Titanium(IV) Chloride and the Amine-Promoted Baylis−Hillman Reaction

Shi, Min; Jiang, Jian-Kang; Feng, Yingbin

doi:10.1021/ol000046x

Cited by 90 publications

(21 citation statements)

References 15 publications

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“…Among those Lewis acids examined, TiCl 4 has been successfully used to promote the Baylis-Hillman reaction in the presence of Lewis base catalysts [ 9 , 11 , 12 ]. During our own investigations of the Baylis-Hillman process we found that many amines are very effective Lewis bases in this interesting reaction and the reaction products differ considerably from those reported so far [ 13 ]. Herein we wish to report the full details of the titanium (IV) chloride, boron (III) chloride or zirconium (IV) chloride and amine promoted Baylis-Hillman reactions, along with a plausible reaction mechanism based on the previous findings and our own results.…”

Section: Introductionmentioning

confidence: 76%

Amine and Titanium (IV) Chloride, Boron (III) Chloride or Zirconium (IV) Chloride-Promoted Baylis-Hillman Reactions

2001

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The Baylis-Hillman reactions of various aryl aldehydes with methyl vinyl ketone at temperatures below -20oC using Lewis acids such as titanium (IV) chloride, boron (III) chloride or zirconium (IV) chloride in the presence of a catalytic amount of selected amines used as a Lewis bases afford the chlorinated compounds 1 as the major product in very high yields. Acrylonitrile can also undergo the same reaction to give the corresponding chlorinated product in moderate yield. A plausible reaction mechanism is proposed. However, if the reaction was carried out at room temperature (ca. 20oC), then the Z-configuration of the elimination product 3, derived from 1, was formed as the major product.

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Section: Introductionmentioning

confidence: 76%

Amine and Titanium (IV) Chloride, Boron (III) Chloride or Zirconium (IV) Chloride-Promoted Baylis-Hillman Reactions

2001

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“…Treatment of 4 a -c and 5 a -c with titanium(IV) chloride in refluxing chloroform for 1 hour caused intramolecular cyclocondensation to afford the corresponding tetrahydrothieno[2,3-b]pyridines 6a-c and 7a-c. Interestingly, we found the milder condition under which compounds 6a-c and 7a-c could be obtained in the presence of titanium(IV) chloride and triethylamine ( Table 2). Several investigators have reported an efficient transformation and cyclization by the action of a titanium(IV) chloride-amine combination [32][33][34][35]. In our reaction, it seems likely that since the rate of intramolecular cyclocondensation of 4 and 5 could be promoted by using triethylamine as the base at low temperature, 6a-c and 7a were obtained in somewhat better yields of 51, 44, 60 and 75%, respectively (entries 2, 4, 6 and 8).…”

Section: Pyridinesmentioning

confidence: 81%

Synthesis of dihydrothieno[2,3‐b]pyridines based on titanium(IV) chloride‐mediated michael reactions of 2‐amino‐4,5‐dihydro‐3‐thiophenecarbonitriles with α,β‐unsaturated ketones

Maruoka

Yamazaki

Tomioka

2004

Journal of Heterocyclic Chem

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2-Amino-4,5-dihydro-3-thiophenecarbonitriles 1 a -c reacted with α,β-unsaturated ketones (e . g . m e t h y l vinyl ketone 2 and benzalacetone 3) in the presence of titanium(IV) chloride to give the corresponding Michael adducts 4a-c and 5a-c. Thermal treatment of compounds 4a-c and 5a-c with titanium(IV) chloride caused intramolecular cyclocondensation to yield the corresponding tetrahydrothieno [2,3-b] pyridines 6a-c and 7a-c. Aromatization of 6a-c and 7a-c with potassium tert-butoxide in refluxing tert-butyl alcohol proceeded smoothly to afford the corresponding dihydrothieno[2,3-b]pyridines 8a-c and 9a-c.

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“…Acrylates are normally very unreactive in Lewis acid catalyzed BH reactions, and very low to zero yields of coupling products are obtained 6b. 7c,7d Interestingly, our new methodology works very well for both electron‐poor and electron‐rich aromatic aldehydes, giving excellent yields of Baylis–Hillman products in only 10 min (entries 3–7). When acrylonitrile was employed, reactions with aromatic aldehydes also gave high product yields (entries 8 and 9).…”

Section: Baylis–hillman Reactions Of Aldehydes With Cyclic Enones Catmentioning

confidence: 92%

A Highly Active and Selective Catalyst System for the Baylis–Hillman Reaction

You

Verkade

2003

Angewandte Chemie

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The Baylis-Hillman (BH) reaction, i.e., coupling of an activated alkene or alkyne with an aldehyde or ketone, has recently become a very attractive goal.[1] These reactions usually require Lewis bases as catalysts, such as tertiary phosphanes or tertiary amines, among which 1,4-diazabicyclo[2.2.2]octane (DABCO) is the most popular. However, this approach suffers from slow reaction rates (reaction times of weeks and even months [1,2] ) which limit the scope of substrates. Numerous chemical and physical methods have been developed to accelerate BH reactions. [1,3] One of the Lewis acids typically used to activate the carbonyl group [4] is TiCl 4 , used with or without additives (e.g., quaternary ammonium salts, an organic chalcogenide, phosphanes, a diol or a bisoxazoline). [1,4,5] Although the rates of BH reactions are improved significantly with the assistance of TiCl 4 , the yields are generally only moderate, and limitations are encountered on the structures of the Michael acceptors and the aldehydes which undergo addition, frequently producing complex mixtures. [5][6][7] The commercially available bicyclic proazaphosphatranes 1 a-1 c, first synthesized in our laboratories, have attracted considerable interest in recent years as versatile, exceedingly strong nonionic bases and as catalysts for a variety of useful transformations.[8] Recently, we reported that in the presence of proazaphosphatrane 1 c, activated allylic compounds such as acrylonitrile react efficiently with aromatic aldehydes to afford BH adducts as the only product.[9] However, when activated alkenes (cyclohex-1-en-1-one, vinyl ketones, acrylates, and allyl cyanide) were used as substrates in the presence of 1 a-1 c, the BH reactions failed whether with or without a Lewis acid (TiCl 4 or AlCl 3 ) present. Herein we report the surprising discovery that the proazaphosphatrane sulfide 2 a, easily prepared from commercially available 1 a, facilitates unparalleled speed and selectivity in BH reactions catalyzed by TiCl 4 .Initially, we examined the model reaction of p-nitrobenzaldehyde (1 mmol) with comparatively unreactive cyclohex-2-en-1-one (3 mmol) in CH 2 Cl 2 (2 mL) under argon at room temperature.[10] When 20 mol % catalyst 2 a was employed without any additives, this reaction gave only a 5 % product yield (based on the aldehyde) after four days. However, we found that the rate improved remarkably when one equivalent of some Lewis acids was added. After screening a variety of such acids (e.g., MgSO 4 , BF 3 ·OEt 2 , BCl 3 , SnCl 4 , AlCl 3 , Ti(OiPr) 4 , and TiCl 4 ), we found that TiCl 4 gave the best results. The model reaction carried out in the presence of 20 mol % 2 a and 1.0 equiv of TiCl 4 gave a 95 % yield of the product in only 5 min at room temperature. [11] Even with as little as 5 mol % 2 a, a 94 % yield was observed in 10 min at room temperature. Proazaphosphatrane sulfides 2 b and 2 c showed slightly reduced activities over the same time period (perhaps due to steric hindrance of the R group), giving yields of 85 and 78 %, respe...

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Titanium(IV) Chloride and the Amine-Promoted Baylis−Hillman Reaction

Cited by 90 publications

References 15 publications

Amine and Titanium (IV) Chloride, Boron (III) Chloride or Zirconium (IV) Chloride-Promoted Baylis-Hillman Reactions

Amine and Titanium (IV) Chloride, Boron (III) Chloride or Zirconium (IV) Chloride-Promoted Baylis-Hillman Reactions

Synthesis of dihydrothieno[2,3‐b]pyridines based on titanium(IV) chloride‐mediated michael reactions of 2‐amino‐4,5‐dihydro‐3‐thiophenecarbonitriles with α,β‐unsaturated ketones

A Highly Active and Selective Catalyst System for the Baylis–Hillman Reaction

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