encyclopedia of reagents for organic synthesis || ethyl lithiopropiolate

ETHYL LITHIOPROPIOLATE 1 Ethyl Lithiopropiolate Li CO 2 R (R = Et) [72036-30-7] C 5 H 5 LiO 2 (MW 104.04) InChI = 1/C5H5O2.Li/c1-3-5(6)7-4-2;/h4H2,2H3;/rC5H5LiO2/ c1-2-8-5(7)3-4-6/h2H2,1H3 InChIKey = IODIHFTUTHBNNI-CNBQTQOEAZ (R = Me [72036-29-4] C 4 H 3 LiO 2 (MW 90.01) InChI = 1/C4H3O2.Li/c1-3-4(5)6-2;/h2H3;/rC4H3LiO2/c1-7- 4(6)2-3-5/h1H3 InChIKey = YUMFGLPOXLKNOB-KCGAAXSAAJ (R = t-Bu) [–] C 7 H 9 LiO 2 (MW 132.10) InChI = 1/C7H9O2.Li/c1-5-6(8)9-7(2,3)4;/h2-4H3;/rC7H9LiO2 /c1-7(2,3)10-6(9)4-5-8/h1-3H3 InChIKey = GQRQTHYGQKJFKY-FTYUVRRRAK (R = CH 2 CH=CH 2 ) [109907-88-2] C 6 H 5 LiO 2 (MW 116.05) InChI = 1/C6H5O2.Li/c1-3-5-8-6(7)4-2;/h3H,1,5H2;/rC6H5 LiO2/c1-2-5-9-6(8)3-4-7/h2H,1,5H2 InChIKey = NUGTVSUTVLMSNE-QYCXFINGAZ (used in synthesis of alkynic alcohols by addition to aldehydes, ketones, 1 or epoxides 2 ) Preparative Methods: by treating the alkyl propiolate (e.g. Methyl Propiolate) with Butyllithium at low temperature. 1 An alternative method uses Lithium Diisopropylamide (LDA). 2 Handling, Storage, and Precautions: alkynyllithium reagents are air- and moisture-sensitive. These reagents decompose above −78 ◦ C. The ethyl derivative seems to be slightly more stable than the methyl compound. Ethyl and methyl propiolate should be handled with caution. Synthesis of Propargyl Alcohols. The lithium reagent rapidly adds to a variety of aldehydes and ketones to give the alkynic alcohols (eqs 1 and 2). 1 These products may be converted into γ -butenolides and γ -lactones. 3 The use of Cerium(III) Chloride provides higher yields in some cases (eq 3). 4 O OH CO 2 Et (1) 85% Ph H O Ph OH 84% CO 2 Et (2) H O O N Li CO 2 Et OH O N (3) CeCl 3 80% CO 2 Et Synthesis of Homopropargyl Alcohols. In the presence of Boron Triﬂuoride Etherate the reagent will open epoxides to provide homopropargyl alcohols (eq 4). 5 Allyl and t-butyl lithiopropiolates have been used in applications where an easily removable protecting group is required. 6 O BnO Li CO 2 Me BnO OH CO 2 Me (4) BF 3 •OEt 2 84% Related Reagents. 3,3-Diethoxy-1-propene; Lithium Acetylide; Propynyllithium; 3-Tetrahydropyranyloxy-1-propyne. 1. Midland, M. M.; Tramontano, A.; Cable, J. R., J. Org. Chem. 1980, 45, 28. 2. Herrmann, J. L.; Berger, M. H.; Schessinger, R. H., J. Am. Chem. Soc. 1979, 101, 1544. 3. Midland, M. M.; Tramontano, A.; Kazubski A.; Graham, R. S.; Tsai, D. J. S.; Cardin, D. B., Tetrahedron 1984, 40, 1371. 4. Vedejs, E.; Dax, S. L., Tetrahedron Lett. 1989, 30, 2627. 5. Takano, S.; Shimazaki, Y.; Iwabuchi, Y.; Ogasawara, K., Tetrahedron Lett. 1990, 31, 3619. 6. Jungheim, L. N.; Sigmund, S. K., J. Org. Chem. 1987, 52, 4007. M. Mark Midland University of California, Riverside, CA, USA Avoid Skin Contact with All Reagents

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ETHYL LITHIOPROPIOLATE 1

Ethyl Lithiopropiolate

Li CO2R

(R = Et)[72036-30-7] C5H5LiO2 (MW 104.04)InChI = 1/C5H5O2.Li/c1-3-5(6)7-4-2;/h4H2,2H3;/rC5H5LiO2/

c1-2-8-5(7)3-4-6/h2H2,1H3InChIKey = IODIHFTUTHBNNI-CNBQTQOEAZ

(R = Me[72036-29-4] C4H3LiO2 (MW 90.01)InChI = 1/C4H3O2.Li/c1-3-4(5)6-2;/h2H3;/rC4H3LiO2/c1-7-

4(6)2-3-5/h1H3InChIKey = YUMFGLPOXLKNOB-KCGAAXSAAJ

(R = t-Bu)[–] C7H9LiO2 (MW 132.10)InChI = 1/C7H9O2.Li/c1-5-6(8)9-7(2,3)4;/h2-4H3;/rC7H9LiO2

/c1-7(2,3)10-6(9)4-5-8/h1-3H3InChIKey = GQRQTHYGQKJFKY-FTYUVRRRAK

(R = CH2CH=CH2)[109907-88-2] C6H5LiO2 (MW 116.05)InChI = 1/C6H5O2.Li/c1-3-5-8-6(7)4-2;/h3H,1,5H2;/rC6H5

LiO2/c1-2-5-9-6(8)3-4-7/h2H,1,5H2InChIKey = NUGTVSUTVLMSNE-QYCXFINGAZ

(used in synthesis of alkynic alcohols by addition to aldehydes,ketones,1 or epoxides2)

Preparative Methods: by treating the alkyl propiolate (e.g.Methyl Propiolate) with Butyllithium at low temperature.1

An alternative method uses Lithium Diisopropylamide(LDA).2

Handling, Storage, and Precautions: alkynyllithium reagents areair- and moisture-sensitive. These reagents decompose above−78 ◦C. The ethyl derivative seems to be slightly more stablethan the methyl compound. Ethyl and methyl propiolate shouldbe handled with caution.

Synthesis of Propargyl Alcohols. The lithium reagent rapidlyadds to a variety of aldehydes and ketones to give the alkynicalcohols (eqs 1 and 2).1 These products may be converted intoγ-butenolides and γ-lactones.3 The use of Cerium(III) Chlorideprovides higher yields in some cases (eq 3).4

CO2Et

(1)85%

Ph H

84%CO2Et

(2)

Li CO2Et

N(3)

CeCl380%

CO2Et

Synthesis of Homopropargyl Alcohols. In the presence ofBoron Trifluoride Etherate the reagent will open epoxides toprovide homopropargyl alcohols (eq 4).5 Allyl and t-butyllithiopropiolates have been used in applications where an easilyremovable protecting group is required.6

BnO Li CO2Me BnO

OH CO2Me(4)

BF3•OEt284%

Related Reagents. 3,3-Diethoxy-1-propene; LithiumAcetylide; Propynyllithium; 3-Tetrahydropyranyloxy-1-propyne.

1. Midland, M. M.; Tramontano, A.; Cable, J. R., J. Org. Chem. 1980, 45,28.

2. Herrmann, J. L.; Berger, M. H.; Schessinger, R. H., J. Am. Chem. Soc.1979, 101, 1544.

3. Midland, M. M.; Tramontano, A.; Kazubski A.; Graham, R. S.; Tsai,D. J. S.; Cardin, D. B., Tetrahedron 1984, 40, 1371.

4. Vedejs, E.; Dax, S. L., Tetrahedron Lett. 1989, 30, 2627.

5. Takano, S.; Shimazaki, Y.; Iwabuchi, Y.; Ogasawara, K., Tetrahedron Lett.1990, 31, 3619.

6. Jungheim, L. N.; Sigmund, S. K., J. Org. Chem. 1987, 52, 4007.

M. Mark MidlandUniversity of California, Riverside, CA, USA

Avoid Skin Contact with All Reagents