Moss et al.
(R)- and (S)-diazirine precursors. We attribute the prod-
ucts to fragmentations of carbenes (S)-8 and (R)-8, which
are generated by the photolysis or thermolysis of
diazirines (S)-11 and (R)-11, respectively.
To define the stereochemistry of the (S)-8 or (R)-8
conversions to chlorides 4, 5, and 7, we need the absolute
configurations and associated rotational properties of the
products. This information was unknown when we began
our studies, so we computed it.9,20 The structures of 4, 5,
and 7 were minimized at the DFT-RB3LYP level with
the 6-31G(d) basis set, and the optical rotations at the
sodium D line were calculated with RB3LYP/6-311++G-
(2d,p) from the Gaussian 03 suite.21The computed con-
nection between absolute configuration and calculated
specific rotation for each of the product chlorides is shown
below, where the computed [R]D value pertains to solvents
such as CH2Cl2 or CHCl3.9
FIGURE 1. Separation of a mixture of racemic chlorides 4,
5, and 7 on a Chiraldex GTA column at 50 °C. The numbers
are retention times in minutes. From left to right the peak
assignments are (R)-4, (S)-4, (R)-5, (S)-5, (S)-7, and (R)-7.
1 cm cell (c 0.0048, CDCl3).22 The dextrorotatory char-
acter of this material establishes it as the (R)-enantiomer
(see above). In parallel fashion, we obtained samples of
(S)-(-)-5 with RD25 -0.117 (c 0.0167, CDCl3) and (S)-(+)-4
25
with RD 0.008 (l ) 0.1 dm, c ) 0.002, CDCl3).23
With chloride samples of known absolute configuration
thus in hand, we could assign peak identities in GC
separations of the enantiomeric chloride products from
fragmentations of carbenes 3, 6, and 8. Product mixtures
were analyzed on a 30 m × 0.25 mm Chiraldex GTA
column at 50 °C, where both enantiomers of each of the
chlorides 4, 5, and 7 could be separated. Figure 1
illustrates the separation of a mixture of the three
racemic chlorides. For separations of product mixtures
from the fragmentations of the enantiomerically enriched
carbenes, product GC peak areas were electronically
integrated.
Samples of (S)-(+)-4, (S)-(-)-5, and (R)-(+)-7 were
obtained by chromatographic separations of the product
mixtures from the fragmentations of (S)-exo-5-norbor-
nenyl-2-oxychlorocarbene [(S)-3],9 (S)-nortricyclyloxy-
chlorocarbene [(S)-6],10 and (R)-endo-5-norbornenyl-2-
oxychlorocarbene [(R)-8] (this work). For example, (R)-
endo-5-norbornen-2-ol,13,14 via the derived isouronium salt
(R)-10 and diazirine (R)-11, ultimately afforded carbene
(R)-8, which gave endo-2-chloro-5-norbornene. The puri-
Stereochemical Results. (S)-(-)-5-Norbornen-2-ol,
(S)-(-)-9 with [R]D -113, 68.5% ee,15,16 was converted
25
to isouronium salt (S)-10 and then to diazirine (S)-11 as
described above. Photolysis or thermolysis of (S)-11 in
cyclohexane-d12, CDCl3, or CD3CN afforded chloride
mixtures via carbene (S)-8 which were analyzed on the
Chiraldex capillary GC column. The product ee’s and the
% ee’s of the conversions are collected in Table 2,
corrected for the 68.5% ee assumed for carbene (S)-8.
Given that enantiomeric carbene (R)-8 was available
from an analogous sequence beginning with alcohol (R)-
9, we could obtain an independent check on the stereo-
chemistry of product formation. The product ee’s and %
ee’s of a parallel series of conversions via fragmentations
of (R)-8 are collected in Table 3, corrected for the 73.3%
ee assumed for carbene (R)-8 derived from (R)-9 with
25
fied 4.8 mg sample had RD 0.034 ( 0.002, as read in a
(20) For examples of the assignment of absolute configuration by
ab initio theory and the calculation of [R]D, see: (a) Kondru, R. K.;
Wipf, P.; Beratan, D. N. J. Am. Chem. Soc. 1998, 120, 2204. (b) Kondru,
R. K.; Wipf, P.; Beratan, D. N. Science 1998, 282, 2247. (c) Ribe, S.;
Kondru, R. K.; Beratan, D. N.; Wipf, P. J. Am. Chem. Soc. 2000, 122,
4608. (d) Specht, K. M.; Nam, J.; Ho, D. M.; Berova, N.; Kondru, R.
K.; Beratan, D. N.; Wipf, P.; Pascal, R. A.; Kahne, D. J. Am. Chem.
Soc. 2001, 123, 8961. Review: (e) Polavarapu, P. L. Chirality 2002,
14, 768.
(21) Gaussian 03, Revision B.03: Frisch, M. J.; Trucks, G. W.;
Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Montgomery, J. A.; Jr,; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam,
J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.;
Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador,
P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M..C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari,
K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.;
Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; and Pople, J. A.,
Gaussian, Inc., Pittsburgh, PA, 2003.
[R]D 121, 73.3% ee.15,16
25
Examination of the sterochemical results in Tables 2
and 3 reveals a reasonable consistency: there are only
small differences between the ee’s of products formed by
photochemical or thermal decompositions of diazirine (S)-
11 or (R)-11 (i.e., carbene (S)-8 or (R)-8), and the product
(22) Optical rotations were obtained on an automated polarimeter;
readings were reproducible to (0.002°.
(23) The observed rotation of (S)-(+)-4 is admittedly small, but the
consequent dextrorotatory assignment to the (S)-enantiomer verifies
that the fragmentation of carbene (S)-3 to chloride 4 (now assigned as
(S)-4) occurs with 90-100% retention in cyclohexane, in keeping with
the computed SNi mechanism.9
8456 J. Org. Chem., Vol. 70, No. 21, 2005