ETHYL β-(1-PYRROLIDINYL)ACRYLATE 1

Ethyl βββ-(1-Pyrrolidinyl)acrylate

NOEt

O

[53927-12-1] C9H15NO2 (MW 169.25)InChI = 1/C9H15NO2/c1-2-12-9(11)5-8-10-6-3-4-7-10/h5,8H,

2-4,6-7H2,1H3InChIKey = VFFHLZJSZHWXAJ-UHFFFAOYAS(E)[65651-80-1]InChI = 1/C9H15NO2/c1-2-12-9(11)5-8-10-6-3-4-7-10/h5,8H,

2-4,6-7H2,1H3/b8-5+InChIKey = VFFHLZJSZHWXAJ-VMPITWQZBP

(precursor to β-vinyllithium derivative; reactions with electro-philes yield cyclopentenones, butenolides, maleic acid deriva-

tives, and oxalacetic acid derivatives1,2)

Physical Data: mp 41–43 ◦C; bp 80–105 ◦C/10−3 mmHg.3

Solubility: sol most organic solvents (ethanol, ethyl acetate,dichloromethane, chloroform, THF).

Form Supplied in: colorless solid.Analysis of Reagent Purity: 1H NMR (CDCl3) δ 1.27 (t, J = 7

Hz, 3 H, CH3), 1.95 (m, 4 H, CH2CH2N), 3.30 (m, 4H, CH2N),4.16 (q, J = 7 Hz, 2 H, CH2O), 4.50 (d, J = 12.5 Hz, 1 H, 2-H),7.72 (d, J = 12.5 Hz, 1 H, 3-H); 13C NMR δ 14.7 (CH3), 25.3(CH2CH2N), 4.88 (CH2N), 58.5 (CH2O), 84.6 (2-C), 169.2 (1-C); IR (CHCl3) 1600 (C=C), 1665 (C=O) cm−1; UV (EtOH)287 nm (ε = 2600).4

Preparative Method: reaction of ethyl propiolate with pyrrolidinein acetonitrile at rt yields ethyl β-(1-pyrrolidinyl)acrylate in55% yield as a colorless solid.3,4

Purification: distillation under reduced pressure.Handling, Storage, and Precautions: store under nitrogen

protected from moisture.

Acrylates with functional groups (for instance, amino,hydroxy, mercapto moieties) in the β-position exhibit: (i) nucle-ophilic character at the α-position, permitting reactions with var-ious electrophiles; (ii) electrophilic character at the β-position,enabling nucleophilic exchange reactions which can be employedfor ring closure reactions; and (iii) CH acidity at the β-position(and/or α-position) which, for instance with strong lithiatingagents, leads to direct β-lithiation, thus generating highly versatilefunctionally substituted vinyllithium derivatives.5,6 Typicalexamples for ethyl β-(1-pyrrolidinyl)acrylate are shown below.

Reaction with Diazonium Salts. The reaction of ethylβ-(1-pyrrolidinyl)acrylate with diazonium salts as electrophilesleads to the formation of iminium hydrazone derivatives (1) whichcan be isolated in 65–90% yields (eq 1). These products can beconverted into imidazole derivatives by action of base (eq 2) orinto cinnoline derivatives (eq 3), depending on the substituents ofthe aromatic ring.7,8

Reaction with ααα-Amino Carbonyl Compounds. The reac-tion of ethyl β-(1-pyrrolidinyl)acrylate with α-amino carbonyl

compounds as nucleophiles in refluxing ethanol proceeds via 1,4-addition followed by elimination to give transamination interme-diates which cyclize immediately to yield 3-substituted pyrroles(eq 4).9

CO2Et

HN

H CO2Et

NNNH

R

R

N2+ BF4

–

(1)

BF4–

MeCN, rt

(1)

+

CO2Et

NNNH

R

(2)

(1)

N

NCO2Et

R

H2N

BF4–

+

R = H

base

+

CO2Et

NNNH

R

(3)BF4

–

(1)

NN

R

CO2Et

R = OMe

+

N

EtO

O EtO NPh

O

Me O

N

Ph

Me

O

EtO

H2NPh

OMe

(4)

EtOH, ∆

+

Vinylcarbanion Generation. Ethyl β-(1-pyrrolidinyl)acr-ylate can be converted by direct lithiation with tert-Butyllithiumbelow −100 ◦C into a β-vinyllithium derivative (2) (eq 5), whichcan be used as a C3 synthon for cyclization reactions. Reactionwith acrylates, aldehydes, or ketones as electrophilic–nucleophilicspecies leads to functionally substituted cyclopentenones (eq 6)and butenolides (eq 7).1 Many examples involving reactionswith heterocumulenes have been reported.2 For instance, addi-tion of Phenyl Isothiocyanate or Phenyl Isocyanate yields, aftercyclization, the thiomaleic anhydride derivative (eq 8) or theN-phenylmaleimide derivative (eq 9), respectively. Addition ofalkyl isocyanates does not lead to cyclization, and oxalacetic acidderivatives are obtained (eq 10). Similarly, addition of CarbonDioxide yields, after hydrolysis of the enamine, an oxalacetatederivative (eq 11).

Avoid Skin Contact with All Reagents

2 ETHYL β-(1-PYRROLIDINYL)ACRYLATE

CO2Et

N

CO2Et

N Li(5)

(2)

<–100 °C

t-BuLiTHF

CO2Et

N Li N

O

R1H

CO2RR2H

R1R2

RO2C

(6)

(2)

CO2Et

N Li N

O

O

R1R2

OR1

R2

(7)

(2)

CO2Et

N Li(8)

N

S

O

NPh

(2)

PhNCS

CO2Et

N Li(9)

N

NPh

O

O

(2)

PhNCO

CO2Et

N Li N

(2)

NHR

OEt

O

O

(10)RNCO

CO2Et

N Li

(2)

OH

OEt

O

O

(11)

O

CO2

1. Schmidt, R. R.; Talbiersky, J., Angew. Chem. 1978, 90, 220.

2. Schmidt, R. R.; Talbiersky, J.; Betz, R., Chem. Ber. 1982, 115, 2674.

3. Grinblat, E. I.; Postovskiï, I. Y., Dokl. Akad. Nauk SSSR 1960, 133, 847.

4. Kanner, C. B.; Pandit, U. K., Tetrahedron 1982, 38, 3597.

5. Schmidt, R. R., Bull. Soc. Chim. Belg. 1983, 92, 825.

6. Jatzke, H.; Evertz, U.; Schmidt, R. R., Synlett 1990, 191.

7. Kanner, C. B.; Pandit, U. K., Heterocycles 1978, 9, 757.

8. Kanner, C. B.; Pandit, U. K., Tetrahedron 1981, 37, 3513.

9. Alberola, A.; Andrés, J. M.; Gonzalez, A.; Pedrosa, R.; Vicente, M.,J. Chem. Soc., Perkin Trans. 1 1990, 2681.

R. R. Schmidt & K.-H. JungUniversität Konstanz, Konstanz, Germany

A list of General Abbreviations appears on the front Endpapers