TiCl4-Mediated Baylis–Hillman and aldol reactions without the direct use of a Lewis base

Li, Guigen; Wei, Han‐Xun; Gao, Jun; Caputo, Thomas D.

doi:10.1016/s0040-4039(99)01992-9

Cited by 127 publications

(28 citation statements)

References 14 publications

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“…In contrast, sulfides proved effective: treatment of a solution of pyrrolidine 1 and methyl vinyl ketone (MVK) with BF 3 ⋅OEt 2 and SMe 2 ,10a followed by treatment of the resultant crude mixture with DBU, resulted in the isolation of the MBH‐type adduct 2 a in 30 % yield. Other Lewis acid/Lewis base combinations were then investigated, namely TiCl 4 ,10c, 14 TiCl 4 /SMe 2 ,10b, 15 Et 2 Al‐I,16 and TMSOTf/SMe 2 7f,g. The latter combination was found to be optimum and provided adducts 2 a – m ; in good to excellent yield (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Reactions of Iminium Ions with Michael Acceptors through a Morita–Baylis–Hillman‐Type Reaction: Enantiocontrol and Applications in Synthesis

2007

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a-Functionalization of alkenes activated by electron-withdrawing groups (EWGs) encompass an important CÀC bondforming strategy in organic synthesis, and can be realized in one of three ways: a) metal-catalyzed functionalization of ahalogeno [1] or a-metallo substrates; [2] b) a vinylogous enolization, a-alkylation, and isomerization sequence; [3] or c) nucleophilic catalysis: the Rauhut-Currier and MoritaBaylis-Hillman (MBH) reactions.[4] The MBH transformation (Scheme 1), [5] which is traditionally effected by catalytic amounts of a tertiary amine or phosphine and uses an aldehyde as the terminal electrophile, has become more recently a powerful synthetic tool with the increased scope in Michael acceptors (for example, vinyl sulfones [6a] and acrylamides [6] ) and electrophiles (for example, halides, [7a,b] epoxides, [7c] allyl carbonates, [7d] acetals, [7e-h] and aryl cation equivalents [7i] ). A class of electrophile that has received little attention is N-acyl iminium ions [8] which would lead to biologically important and highly functionalized b'-amidoa,b-unsaturated carbonyl compounds.[9] Herein, we describe our success in employing this class of substrates and also in rendering the reaction asymmetric.Initial investigations focused on the pyrrolidine 1 (PG = Cbz, m = 1; Scheme 1) and reaction conditions in which a combination of a Lewis acid (to form the iminium ion electrophile) and a weak Lewis base (to form the enolate nucleophile) were used.[10] The standard Lewis bases for the MBH reaction (phosphines and amines) were ineffective with BF 3 ·OEt 2 : use of PPh 3 resulted in a stable phosphine-iminium ion adduct [11] presumably because of the poor leaving group ability of the phosphine, [12] and pyridine caused dimerization of the pyrrolidine presumably through base-promoted enamine formation and subsequent attack on a second iminium ion.[13] In contrast, sulfides proved effective: treatment of a solution of pyrrolidine 1 and methyl vinyl ketone (MVK) with BF 3 ·OEt 2 and SMe 2 , [10a] followed by treatment of the resultant crude mixture with DBU, resulted in the isolation of the MBH-type adduct 2 a in 30 % yield. Other Lewis acid/Lewis base combinations were then investigated, namely TiCl 4 , [10c, 14]

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Section: Methodsmentioning

confidence: 99%

Reactions of Iminium Ions with Michael Acceptors through a Morita–Baylis–Hillman‐Type Reaction: Enantiocontrol and Applications in Synthesis

2007

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“…]undec-7-ene (DBU) [5] and trimethylamine [6] are frequently used in these reactions as catalysts. In addition, Lewis acid-accelerated reactions using TiCl 4 [7] and BF 3 . [8] were also reported.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Poly(ethyleneglycol)-400 Ionic Liquid and Its Application in Morita–Baylis–Hillman Reaction

Zhao

Zhang

Duan

et al. 2011

Synthetic Communications

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“…8 (8) Lithium phenylselenide (PhSeLi) induced Baylis-Hillman reaction was applied successively to α,β-unsaturated lactone system. 9 In summary, for the BaylisHillman reaction of cycloalkenone derivatives, the combination of Lewis acid and Lewis base system 2,3,6 seemed the only choice except for the reactive formaldehyde.…”

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confidence: 99%

The Most Simple and Convenient Synthesis of the Baylis-Hillman Adducts of Cycloalkenones:Use of DMAP in Aqueous THF

Lee¹,

Gong²,

Kim³

2002

Bulletin of the Korean Chemical Society

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The Baylis-Hillman reaction, the coupling of aldehydes and activated vinyl compounds, is one of the most important carbon-carbon bond-forming reaction in organic synthesis. 1 The drawback to this methodology is its slow reaction rate, and many research groups have examined a variety of methods to accelerate the reaction. Among the activated alkenes cycloalkenones are famous.1b Under the normal reaction conditions using DABCO (1,4-diazabicyclo[2.2.2]-octane) no reaction was observed.Recently, various methods for the synthesis of the BaylisHillman adducts of cycloalkenones have been developed with certain limitations. (1) The combination of 2,6-diphenyl-4H-chalcogenopyran-4-ones (or -4-thions) and TiCl 4 in methylene chloride 2a and related methods were developed for the reactive p-nitrobenzaldehyde and 2-cyclohexen-1-one or 2-cyclopenten-1-one.2 (2) The combination of lithium perchlorate (LiClO 4 ) and DABCO in ether could be used for the Baylis-Hillman reaction of benzaldehyde and 2-cyclohexen-1-one.3 (3) The use of Et 2 AlI in CH 2 Cl 2 for the reaction of enone isolevoglucosenone and C-β-D-galactopyranosylformaldehyde furnished the corresponding BaylisHillman adduct.4 (4) 4-(Dimethylamino)pyridine (DMAP)-catalyzed hydroxymethylation of 2-cyclohexenones with formaldehyde was carried out effectively in aqueous medium. 5(5) Tributylphosphine combined with 1,1'-bi-2-naphthol was used effectively for cycloalkenone system. 6 (6) Lewis base effects including DMAP, tributylphosphine and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in the Baylis-Hillman reaction of 2-cyclohexen-1-one and arylaldehyde N-tosylimines were examined. 7 (7) Recently, it was known that TiCl4 without the use of Lewis base could be applied to highly reactive aldehydes.8 (8) Lithium phenylselenide (PhSeLi) induced Baylis-Hillman reaction was applied successively to α,β-unsaturated lactone system. 9 In summary, for the BaylisHillman reaction of cycloalkenone derivatives, the combination of Lewis acid and Lewis base system 2,3,6 seemed the only choice except for the reactive formaldehyde.5 However, most of the reported methods was limited to reactive aldehydes with low to moderate yields of products.In the course of our program for the synthesis of quinoline derivatives via SN2'-SNAr-elimination strategy, 10 we would like to extend the scope to the cycloalkenone derivatives. Thus, we needed the Baylis-Hillman adducts of 2-cyclohexen-1-one and various arylaldehydes. The use of DMAP, DBU, PBu3 or DABCO as a base catalyst did not give the desired products in THF or CH 2 Cl 2 . The use of expensive 2-cyclohexen-1-one as solvent is not clever. The use of known acid-base combination methods is not conveniently accessible to us. Thus, we intended to search for the simple conditions for the reaction. Among the examined conditions, the use of DMAP (0.2 equiv) in aqueous THF (1 : 1) suffice the formation of the desired Baylis-Hillman adducts in reasonable yields.11 As shown in Scheme 1 and in Table 1, we examined 2-cyclohexen-1-one (2a) and 2-cyclopenten-1-...

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TiCl4-Mediated Baylis–Hillman and aldol reactions without the direct use of a Lewis base

Cited by 127 publications

References 14 publications

Reactions of Iminium Ions with Michael Acceptors through a Morita–Baylis–Hillman‐Type Reaction: Enantiocontrol and Applications in Synthesis

Reactions of Iminium Ions with Michael Acceptors through a Morita–Baylis–Hillman‐Type Reaction: Enantiocontrol and Applications in Synthesis

Synthesis of Novel Poly(ethyleneglycol)-400 Ionic Liquid and Its Application in Morita–Baylis–Hillman Reaction

The Most Simple and Convenient Synthesis of the Baylis-Hillman Adducts of Cycloalkenones:Use of DMAP in Aqueous THF

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