Trapping of Carbenes using DMF or DMSO

Jens Wutke and Klaus Banerta

aChemnitz University of Technology, Institute for Chemistry, Organic Chemistry

Straße der Nationen 62, D-09111 Chemnitz, Germany

Introduction

Experimental proceeding in the laboratory:

� Variation of the amount of used azide (1,2,10 eq referring to 1)

� Investigation of the influence of water

� Marking experiments using D217O

� Synthesis of proposed intermediates and their reactionunder usual conditions (rt, 3 d, DMF)

� Attempts to trap assumed intermediates from the reaction of 1with ionic azides in dimethylformamide

We thank Dipl.-Chem. Dieter Schaarschmidt, Dr. Tobias Rüffer and Dr. Petra Ecorchard (Inorganic Chemistry, Chemnitz University of Technology) for the X-ray crystal structure measurements. We are also very thankful to Dr. Manfred Hagedorn for his support of our work.

[1] W. Kirmse, Carbene, Carbenoide und Carbenanaloge, Verlag Chemie, Weinheim, 1969.

[2] A. J. Arduengo III, R. L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361.

[3] K. Banert, M. Hagedorn, J. Wutke, P. Ecorchard, D. Schaarschmidt, H. Lang, Chem. Commun., in preparation.

[4] A. A. Auer, E. Prochnow, K. Banert, J. Phys. Chem. A 2007, 111, 9945–9951.

[5] F. Dost, J. Gosselck, Tetrahedron Lett. 1970, 11, 5091–5093.

Mechanistical Investigation (Formation of 10) Summary

Carbene Trapping Structures

Possible Mechanistical Pathways to 10 Inter- and Intramoleculare Carbene Trapping

Molecular structure of 9b(R = p-CH3–C6H4–)

Molecular structure of 7a (R = Ph–)

Quantum-chemicalcalculations have shown

that the corresponding nitre-ne structure resulting from 2does not meet an energetic

minimum.[4]

Severalmechanisms canbe postulated to ex-plain the formation of theα-oxo amides 10. We have shownthat nitrile 11a is converted into 10ain up to 8 % yield, what give reason tosuspect an insertion of the carbenes 5 intothe (sp2)-CH-bond of DMF as a possible reactionpathway.

Molecular structure of 10c(R = p-Ph–C6H4–)

Molecular structure of 11a

Molecular structureof 9e

Molecular structure of 20

Within our attempts to synthesize 1-azido-1-alkynes 2,[3] we have demonstrated that these compounds are highly reactive species leading to carbene structures 5which have successfully been trapped as shown below. Whereas widely used trapping agents such as cyclohexene (� 6), tolane (� 7) and cyclooctyne (� 8) gave no or only small amounts of carbene trapping products, we have been able to show polar solvents such as DMSO (� 9) and DMF (� 10) to be suitable reagents for “catching” the intermediates 5 in moderate yields.

Carbenes are short-lived neutral species containing a carbon atom with only six valence electrons. Thus, they are electron-deficiency compounds, which are able to take part in several kinds of reactions, such as the formation of three-memberedrings, insertions or ring enlargement reactions, for instance.[1]

Although persistent carbenes are known (Arduengo carbenes),[2] most members of the carbene family are highly reactive intermediates which have to been proved by defined trapping products, due to their reactivity. However, the generation of carbe-nes can easily be performed using diazoalkanes, ketenes, diazirines or α-elimination.

On the otherhand, the formation

of heterocycle 20 mightbe a result from an intramo-

lecular reaction based on the cor-responding oxirane 14d. Although the

reaction of carbenes with DMSO has alreadybeen described in literature,[5] a trapping of car-

benes using DMF has surprisingly not been reported, yet.

R

Cl

R = CH2OTHP

DMFrt, 3 d

NaN3

O

ONMe2

R = CH2OH

DMFrt, 3 d

NaN3

53%

34%

O OO

NMe2ODMSOrt, 3 d

NaN3

1R

9

CN

SMeMe

O

= THP (tetrahydro- pyran-2-yle)

a d e

10e

R = CH2OHNaN3

OH

5d

CN intramolecularreaction

up to 4.8% O

CN

Cl

CHOHCN

52%

19 18

20

R = HR = CH2OH R = CH2OTHP

10% 3.9% 25%

DMSOrt, 2 d

14%

sulfolane

We have been able to show DMSO as well as DMF to be suitable agents for thetrapping of carbenes but in the last case the reaction might be limited to carbenes bearing a good leaving group in α-position. Whereas the formation of sulfoxonium ylides 9 is easily understandable, the reaction involving dimethylformamide yieldingα-oxo amides 10 is still not understood completely. We postulated several possiblereaction pathways and tried to identify different intermediates regarding to theconfirmation of these mechanism. A few tests including 17O marking experimentsare still in progress to achieve certain knowledge.

© Timo Pries, http://www.comic-labor.de

–NaClPh

Cl

Ph

CN

mechanism 1:insertion into the (sp2)-CH-bond of DMF

Me2NO

H

Ph

CNNMe2

H

O

mechanism 2:addition to the CO-bond of DMF

Ph

CN

O

H

NMe2

Me2NO

H

1a

Ph

NuNMe2

H

OPh

NHNMe2

O

H2O

Nu–

–CN–Ph

O

Nu

NMe2H

Ph

O

NH

NMe2Nu=N3

–N2

H2ONu=OH

oxidation

5a

Nu–

–CN–

Nu=N3

–N2

PhNMe2

O

O

11a 12a 13a

14a 15a 16a

Nu=OH

oxidation

10a

N N

Ph Br17

TBACNDMFrt, 3d

up to 13%

NaN3

–N2

up to 21% (from 1a)

DMF

R Cl R N3

N3–

–Cl–R CN

R CN

NN

–N2 –N2 R Br

NNTBACN

1 2 345

R CN6

not observed

tolane

R CN7

a R=Ph 1.2%

Ph Ph

R CN8

up to 2.3%

cyclo octyneDMSO

R CN9

up to 25%

R O10

up to 53%

DMF

SH3C CH3

OO N(CH3)2