Organic Letters
Letter
as there is no such conceivable pathway for 14 and species 15
would not spontaneously dissociate the Br− ion analogously to
3 (ΔG = 33 kcal/mol vs −3 kcal/mol)22 as this would lead to
the high energy singlet 1CNN (estimated to be ca. 24 kcal/mol
above 1c-CN2).23 Ion 15 would then more likely be protonated
to afford bromodiazomethane (16), readily denitrogenating to
bromomethylene (17),24 rather than exchanging its halogen to
form 11. It should be, however, pointed out that carbene 17
can give rise to acetals 7 by an O−H insertion resulting in
bromoether 18 followed by a nucleophilic halogen displace-
ment.
REFERENCES
■
(1) (a) Moskaleva, L. V.; Lin, M. C. J. Phys. Chem. A 2001, 105, 4156.
(b) Jursic, B. S. THEOCHEM 1999, 491, 33. (c) Martin, J. M. L.;
Taylor, P. R.; Franco̧ is, J. P.; Gijbels, R. Chem. Phys. Lett. 1994, 226,
475. (d) Kassaee, M. Z.; Ghambarian, M.; Musavi, S. M.; Shakib, F. A.;
Momeni, M. R. J. Phys. Org. Chem. 2009, 22, 919. (e) Gronert, S.;
Keeffe, J. R.; More O’Ferrall, R. A. J. Am. Chem. Soc. 2011, 133, 3381.
(2) (a) Milligan, D. E.; Jacox, M. E.; Bass, A. M. J. Chem. Phys. 1965,
43, 3149. (b) Milligan, D. E.; Jacox, M. E. J. Chem. Phys. 1966, 44,
2850.
(3) (a) Heinemann, C.; Muller, T.; Apeloig, Y.; Schwarz, H. J. Am.
Chem. Soc. 1996, 118, 2023. (b) Boehme, C.; Frenking, G. J. Am.
Chem. Soc. 1996, 118, 2039. (c) Tafipolsky, M.; Scherer, W.; Ofele, K.;
Artus, G.; Pedersen, B.; Herrmann, W. A.; McGrady, G. S. J. Am.
̈
Consistently with the substantial endothermicity of the ring
̈
1
1
opening of c-CN2 to CNN, the calculated activation energy
for this process is high (EA = 67 kcal/mol).17 The opening of
1c-CN2 to 1NCN is energetically almost neutral (ΔE = −2 kcal/
mol),25 with a high estimated barrier (EA ≈ 66 kcal/mol).26 All
the above calculations thus show that c-CN2 and its anionic
derivatives 3 and 5 are kinetically stable to the ring-opening
reactions on the singlet potential energy surface.
Chem. Soc. 2002, 124, 5865.
́
(4) Martinu, T.; Bohm, S.; Hanzlova, E. Eur. J. Org. Chem. 2011,
̊
̈
6254.
(5) Pyykko, P.; Runeberg, N. Chem.Asian J. 2006, 1, 623.
́
es, S., Ed.; The Royal
̈
(6) N-Heterocyclic Carbenes; Díez-Gonzal
Society of Chemistry: Cambridge, 2011.
(7) Moss, R. A. Acc. Chem. Res. 2006, 39, 267.
Other possible precursors of products 2 and 7 (but not 9)
obtained upon fragmentation of 1 are DMF itself (the solvent
used) and dialkoxyesters 19 potentially formed from 1 by a
halogen exchange/denitrogenation/O−H insertion sequence.
Both alternatives can be excluded, as the cleavage of 1 also
proceeds in DMSO, no deuterium incorporates to 7 when the
reaction is performed in DMF-d7, and an authentic sample of
19 (R = Bu) does not afford any 2 or 7 when subjected to the
cleavage reaction conditions.4
In conclusion, experimental and computational results
indicate that bromodiazirine esters 1 undergo a nucleophilic
displacement at the ester group. While the reaction of butyl
ester 1a with amines in methanol affords amides, the reaction
with alkoxide ions in DMF leads to the expulsion of the
c‑CN2Br− ion, likely dissociating to the c-CN2 carbene. In the
presence of a pent-4-en-1-ol, this elusive species gives rise to
pentenoxymethylenes undergoing O−H insertion and intra-
molecular [2 + 1] cycloaddition reactions. Alternative pathways
have been shown to be inconsistent with experimental
observations, and the c-CN2 ring of the parent carbene and
its anionic derivatives has been calculated to be kinetically
stable to opening.
(8) Diazirinyl anions (c-CN2R−), cyclic 4π-electron systems, are in
fact nonaromatic. They have been observed in the gas phase or
implicated as reactive intermediates in solution: (a) Kroeker, R. L.;
Bachrach, S. M.; Kass, S. R. J. Org. Chem. 1991, 56, 4062. (b) Kroeker,
R. L.; Kass, S. R. J. Am. Chem. Soc. 1990, 112, 9024. (c) Seburg, R. A.;
Hill, B. T.; Jesinger, R. A.; Squires, R. R. J. Am. Chem. Soc. 1999, 121,
6310. (d) Creary, X.; Sky, A. F.; Phillips, G.; Alonso, D. E. J. Am.
Chem. Soc. 1993, 115, 7584. (e) Moss, R. A.; Xue, S.; Liu, W. G. J. Am.
Chem. Soc. 1994, 116, 10821.
(9) Excess amine was avoided to prevent the halogen exchange
reaction leading to aminodiazirines: Moss, R. A.; Cox, D. P.; Tomioka,
H. Tetrahedron Lett. 1984, 25, 1023.
(10) The reaction also readily proceeds in DMSO (with lower
isolated yields of 2), it is very slow in methanol or butan-1-ol, and it
does not proceed in THF or hexane.
(11) Jones, M.; Moss, R. A. In Reactive Intermediate Chemistry; Moss,
R. A., Platz, M. S., Jones, M., Eds.; Wiley: Hoboken, NJ, 2004; p 273.
(12) (a) Inoue, Y.; Matsumoto, N.; Hakushi, T.; Srinivasan, R. J. Org.
Chem. 1981, 46, 2267. (b) Anderson, J. C.; Lindsay, D. G.; Reese, C.
B. Tetrahedron 1964, 20, 2091.
(13) Taylor, K. G.; Hobbs, W. E.; Saquet, M. J. Org. Chem. 1971, 36,
369.
(14) The formation of sodium alkoxide using NaH was performed
first in THF in order to prevent concomitant alcoholysis of DMF
known to complicate the diazirine cleavage reaction (ref 4).
(15) See the Supporting Information for the syntheses of alcohols
8b−d.
ASSOCIATED CONTENT
■
S
* Supporting Information
(16) Bel
2005, 70, 291.
́ ́ ̂
anger, G.; Levesque, M.; Paquet, J.; Barbe, G. J. Org. Chem.
Experimental procedures, spectroscopic data for all new
compounds, computational details. This material is available
(17) Calculated at the MP4(SDTQ)/aug-cc-pVTZ//MP2/aug-cc-
pVTZ level in DMF (CPCM solvation model).
(18) According to the NPA at the MP2/6-311+G(d) level in DMF
(CPCM solvation model), the c-CN2 ring carries 2% of the total
negative charge in bromo anion 3 and 55% in alkoxy anion 5
(methoxy-substituted model 5′).
(19) Moss, R. A.; Zhang, M.; Krogh-Jespersen, K. Org. Lett. 2009, 11,
5702.
(20) Hine, J.; Langford, P. B. J. Am. Chem. Soc. 1957, 79, 5497.
(21) This phenomenon has been explained by strong proton
solvation in DMF through hydrogen bonding: Corey, E. J.; Link, J. O.;
Shao, Y. Tetrahedron Lett. 1992, 33, 3435.
AUTHOR INFORMATION
■
Corresponding Author
Notes
The authors declare no competing financial interest.
(22) Calculated at the MP2/6-311+g(d) level in DMF (CPCM
ACKNOWLEDGMENTS
■
solvation model).
This work was supported by the Specific University Research
Grant MSMT 21/2013 from the Ministry of Education, Youth
and Sports of the Czech Republic. We thank Dr. Christopher J.
Shaffer for helpful discussions and Ms. Kvet
technical assistance.
1
3
(23) Based on the calculated relative energies of c-CN2 and CNN
(ref 1a) and the measured ΔES−T = 19.5 kcal/mol of CNN (Clifford,
E. P.; Wenthold, P. G.; Lineberger, W. C.; Petterson, G. A.; Broadus,
K. M.; Kass, S. R.; Kato, S.; DePuy, C. H.; Bierbaum, V. M.; Ellison, G.
B. J. Phys. Chem. A 1998, 102, 7100).
̌ ́ ́
a Bartova for
854
dx.doi.org/10.1021/ol4036243 | Org. Lett. 2014, 16, 852−855