972–980

NN R1 27b, 5mol% R1 NHR3 3 3 NR + Me3SiN3 R 2 THF, r.t. Me R N 2 2 R N3 Si R N3 73 74 Me R1 Me 75

Scheme 25. NHC-catalyzed ring-opening reaction of aziridines.

SiMe Ph 2 O catalytic O OH Brønsted base + 1 HO 1 R R R R H then 27c O R2 O O O 2 57b, 76 22c R + 20mol% CsF 77 Ar H R1 18-crow-6, n-Bu4NOAc O o O -18 C,THF Ar R R1 Ph H Ph N 85 13 N 86 R N R H N F R OSiMe Ph O PhMe Si 2 Et N 2 O R • 1 N N Et H R OSiZ3 Ph N 78 H n-Bu X 79 N Et R BF4 O 87 57b Et • H O OSiMe2Ph n Scheme 28. NHC-catalyzed formal [4+3] annulation. Et Ph 80 -Bu O

n-Bu 77a Ph H

Si-transfer 79 78 O O or O NN + B SiMe Ph Et Ph Ar Ar 2 O n-Bu 90, enantiomerically 91 O pure 81 1. activation O

Scheme 26. The mechanism of NHC-initiated addition of a-hydroxy-propargylsil- n SiMe Ph NN 2. addition n 2 anes to aldehydes. 88 Ar Ar , n = 1-4 93 O B SiMe2Ph O O O SiMe2Ph R G R G O CO Et 92 2 89, R = alky, OMe 94 OTMS RCHO R G = alky, aryl 22c R 83 Scheme 29. NHC-catalyzed silyl conjugate addition to unsaturated carbonyls. 27c (2 mol%) + + DCM, -20 oC Me3Si CO2Et OTMS in high yields. However, when ortho-substituted aromatic aldehydes were used in the reaction, alkynylation products were 82 R CO Et formed as the sole products 84 (Scheme 27). 84 2 NHC-catalyzed annulation Scheme 27. NHC-mediated addition of ethyl-3-(trimethylsilyl)propiolate with aldehydes. Using silyl-protected phenols as precursors of o-quinone methides, Scheidt and co-workers50 developed a novel dual Lewis base the synthesis of b-substituted MBH adducts remains challenging to activation strategy for asymmetric [3+4] annulation (Scheme 28). many researchers. Scheidt48 reported the NHC-initiated the The NHC-homoenolate intermediate coupled with the in situ-gen- addition of a-hydroxy-propargylsilanes to aldehydes, yielding erated Michael acceptor 13 to produce 2-benzoxopinones. These b-substituted MBH adducts with excellent stereoselectivity. The seven-membered lactones are the core unit of numerous bioactive NHC–aldehyde adduct was isolated and characterized by X-ray molecules. analysis for the ﬁrst time. These results provide strong evidence of the NHC-initiated mechanism, although a nucleophilic mecha- NHC-catalyzed C–Si bond formation reaction nism cannot be ruled out completely (Scheme 26). Our group49 recently reported the NHC-promoted synthesis of Hoveyda and O’Brien51 recently reported a C–Si bond formation b-substituted MBH adducts. Using IPr as a catalyst, 3-trimethylsilyl reaction through NHC-catalyzed silyl conjugate addition to a,b- propiolate coupled with two molecules of aldehydes to produce unsaturated carbonyls (Scheme 29). This research demonstrated b-acetylated MBH adducts 83 with excellent diastereoselectivity the highly catalytic activities of NHCs for Si–B bond activation, L. He et al. / Tetrahedron Letters 56 (2015) 972–980 979

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