exo- and endo-2-Norbornyloxychlorocarbenes
J. Am. Chem. Soc., Vol. 123, No. 33, 2001 8115
norborneol, 3.54 g (13.6 mmol) of triphenylphosphine, and 20 mL of
CCl4. The mixture was refluxed for about 2 h and then cooled to room
temperature. The CCl4 was distilled off and the residue was extracted
with 20 mL of acetonitrile. The volume of acetonitrile was reduced to
about 5 mL by rotary evaporation. The resulting MeCN solution of
2-norbornyl chlorides was analyzed by GC and GC-MS; the ratio of
exo- and endo-2-norbornyl chlorides (8/9) was 1.5/1. The exo chloride
was coeluted with a commercial sample (Aldrich).
Nortricyclene.36 Norcamphor tosylhyrazone was prepared by com-
bining p-toluenesulfonylhydrazine (2.7 g, 14.5 mmol) and 1.6 g (14.5
mmol) of norcamphor in 30 mL of 1% sulfuric acid in ethanol. The
solution was heated (55 °C, 5 min), poured into ice water, and allowed
to cystallize, affording the tosylhydrazone in near quantitative yield;
mp 200-202 °C, lit.36 mp 201.5-202.5 °C.
A three-neck flask was equipped with a magnetic stirring bar,
dropping funnel, nitrogen inlet, and a 30 cm Vigreux column. The latter
was connected to a series of 2 traps which were cooled with dry ice-
acetone. Nitrogen gas was led through the inlet and served to sweep
the volatile reaction products into the traps. A suspension of 1.93 g
(37 mmol) of sodium methoxide was suspended in 25 mL of diglyme
and heated in the flask to 160 °C. A solution of 3.0 g (11 mmol) of
norcamphor tosylhydrazone in 50 mL of diglyme was added dropwise
over 1.5 h to the hot base. Then, the contents of the two traps were
diluted with ∼15 mL of water and extracted with 3 × 15 mL of pentane.
The combined pentane extract was dried over CaCl2, filtered, and freed
of pentane by careful distillation, yielding 0.41 g (40%) of nortricyclene.
1H NMR37 (δ, CDCl3): 0.97 (s, 3 H, H1, H2, H6); 1.19 (s, 6 H, 2H3,
2H5, 2H7); 1.91 (s, 1 H, H4).
exo-2-Norbornyl Methyl Ether (12).38 To 0.94 g (10 mmol) of
norbornene and 0.48 g (15 mmol) of methanol in 10 mL of dry CH2-
Cl2 was added 1.23 mL (10 mmol) of BF3-etherate. The mixture was
stirred for 15 min at 25 °C and then quenched by addition of 20 mL of
aqueous NaHCO3. The organic phase was retained; the aqueous layer
was extracted with 3 × 5 mL of CH2Cl2; the organic phase and the
extracts were combined. Drying (CaCl2), filtration, and rotary evapora-
tion were followed by short-path distillation (60-62 °C, 15 Torr) to
give 1.25 g (64%) of 12. 1H NMR (δ, CDCl3): 0.92-1.13, 1.29-1.60
(m’s, 8 H, norbornyl); 2.22 and 2.33 (m’s, 1 H each, bridgeheads);
3.26, (s, 3 H, CH3); 3.20-3.80 (m, 1 H, CHO).
Photolysis of Diazirines. LFP experiments employed the system
described in detail in ref 12b. LFP-TRIR experiments were performed
at Johns Hopkins University.25 For all product studies, solutions of exo-
or endo-6 in MeCN or DCE (A356 ) 1.0) were photolyzed at 25 °C for
1 h with a focused Oriel lamp, λ > 320 nm (uranium glass filter).39
The products were analyzed by capillary GC (or GC-MS) using a 30
m × 0.25 mm (o.d.) × 0.25 µm (i.d.) CP-Sil 5CB (100% dimethyl
polysiloxane) column at 40 °C (3 min), programmed to 150 °C at 10
deg/min. Products are described above; see Tables 1-3. Product
identities were confirmed by GC and GC-MS comparisons to authentic
samples.
Phase Transfer Catalytic Generation of endo-7.32 A mixture of
endo-norborneol (0.56 g), 10 mL of 50% aqueous sodium hydroxide
solution, and 0.02 g of benzyltriethylammonium chloride was stirred
vigorously at 40 °C to emulsify it, and then 8 mL of CHCl3 was added
dropwise into the emulsion over 1 h. The mixture was stirred for a
further 2 h and then extracted with 20 mL of ether and washed with
water. The ether solution was analyzed by GC, which indicated the
presence of norbornene (55.8%), exo-norbornyl chloride (39.5%), and
endo-norbornyl chloride (4.7%). The products were identified by GC
comparisons to authentic samples. In a control experiment, a mixture
of exo- and endo-chlorides (8/9 ) 1.5) was vigorously stirred at 40 °C
with 50% aqueous NaOH solution and 20 mg of benzyltriethylammo-
of 9, and 55.8% of 10. Controls demonstrated the stability of
the reaction products to the experimental conditions. The
observed product distribution resembles that obtained from the
fragmentation of diazirine-derived endo-7 in DCE with added
TBACl (Table 2). The reported32 large yield of endo-chloride
and the absence of norbornene were not reproduced. The ion
pair mechanism for the fragmentations of carbenes 7, as
described above, remains our preferred rationale.
In conclusion, the fragmentations of exo- and endo-2-
norbornyloxychlorocarbenes occur at similar rates and transit
low energy barriers which lead to little exo/endo kinetic
differentiation. Ion pairs are formed which are geometrically
akin to the configuration and conformation of their precursor
carbenes; product distributions from exo- and endo-7 therefore
differ. In both cases, large quantities of norbornene form via
proton transfer from C3 to the chloride anion within the ion
pairs. The ion pairs that lead to norbornene can be competitively
intercepted by added methanol.
Experimental Section
Solvents. Acetonitrile (Fischer, Ceritified A. C. S.) and pyridine
(Fisher, Certified A.C.S.) were dried by reflux over CaH2, followed
by distillation and storage over 5A molecular sieves. Dichloroethane
(DCE) (Aldrich, Certified A.C.S.) was used without further treatment.
Pentane (Fisher, HPLC grade) was stored over 5A molecular sieves.
exo-2-Norbornylisouronium Trifluoromethanesulfonate (exo-5).
This material was prepared using the procedure described in ref 14.
endo-2-Norbornylisouronium trifluoromethanesulfonate (endo-
5). In a 50 mL one-neck round-bottom flask, equipped with a stirring
bar and a reflux condenser protected with a calcium chloride tube, were
placed 1.00 g (23.8 mmol) of cyanamide, 5.34 g (47.6 mmol) of endo-
norborneol, and 12 mL of anhydrous THF. To this solution was added
3.57 g (23.8 mmol) of trifluoromethanesulfonic acid. The mixture was
magnetically stirred at 55 °C (oil bath) for 30 h. After the reaction
mixture had been cooled to room temperature, it was diluted with 200
mL of pentane and refrigerated. A brown solid was harvested and
washed with 6 × 15 mL of ether to afford white crystals that were
dried under vacuum (25 °C, <1 Torr). We obtained 2.53 g of endo-5,
mp 109-111 °C. 1H NMR (δ, DMSO-d6): 0.99-2.20, 2.48-2.67 (m’s,
10 H, norbornyl); 4.87-5.02 (m, 1 H, CHO); 8.43 (br s, 4 H, 2NH2).
Anal. Calcd for C9H15F3N2O4S: C, 35.5; H, 4.93; N, 9.21. Found: C,
35.2; H, 4.66; N, 9.42.
3-Chloro-3-(exo-2-norbornyloxy)diazirine (exo-6). The general
procedure of Graham15 was followed. To 3.5 g of LiCl in DMSO was
added 1.0 g (3.3 mmol) of iosouronium salt (exo-5) and 50 mL of
pentane. The mixture was cooled to 20 °C and stirred magnetically.
Then, 200 mL of 12% commercial aqueous sodium hypochlorite
solution, saturated with NaCl, was slowly added. After the addition
was complete, stirring was continued for 15 min at 15 °C. The reaction
mixture was transferred to a separatory funnel containing 150 mL of
ice water, the aqueous phase was removed, and the pentane phase was
washed twice with ∼75 mL of ice water and then dried for 2 h over
CaCl2 at 0 °C. The pentane/diazirine solution was purified by
chromatography over Aldrich 200-400 mesh, 60 Å, silica gel, eluted
with pentane. The volume of pentane was reduced by rotary evaporation,
and replaced by acetonitrile (or DCE). The remaining pentane was then
removed by rotary evaporation at 0 °C. About 30 mL of an acetonitrile
1
(or DCE) solution of diazirine exo-6 resulted. H NMR (δ, CD3CN):
0.7-1.7, 2.15-2.25 (m’s 10 H, norbornyl); 3.90-4.00 (m, 1 H, CHO).
UV (pentane), λmax 359 nm. The yield of exo-6 was ca. 50%.
3-Chloro-3-(endo-2-norbornyloxy)diazirine (endo-6). This material
was prepared from isouronium salt endo-5 exactly as described for the
1
(36) Freeman, P. K.; George, D. E.; Rao, V. N. M. J. Org. Chem. 1964,
29, 1682.
(37) Kropp, P. J.; Adkins, R. L. J. Am. Chem. Soc. 1991, 113, 2709.
(38) Shellhamer, D. F.; Callahan, R. P.; Heasley, V. L.; Druelinger, M.
L.; Chapman, R. D. Synthesis 1997, 1056.
(39) Photolyses that included added salts or MeOH were carried out in
the same manner. In a control experiment, exo-chloride 8 was shown to be
stable in 1:1 MeOH/MeCN under the photolysis conditions.
isomeric diazirine, exo-6. H NMR (δ, CD3CN): 0.70-1.50, 1.50-
1.70 (m’s, 10 H, norbornyl); 3.96-4.12 (m, 1 H, CHO). UV (pentane),
λmax 352 nm. The yield of endo-6 was ca. 50%.
endo-2-Norbornyl Chloride (9).35 In a 50 mL round-bottom flask,
fitted with a reflux condenser, was placed 1.0 g (8.9 mmol) of exo-
(35) Weiss, R. G.; Snyder, E. I. Chem. Commun. 1968, 1358.