Effect of supramolecular inclusion on the selectivity of 3-nortricyclanylidene

Full text of DOI:10.1021/jo005713e

J . Org. Chem. 2001, 66, 1517-1522
1517
Recent advances in carbene chemistry demonstrate
that constrictive hosts, like cyclodextrins (CyD’s)6 and
faujasite zeolites (FAU’s),7 are able to modify the selec-
tivity of the high-energy reaction intermediate.8 Thus,
we hypothesized that the confinement of 2 within the
nanoscopic cavities of CyD’s (Figure 1) and FAU’s (Figure
2) would inhibit the fragmentation reaction and foster
the 1,3 C-H insertion. Our reasoning was 2-fold: (1)
there may not be enough space within the hosts’ cavities
for the unraveling process, 2f9, and (2) distortion of the
carbene’s topology might concomitantly disfavor the
coarctate TS and allow the 1,3 C-H insertion, 2f8, to
finally occur.
The main challenge was to imbue the CyD’s and FAU’s
with a carbene precursor that is compatible with the
hosts and the standard inclusion complex (IC) prepara-
tion. The sodium salt 10 must be kept moisture-free and,
therefore, is incompatible with CyD’s and FAU’s, since
both contain adventitious water molecules. Besides,
cyclodextrin IC’s (CyD IC’s) are prepared from aqueous
solutions! Likewise, faujasite zeolite IC’s (FAU IC’s) are
prepared by loading the zeolite with a pentane solution
of the guest; salt 10 is insoluble in pentane. Therefore, a
3H-diazirine,9 3-azinortricyclane (1), was needed as a
precursor10 in lieu of the Bamford-Stevens reagent 10.
Yet, the synthesis and properties of this compound were
unreported.
Effect of Su p r a m olecu la r In clu sion on th e
Selectivity of 3-Nor tr icycla n ylid en e†
Murray G. Rosenberg‡ and Udo H. Brinker*
Institut fu¨r Organische Chemie, Universita¨t Wien,
Wa¨hringer Strasse 38, A-1090 Wien, Austria
E-mail: Udo.Brinker@univie.ac.at
Received October 31, 2000
In tr od u ction
3-Nortricycla nylidene(tricyclo[2.2.1.02,6]hepta n-3-
ylidene) (2) was originally generated via the Bamford-
Stevens reaction of the 3-nortricyclanone p-tosylhydra-
zone sodium salt (10) (Scheme 1).1 The formation of
quadricyclane (tetracyclo[2.2.1.0.2,603,5]heptane) (8) was
anticipated, from an intramolecular 1,3 C-H insertion
of the carbene, but was not observed. This is intriguing
because 2-norbornanylidene (bicyclo[2.2.1]heptan-2-
ylidene) (5), which merely lacks the C2-C6 bridge in 2,
undergoes 1,3 C-H insertion to form nortricyclane
(tricyclo[2.2.1.02,6]heptane) (3) in over 95% yield.2 Instead,
4-ethynylcyclopentene (9) was formed via cyclopropyl-
carbene fragmentation,3 a process similar to the well-
known Eschenmoser fragmentation.4 This carbene rear-
rangement is believed to proceed through a coarctate TS
that requires strict orbital alignment of the divalent
carbon with the cyclopropane ring; a bilateral symmetry
and an endocyclic configuration are requiredsboth of
which are perfectly exemplified by 2.5
Resu lts a n d Discu ssion
The preparation of diazirine 1 was successful, albeit
in only 6% yield from 3-nortricyclanone (16).11 The
R-cyclodextrin (R-CyD) and â-cyclodextrin (â-CyD) IC’s
† Carbenes in Constrained Systems. 7. For part 6, see: Krois, D.;
Bobek, M. M.; Werner, A.; Ka¨hlig, H.; Brinker, U. H. Org. Lett. 2000,
2, 315-318. Carbene Rearrangements. 55. For part 54, see: Bobek, M.
M.; Brinker, U. H. J . Am. Chem. Soc. 2000, 122, 7430-7431.
* Corresponding author. Phone: +43-1-4277-52121. Fax: +43-1-
4277-52140, U.S.A.
(5) (a) Herges, R. Angew. Chem., Int. Ed. Engl. 1994, 33, 255-276.
(b) For a related example of coarctate fragmentation of 2-furfurylcar-
benes, see: Khasanova, T.; Sheridan, R. S. J . Am. Chem. Soc. 1998,
120, 233-234.
(6) (a) Comprehensive Supramolecular Chemistry; Lehn, J .-M., Ed.;
Pergamon: New York, 1995; Vol. 3. (b) Szejtli, J . Chem. Intell. 1999,
5 (3), 38-45. (c) Pagington, J . S. Chem. Br. 1987, 23, 455-458. (d)
Saenger, W. Angew. Chem., Int. Ed. Engl. 1980, 19, 344-362. (e) Wenz,
G. Angew. Chem., Int. Ed. Engl. 1994, 33, 803-822. (f) Maheswaran,
M. M.; Divakar, S. J . Sci. Ind. Res. 1994, 53, 924-932.
(7) (a) Rouhi, A. M. Chem. Eng. News 2000, 78 (34), 40-47. (b)
Ramamurthy, V. In Photochemistry in Organized and Constrained
Media; Ramamurthy, V., Ed.; VCH: New York, 1991; pp 432-435. (c)
Alvaro, M.; Corma, A.; Garc´ıa, H.; Miranda, M. A.; Primo, J . J . Chem.
Soc., Chem. Commun. 1993, 1041-1042.
(8) (a) Brinker, U. H.; Buchkremer, R.; Kolodziejczyk, M.; Kupfer,
R.; Rosenberg, M.; Poliks, M. D.; Orlando, M.; Gross, M. L. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1344-1345. (b) Kupfer, R.; Poliks, M.
D.; Brinker, U. H. J . Am. Chem. Soc. 1994, 116, 7393-7398. (c) Kupfer,
R.; Brinker, U. H. Liebigs Ann. 1995, 1721-1725. (d) Rosenberg, M.
G.; Kam, S. M.; Brinker, U. H. Tetrahedron Lett. 1996, 37, 3235-3238.
(e) Brinker, U. H.; Rosenberg, M. G. Adv. Carbene Chem. 1998, 2, 29-
44.
(9) (a) Chemistry of Diazirines; Liu, M. T. H., Ed.; CRC: Boca Raton,
FL, 1987; 2 vols. (b) Schmitz, E. Adv. Heterocycl. Chem. 1963, 2, 83-
130. (c) Schmitz, E. Adv. Heterocycl. Chem. 1979, 24, 63-107. (d)
Schmitz, E. Angew. Chem., Int. Ed. Engl. 1964, 3, 333-341. (e)
Schmitz, E. In Methoden der Organischen Chemie (Houben-Weyl);
Klamann, D., Ed.; Thieme: Stuttgart, 1992; Vol. E16c, pp 678-728.
(10) (a) Schmitz, E.; Habisch, D.; Stark, A. Angew. Chem., Int. Ed.
Engl. 1963, 2, 548. (b) Du¨rr, H.; Abdel-Wahab, A.-M. A. In Organic
Photochemistry and Photobiology; Horspool, W. M., Ed.; CRC: Boca
Raton, FL, 1995; pp 954-983.
(11) (a) Meinwald, J .; Crandall, J . K. J . Am. Chem. Soc. 1966, 88,
1292-1301. (b) Meinwald, J .; Crandall, J .; Hymans, W. E. Org. Synth.
Coll. 1973, 5, 866-868. (c) Hall, H. K., J r. J . Am. Chem. Soc. 1960,
82, 1209-1215. (d) Upadek, H. Ph.D. Dissertation, Ruhr-Universita¨t
Bochum, Germany, 1977; pp 156-159.
‡Department of Chemistry, State University of New York, Bing-
hamton, NY 13902-6016.
(1) (a) Cristol, S. J .; Harrington, J . K. J . Org. Chem. 1963, 28, 1413-
1415. (b) Lemal, D. M.; Fry, A. J . J . Org. Chem. 1964, 29, 1673-1676.
(c) Arct, J .; Brinker, U. H. In Methoden der Organischen Chemie
(Houben-Weyl); Regitz, M., Ed.; Thieme: Stuttgart, 1989; Vol. E19b,
pp 337-375. (d) Sydnes, L. K.; Brinker, U. H. In Methoden der
Organischen Chemie (Houben-Weyl); Regitz, M., Ed.; Thieme: Stut-
tgart, 1989; Vol. E19b, pp 542-576. (e) Shapiro, R. H. Org. React. (NY)
1976, 23, 405-507. (f) Freeman, P. K.; George, D. E.; Rao, V. N. M. J .
Org. Chem. 1963, 28, 3234-3237. (g) Kirmse, W.; Kno¨pfel, N. J . Am.
Chem. Soc. 1976, 98, 4672-4674.
(2) (a) Friedman, L.; Shechter, H. J . Am. Chem. Soc. 1961, 83, 3159-
3160. (b) Freeman, P. K.; George, D. E.; Rao, V. N. M. J . Org. Chem.
1964, 29, 1682-1684. (c) Kirmse, W.; Meinert, T.; Modarelli, D. A.;
Platz, M. S. J . Am. Chem. Soc. 1993, 115, 8918-8927.
(3) (a) Shevlin, P. B.; McKee, M. L. J . Am. Chem. Soc. 1989, 111,
519-524. (b) Moss, R. A.; Liu, W.; Krogh-J espersen, K. J . Phys. Chem.
1993, 97, 13413-13418. (c) Moss, R. A. Pure Appl. Chem. 1995, 67,
741-747. (d) Huang, H.; Platz, M. S. J . Am. Chem. Soc. 1998, 120,
5990-5999. (e) Ammann, J . R.; Subramanian, R.; Sheridan, R. S. J .
Am. Chem. Soc. 1992, 114, 7592-7594. (f) Levashova, T. V.; Semeikin,
O. V.; Balenkova, E. S. J . Org. Chem. USSR 1980, 16, 53-56. (g)
Murray, R. K., J r.; Ford, T. M. J . Org. Chem. 1977, 42, 1806-1808.
(h) Freeman, P. K.; Pugh, J . K. J . Am. Chem. Soc. 1999, 121, 2269-
2273. (i) Bergman, R. G.; Rajadhyaksha, V. J . J . Am. Chem. Soc. 1970,
92, 2163-2164. (j) Wills, M. S. B.; Danheiser, R. L. J . Am. Chem. Soc.
1998, 120, 9378-9379.
(4) (a) Advanced Organic Chemistry, 4th ed.; March, J ., Ed.; Wiley:
New York, 1992; p 1037. (b) Hassner, A.; Stumer, C. Organic Syntheses
Based on Name Reactions and Unnamed Reactions; Pergamon: Tar-
rytown, NY, 1994; p 110. (c) Mundy, B. P.; Ellerd, M. G. Name
Reactions and Reagents in Organic Synthesis; Wiley: New York, 1988;
pp 72-73.
10.1021/jo005713e CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/23/2001

1518 J . Org. Chem., Vol. 66, No. 4, 2001
Sch em e 1. Gen er a tion of 3-Nor tr icycla n ylid en e (2) a n d Its Su bsequ en t Rea ction sa
Notes
a
i
RH ) (a) R-CyD, (b) â-CyD, (c) MeOH, (d) PrOH, (e) AcOH, (f) H2O, (g) c-C6H12; Ts ) p-SO2C6H4CH3.
wiched between two R-CyD units but that it forms a
2-fold 1:1 complex with â-CyD.15 It has been demon-
strated that a guest must have an electronegative group,
like -F or -OH,13,15 to effect an opposite inclusion
orientation within cyclodextrins in the aqueous versus
solid phase. Hence, it is likely that hydrophobic 1 adopts
the same orientation within CyD in both phases. The
FAU IC was prepared from 1 and thermally activated
NaY so as to give a loading factor ( s ) of ca. 0.25, which
corresponds to one filled supercage surrounded by four
empty ones.16
Supramolecular photolyses of the aforementioned IC’s
of 1 were carried out for at least 24 h each. Of the two
possible intramolecular products, 8 and 9, only 9 was
observed. Control experiments were performed on CyD’s
and FAU’s, both bearing 8, to determine whether 8 is
stable toward the reaction conditions. Indeed, it is. Thus,
no 8 was formed from the solid-state photolyses of the 1
IC’s.
F igu r e 1. Structure of cyclodextrin (CyD) cyclic oligosaccha-
rides depicting the O1-C4 R-linkage of D-glucose monomers.
(Newman projection used to highlight inward pointing H3 and
H5 atoms).
The results are in accord with the proposed supramo-
lecular structures of diazirine 1 and its hosts (vide supra).
No azine, di(3-nortricyclanylidene)hydrazine (6), was
formed upon photolysis of the dimeric 1@(R-CyD)2 com-
plex because of a complete encapsulation of the reactive
guest. Bimolecular reaction of the guests within the (1@-
â-CyD)2 dimer should, of course, produce azine 6 by virtue
of their geminated assemblage. Yet, the affinity of
carbene 2 for the O-H bonds present in both CyD’s
predominated, giving O-substituted CyD’s (13a , 13b, 14a ,
(12) (a) Casu, B.; Reggiani, M.; Gallo, G. G.; Vigevani, A. Tetrahe-
dron 1966, 22, 3061-3083. (b) Demarco, P. V.; Thakkar, A. L. J . Chem.
Soc. D 1970, 2-4. (c) MacNicol, D. D. Tetrahedron Lett. 1975, 3325-
3326. (d) Chung, W.-S.; Turro, N. J .; Silver, J .; le Noble, W. J . J . Am.
Chem. Soc. 1990, 112, 1202-1205. (e) Qi, Z. H.; Mak, V.; Diaz, L.;
Grant, D. M.; Chang, C.-j. J . Org. Chem. 1991, 56, 1537-1542. (f)
Salvatierra, D.; J aime, C.; Virgili, A.; Sa´nchez-Ferrando, F. J . Org.
Chem. 1996, 61, 9578-9581.
(13) (a) Alderfer, J . L.; Eliseev, A. V. J . Org. Chem. 1997, 62, 8225-
8226. (b) Ivanov, P. M.; Salvatierra, D.; J aime, C. J . Org. Chem. 1996,
61, 7012-7017.
F igu r e 2. Structure of faujasite zeolite (FAU) depicting 13 Å
diameter supercage and tetrahedral arrangement of 7.4 Å
apertures (cf. diamond fcc structure).
(14) (a) Krois, D.; Brinker, U. H. J . Am. Chem. Soc. 1998, 120,
11627-11632. (b) Bobek, M. M.; Krois, D.; Brinker, U. H. Org. Lett.
2000, 2, 1999-2002.
were analyzed using 1H NMR,12 including 2-D ROESY;13
induced circular dichroism (ICD);14 and microanalysis.
The structures of the CyD IC’s were concluded to be 1@-
(R-CyD)2 and (1@â-CyD)2. This denotes that 1 is sand-
(15) For
a related example employing X-ray diffraction upon a
crystalline diazirine@CyD IC, see: Bobek, M. M.; Giester, G.; Ka¨hlig,
H.; Brinker, U. H. Tetrahedron Lett. 2000, 41, 5663-5667.
(16) The limit of the sequence 1/5, 2/9, 3/13, 4/17, ... n/(5n - (n -
1)) ) n/(4n +1) for infinite n is 0.25.

Notes
J . Org. Chem., Vol. 66, No. 4, 2001 1519
Ta ble 1. Rela tive Yield s (%) of P r od u cts F or m ed u p on P h otolysis of 3-Azin or tr icycla n e (1) in Differ en t Rea ction Med ia
medium
c-C6H12
κa
3
4
6
9
13
14
15
13f
1.3
16
7.0
13/14
2.0
32.7
0.8
1.0
0.9
2.1
trace
14.0
3.8
trace
trace
trace
2.3
trace
trace
trace
48.7
18.7
15.6
16.9
14.2
14.2
6.0
20.0
80.6
69.3
70.4
84.2
3.6
MeOH
2.8
2.0
29
35
w/0.2 M DEFb,c
iPrOH
18.3
6.1
9.9
0.6
0.5
AcOH
R-CyD
â-CyD
1.6
trace
trace
3.4
53
80.0d
52.0d
trace
19.3
trace
N/A
N/A
69
10.0
6.0
11.5
16.3
NaY
e
1.1f
1.1
75.5
a
b
d
Dielectric constant. Diethyl fumarate. c 7 + DEF f scavenger products (10.8% by GC-MS). Sum of 13 and 14. e 13f. f 14f.
and 14b), via innermolecular reactions,17 that were
detected using FAB MS analysis (Table 1).
is, protonation pathway 2f12 should give the charac-
teristic 13/14 ratio in the presence of DEF and in the
absence of ion pairing. It appears that carbene 2 is as
Brønsted basic as its constitutional isomer 5-norbornen-
2-ylidene (17), which has been shown to be protonated
to 12 completely under similar conditions.27,28 The ab-
sence of unsaturated isomers of ether 15 stemming from
5-norbornen-2-ol (14f) may be due to limits of detection.
Alcohol 13f has previously been shown to be stable within
NaY (i.e., no 13ff12).29
Clearly, the presence of azine 6 and di-3-nortricyclyl
ether (15) after photolysis of the 1@NaY FAU IC dem-
onstrates that some bimolecular reactions occurred. The
diffusion of ephemeral carbene 2 within the multicameral
lattice was thus indicated. The principal formation of
3-nortricyclanol (13f) validates that a significant amount
of water still remains inside NaY even after thermal
activation.18
Notwithstanding, the presence of typical H-abstraction
products 3 and 4 may indicate intersystem crossing (isc)
of carbene 2 from the singlet to the triplet state.30 In
CyD’s and cyclohexane, the concomitant oxidation of the
surrounding nonpolar media rendered minor amounts of
didehydro-CyD’s31 (likely via end-on abstraction of H3
within the nonpolar cavity) and bicyclohexyl,32 respec-
tively. The comparatively large molar mass of the CyD
could provide a collisional mechanism for the isc of 2.33
Nevertheless, it is surprising that the triplet state of 2
could be relatively low-lying since angle restraints34
within the polycyclic structure and homoconjugation
between the Walsh orbitals of the cyclopropane ring with
the vacant p-orbital of the carbene (or carbocation)35
center greatly favor the singlet state. Indeed, it is this
interaction of the vacant p-orbital with proximal π-bonds
Since products other than the “sole-reported” enyne 9
were formed within the host vessels, control experi-
ments on 1 in relevant solvents were warranted (Table
1).
1a,19
These trials showed a reluctance of carbene 2 to
undergo intramolecular fragmentation to 9 also in the
condensed phase. The hydrolysis reaction of 2 with trace
amounts of H2O, giving 13f, was evident in each medium.
Yet, the formation of 5-norbornen-2-yl-substituted prod-
ucts 14 in protic media is noteworthy. Unsaturated 14
cannot directly stem from carbene 2 (i.e., no 2f14); it
derives from carbocation 12. Thus, carbene protonation
is indicated (2f12).20 However, the typical product ratio
that is characteristic of nonclassical carbocation 12 (i.e.,
13/14 ) ca. 3.5) was not observed, even in the presence
of diethyl fumarate (DEF).21,22 Thus, the paucity of 14
implies a deviation due to ion pairing of 12 with its
counterion.23
DEF is a potent 1,3-dipolarophile that precludes the
diazonium cation route (7f11f12) by intercepting diazo
compound 7. Indeed, the addition of DEF produced ca.
10% scavenger product, which suggests that some diazo
compound 7 was formed upon irradiation of diazirine 1.24
Barring this route should have reduced the 13/14 ratio
because 12 generated via pathway 10f7f11 gives an
uncharacteristically25 high ratio (13f/14f ) 24).1g,26 That
(24) The putatively formed 1,2-diazacyclopent-1-ene derivative de-
composes to spiro[1,2-bis(ethoxycarbonyl)cyclopropane-3,3′-tricyclo-
[2.2.1.02,6]heptane]: m/z (EI) 219 ([M - OCH2CH3]+, 8), 191 ([M -
C(O)OCH2CH3]+, 100), 163 (11), 145 (7), 125 (11), 117 (32), 97 (13), 91
(15).
(25) Carbocations stemming from diazonium cations, such as 11,
often give spurious product ratios: In Advanced Organic Chemistry,
4th ed.; March, J ., Ed.; Wiley: New York, 1992; p 355.
(26) For the related 5-norbornen-2-yl route, see: Kirmse, W.; Kno¨pfel,
N.; Loosen, K.; Siegfried, R.; Wroblowsky, H.-J . Chem. Ber. 1981, 114,
1187-1191.
(27) Photolysis of 2-azi-5-norbornene is reported to give 13c/14c )
1.9. This ratio is slightly lower than usual for 12 and may also indicate
some ion pairing: Kirmse, W.; Meinert, T. J . Chem. Soc., Chem.
Commun. 1994, 1065-1066.
(28) The 13/14 ratios obtained from carbenes 2 and 17 indicate a
product spread in the direction of the starting compound: Advanced
Organic Chemistry, 4th ed.; March, J ., Ed.; Wiley: New York, 1992; p
328.
(17) (a) Warmuth, R. Chem. Commun. (Cambridge) 1998, 59-60.
(b) Bradley, D. Chem. Br. 1998, 34 (3), 16.
(18) NaY‚253H2O is 26.3% (w/w) H2O; only 22.4 wt % was lost.
(19) After vacuum pyrolysis of salt 10, compounds 3, 4, and the
allenic dimer, 3-[2-(3-cyclopentenyl)ethenylidene]nortricyclane (S1),
were found in addition to 9; see Supporting Information.
(20) (a) Kirmse, W. Adv. Carbene Chem. 2001, 3, in press. (b)
Kirmse, W. Adv. Carbene Chem. 1994, 1, 1-57. (c) Bethell, D.; Newall,
A. R.; Stevens, G.; Whittaker, D. J . Chem. Soc., B 1969, 749-751. (d)
Bethell, D.; Newall, A. R.; Whittaker, D. J . Chem. Soc., B 1971, 23-
31.
(21) (a) Schleyer, P. v. R. J . Am. Chem. Soc. 1958, 80, 1700-1704.
(b) Schmerling, L.; Luvisi, J . P.; Welch, R. W. J . Am. Chem. Soc. 1956,
78, 2819-2821. (c) Roberts, R. M. G. J . Chem. Soc., Perkin Trans. 2
1976, 1183-1190. (d) Cristol, S. J .; Seifert, W. K.; J ohnson, D. W.;
J urale, J . B. J . Am. Chem. Soc. 1962, 84, 3918-3925.
(22) The electron-deficient radical behaves similarly: (a) Davies, D.
I.; Done, J . N.; Hey, D. H. Chem. Commun. (London) 1966, 725-726.
(b) Roberts, J . D.; Trumbull, E. R., J r.; Bennett, W.; Armstrong, R. J .
Am. Chem. Soc. 1950, 72, 3116-3124.
(23) Carbocations stemming from carbenes can give deviant product
ratios due to ion pairing (see ref 20a).
(29) (a) Azbel’, B. I.; Gol’dshleger, N. F.; Isakov, Y. I.; EÄ pel’baum,
E. T.; Yampol’skii, Y. Y.; Minachev, K. M. Bull. Acad. Sci. USSR, Div.
Chem. Sci. 1986, 35, 1122-1125. (b) Azbel’, B. I.; Gol’dshleger, N. F.;
Isakov, Y. I.; EÄ pel’baum, E. T.; Yampol’skii, Y. Y.; Khidekel’, M. L.;
Minachev, K. M. Dokl. Chem. (Transl. of Dokl. Akad. Nauk) 1984, 276,
197-199.
(30) One may postulate that
H atom transfer to excited-state
diazirine 1* leads to diazene, 3-diazenylnortricyclane, that is
a
responsible for the reduction [H].
(31) A carbonyl nfπ* electronic transition (λ ) ca. 280 nm) is
observed with RP HPLC analysis; see Experimental Section.
(32) Wu, G.; J ones, M., J r.; Walton, R.; Lahti, P. M. J . Org. Chem.
1998, 63, 5368-5371.
(33) Wentrup, C. Reactive Molecules; Wiley: New York, 1984; pp
182-183.
(34) Hoffmann, R.; Zeiss, G. D.; Van Dine, G. W. J . Am. Chem. Soc.
1968, 90, 1485-1499.

1520 J . Org. Chem., Vol. 66, No. 4, 2001
Notes
their respective 1,3 C-H insertion products, 8,40 19, and
3. The values of ∆H° clearly show that 2f8 is the least
exothermic and must therefore have the highest Ea.
Indeed, it must be so high that other processes, like
cyclopropylcarbene fragmentation and innermolecular
O-H insertion, happen more readily. Moreover, this
dormant reaction of 2 should also be viewed as a 1,4 C-H
insertion, which is altogether uncommonspresumably
due to improper orbital alignment.2a,41 In particular, this
1,4 C-H insertion would also form a cyclobutane, embed-
ded within 8, that is flat!
Even so, it appears that 2 should also be coerced to
undergo 1,3 (or 1,4) C-H insertion if an appropriate
constraint is imposed. Our experiments show, however,
that this is not the case in the relatively spacious R-CyD
dimer, in â-CyD, or in NaY supercagessall of which also
have many available O-H moieties that intercept the
carbene. Besides O-H insertion, the problem may be that
the fragmentation,42 whose rate likely exceeds that of 1,3
C-H insertion,43 needs less free volume (∆V) for the
unraveling process than we thought. That is, when the
standard equation for the free energy of activation ∆Gq
) ∆Hq - T∆Sq is rewritten as
F igu r e 3. Geometry of carbene 1,3 C-H insertion.
Ta ble 2. P er tin en t In ter a tom ic Dista n ces w ith in
2-Nor bor n a n ylid en e (5), 3-Nor tr icycla n ylid en e (2), a n d
2-Ad a m a n ta n ylid en e (18) Mea su r ed a fter Geom etr y
Op tim iza tion w ith th e AM1 Ha m ilton ia n (cf. F igu r e 3)
r(C1-C3) r(C3-H3) r(C1-H3) θ(C1-C3-H3)
carbene
(Å)
(Å)
(Å)
(deg)
5
2
18
2.411
2.378
2.457
1.115
1.113
1.120
2.571
2.687
2.730
85.3
93.5
102.9
Ta ble 3. Releva n t En th a lp ies (k ca l/m ol) Mea su r ed a fter
Geom etr y Op tim iza tion w ith th e AM1 Ha m ilton ia n
carbene
∆fH°
product
∆fH°
∆H°
2
18
5
+133.2
+54.3
+82.8
8
19
3
+104.3
+9.3
+33.8
-28.9
-45.0
-48.5
Vq
V
∆Gq ) ∆Hq - RT ln
( )
(e.g., Walsh orbitals) that enhances the nucleophilicity
of the carbene.
it becomes obvious that the host vessel must decrease
the volume (Vq) available to the (coarctate) TS to increase
∆Gq and concomitantly inhibit the rate of 2f9. We have
shown, however, that carbene 2 is somewhat more stable
than normal dialkylcarbenes. It undergoes some in-
tramolecular rearrangement to 9 in MeOH, and it forms
some azine 6 in lightly loaded FAU zeolites. Therefore,
we believe that it is still possible to subdue fragmentation
and enhance 1,3 C-H insertion under more confining
conditions.
Theoretical chemistry was engaged to provide informa-
tion about the propensities of carbenes to undergo
exothermic 1,3 C-H insertions. The transformation of 2
into 8 could be geometrically inhibited. The carbene
center C1, C3, and H3 atoms describe a scalene triangle,
whereby cyclopropane ring formation results from incipi-
ent C1-C3 bonding during the closely related TS (Figure
3).
The results of AM1 calculations36 on carbene interme-
diates 5, 2, and 2-adamantanylidene (18) are summarized
in Table 2. These semiempirical SCF methods indicate
the feasibility of 1,3 C-H insertion of carbene 2. Clearly,
both the C1-H3 distance (r) and C1-C3-H3 angle (θ)
values for 2 are intermediary, lying between those of 5
and 18. It has previously been shown that 5 undergoes
1,3 C-H insertion almost exclusively.2 Yet, 18 mostly
undergoes other types of reactions in solution.8a,37 It can,
however, be compelled to undergo 1,3 C-H insertion
giving 2,4-didehydroadamantane (19) either exclusively
in the gas phase38 or appreciably in the supramolecular
phase.8a,b This mixed behavior is noteworthy. So further
calculations were warranted.
In conclusion, we have observed the first inter- and
innermolecular reactions of carbene 2 by photolyzing a
new and suitable precursor, diazirine 1. The constraint
imposed upon carbene 2 within CyD’s and FAU’s was not
enough to prevent its fragmentation into the thermody-
namically favored enyne 9, nor could inclusion enhance
1,3 C-H insertion, forcing 2 into the highly strained 8.
Undoubtedly, the C2-C6 bridge in 2 markedly alters the
chemistry of carbene 2 as compared with that of carbene
5. Bearing in mind that carbenes can be generated within
argon matrixes44 and crystalline media,45 we envision
that the selectivity of carbene 2 will one day be controlled.
Exp er im en ta l Section
The Bell-Evans-Polanyi principle states that there
is a proportionality between the energy of activation (Ea)
and the heat of reaction (∆H°). That is, as a given
reaction type becomes more exothermic, the Ea de-
creases.39 Hence, from the Eyring equation, the rate
(constant) must increase. Table 3 lists the AM1 heats of
formation (∆fH°) of carbenes 2, 18, and 5 with those of
Gen er a l In for m a tion . 3-Nortricyclanone (16) was prepared
according to the literature.11b,21b Hydroxylamine-O-sulfonic acid
(HOSA, 95%, Fluka) was used as purchased. Ag2O was prepared
(40) Experimental ∆fH°(8) ) +81.0 kcal/mol: Steele, W. V. J . Chem.
Thermodyn. 1978, 10, 919-927.
(41) Bradley, G. F.; Evans, W. B. L.; Stevens, I. D. R. J . Chem. Soc.,
Perkin Trans. 2 1977, 1214-1220.
(42) ∆fH°(9) ) +66.3 kcal/mol as calcd by Benson group additivity
method: Benson, S. W.; Cruickshank, F. R.; Golden, D. M.; Haugen,
G. R.; O’Neal, H. E.; Rodgers, A. S.; Shaw, R.; Walsh, R. Chem. Rev.
1969, 69, 279-324.
(35) Advanced Organic Chemistry, 4th ed.; March, J ., Ed.; Wiley:
New York, 1992; p 169.
(36) Austin Model 1: Dewar, M. J . S.; Zoebisch, E. G.; Healy, E. F.;
Stewart, J . J . P. J . Am. Chem. Soc. 1985, 107, 3902-3909.
(37) Isaev, S. D.; Yurchenko, A. G.; Stepanov, F. N.; Kolyada, G.
G.; Novikov, S. S.; Karpenko, N. F. J . Org. Chem. USSR 1973, 9, 745-
748.
(43) Barring quantum mechanical tunneling.
(44) (a) Sheridan, R. S. In Organic Photochemistry and Photobiology;
Horspool, W. M., Ed.; CRC: Boca Raton, FL, 1995; pp 999-1006. (b)
Tomioka, H.; Ozaki, Y.; Koyabu, Y.; Izawa, Y. Tetrahedron Lett. 1982,
23, 1917-1920.
(38) Isaev, S. D.; Yurchenko, A. G.; Stepanov, F. N.; Kolyada, G.
G.; Novikov, S. S. J . Org. Chem. USSR 1973, 9, 436.
(39) Wentrup, C. Reactive Molecules; Wiley: New York, 1984; pp
10-12.
(45) (a) Shin, S. H.; Keating, A. E.; Garcia-Garibay, M. A. J . Am.
Chem. Soc. 1996, 118, 7626-7627. (b) Shin, S. H.; Cizmeciyan, D.;
Keating, A. E.; Khan, S. I.; Garcia-Garibay, M. A. J . Am. Chem. Soc.
1997, 119, 1859-1868.

Notes
J . Org. Chem., Vol. 66, No. 4, 2001 1521
immediately prior to use.46 R-CyD and â-CyD were recrystallized
from H2O and found to be 90.0% (w/w) and 86.5% (w/w),
respectively, by microanalysis. NaY and bicyclohexyl were
purchased from Aldrich. Photolyses were performed using a
Heraeus TQ 718 Z4 700-W medium-pressure Hg-arc lamp doped
with FeI2 (λmax ) 370 nm) at Tsample ) 15 °C. Solution photolyses
of 1 (concn ) 0.02 M) were performed in Schlenk tubes after
three freeze-pump-thaw cycles with argon purging. FT NMR
spectra were recorded on a Bruker Avance DPX-250 spectrom-
eter (Bo ) 5.875 T) at the following Larmor frequencies: νo(1H)
) 250.1 MHz and νo(13C) ) 62.9 MHz. 2-D ROESY spectra of
the dilute D2O solutions of 1@(R-CyD)2 and (1@â-CyD)2 were
obtained using 0.60 and 0.45 s mixing times, respectively, with
solvent peak presaturation. IR absorption spectra were recorded
on a Perkin-Elmer 1600 FT IR spectrometer by applying samples
as neat liquids onto a Si wafer or by pressing dilute KBr pellets.
UV/vis absorption spectra were recorded on a Perkin-Elmer
Lambda 7 UV/vis spectrometer. CD spectra were obtained using
a CD 6 circular dichrograph (I.S.A. J obin Yvon) spectrometer.
Analytical GC analyses were conducted using a Fisons 8000
series GC instrument outfitted with a 30 m poly(dimethylsilox-
ane) capillary column (Perkin-Elmer, PE-1, 0.32 mm i.d., and
0.25 µm film-thickness) and a flame-ionization detector. The
following conditions and temperature program were used: Toven,i
) 50 °C (5 min), ramp ) +10 °C/min, Toven,f ) 230 °C (7 min),
Tinjector ) 185 °C, TFID ) 260 °C, and flow ) 2.1 (mL He)/min.
Preparative GC was performed using a Varian Aerograph model
920 instrument equipped with a 3.05 m Al column (6.4 mm i.d.)
packed with 20% QF1 on Chromosorb (80-100 mesh, NAW) and
a thermal conductivity detector. The following isothermal condi-
tions were used: Toven ) 100 °C, Tinjector ) 200 °C, TTCD ) 200
°C, and flow ) 76 (mL He)/min. The effluent was condensed
using a CO2(s)/iPrOH trap. GC-MS analyses were conducted
using a Hewlett-Packard 6890 series GC outfitted with a 30 m
poly(methylphenylsiloxane) capillary column (Hewlett-Packard,
HP-5MS {95% diMe and 5% diPh}, 0.25 mm i.d., and 0.25 µm
film-thickness) and a Hewlett-Packard 5973 MSD; a Hewlett-
Packard 59864B ionization gauge controller was used for chemi-
cal ionization studies. The following GC conditions and temper-
ature programs were used: Toven,i ) 80 °C (7 min), ramp ) +10
°C/min, Toven,f ) 270 °C (5 min), Tinjector ) 200 °C, and initial
flow ) 0.8 (mL He)/min. Microanalysis was employed to deter-
mine the guest@host stoichiometry of the CyD IC’s as well as
their water content. Analytical RP HPLC was performed using
MeOH.48 The mixture was refluxed at ca. -33 °C for 1.5 h before
addition of the aminating agent. Meanwhile, HOSA (6.071 g,
51 mmol) was dissolved in 50 mL of anhydrous MeOH and sealed
in an Erlenmeyer flask with a rubber septum. After cooling this
solution in an ice bath, the stirring speed was increased and
aliquots of this solution were injected via syringe every 10 min
according to the following schedule: 6 × 3.33 mL during the
first hour, 6 × 2.50 mL during the second hour, 6 × 1.67 mL
during the third hour, and 6 × 0.83 mL during the fourth hour,
by which time the reaction T had climbed to -28 °C. The stirring
speed was reduced and the NH3(g) was allowed to slowly
evaporate overnight in the hood. Both ends of the cool mixture
were stoppered, and the remaining NH3 and MeOH were rotary-
evaporated using water aspiration. The white residue was
transferred into a sinter funnel (Por. 4) and triturated with CH2-
Cl2 (6 × 50 mL). Each portion was suction-filtered into a
receiving flask. The combined, faintly purple filtrates were
poured into a 500 mL r.b. flask, and the solvent was rotary-
evaporated. The residue was dissolved in Et2O (30 mL) and
transferred to a loosely stoppered 50 mL r.b. flask that was
equipped with a stirbar and submerged in a room-temperature
water bath. Overhead lighting was dimmed. The putative
diaziridine49 was oxidized with freshly prepared Ag2O by rapidly
stirring overnight.50 The mixture was dried with anhydrous Na2-
SO4, suction-filtered (Por. 4 sinter funnel),51 and rotary-
evaporated, and the residual oil was chromatographed (silica
gel 60, 230-400 mesh) using pentane as eluent. The nonpolar
diazirine eluted first, giving 0.356 g, 6% yield of a colorless,
odorous liquid after careful rotary evaporation:52 δH/ppm (CDCl3)
0.27 (1 H, td J 5.3, J 1.3), 0.93-0.97 (1 H, m), 1.41 (2 H, dm J
10.3), 1.49 (2 H, dm J 5.3), 1.92 (2 H, dm J 10.3); δC/ppm (CDCl3)
11.3 (d J 179), 13.0 (d J 177), 32.0 (t J 134), 33.0 (d J 147), 42.7
(s); νjmax/cm-1 (neat) 3071, 3005, 2947, 2871, 1567, 1446, 1290,
1239, 936, 821, 787; λmax/nm (pentane) 354, 373; m/z (CI, CH4)53
149 ([M + C2H5]+, 1), 121 ([M + H]+, 49), 108 (13), 104 (36), 94
(31), 93 (64), 92 (19), 91 (100), 79 (23), 67 (9).
4-Eth yn ylcyclop en ten e (9). CAUTION! Injection of diaz-
irine 1 (60 mg, 0.12 mL of CDCl3) into the preparative GC
afforded the malodorous enyne in 91% yield: δH/ppm (CDCl3)
2.04 (1 H, d J 2.5), 2.38-2.54 (2 H, m), 2.62-2.78 (2 H, m), 2.93-
3.08 (1 H, m), 5.64-5.72 (2 H, m); δC/ppm (CDCl3) 27.6 (d J 132),
40.2 (t J 130), 67.4 (d J 248), 89.0 (s), 129.3 (d J 168); νjmax/cm-1
(neat) 3307, 3061, 2940, 2856, 2118, 1615; m/z (EI) 92 (M+, 28),
91 ([M - H]+, 100), 89 (3), 66 (3), 65 (10), 63 (6).
P r ep a r a tion a n d P h otolysis of 1@(r-CyD)2 a n d (1@â-
CyD)2. Filtered solutions of R-CyD (0.811 g, 0.750 mmol, 12.0
mL of H2O) and â-CyD (0.492 g, 0.375 mmol, 36.5 mL of H2O)
were rapidly stirred in a room-temperature water bath under
the exclusion of light. Neat diazirine 1 (30 mg, 0.25 mmol) was
injected into each solution and stirred overnight. The white
suspensions were transferred to tared centrifuge tubes and
centrifuged (2.2K rpm, T ) 18 °C, 25 min), and the supernatants
were decanted. Each precipitate was triturated with 3 mL of
H2O and recentrifuged. After decanting the washings, the
samples were placed in a vacuum desiccator, preevacuated by a
diaphragm pump, and evacuated by a high-vacuum oil pump to
ca. 0.2 mmHg for 4 h, giving 0.331 g of R-CyD IC (Found: C,
42.46; H, 6.58; N, 0.97, corresponding to 1@2.6R-CyD‚11H2O,
46% yield) and 0.180 g of â-CyD IC (Found: C, 44.00; H, 6.48;
N, 1.88, corresponding to 1@1.1â-CyD‚4H2O, 50% yield). The 2-D
ROESY spectrum of the R-CyD IC showed cross-peaks between
all protons of 1 with only H3 of R-CyD; that of the â-CyD IC
a
Hewlett-Packard HP 1090 liquid chromatograph with a
Hewlett-Packard 35900E interface, equipped with a Nucleosil
300-5 C8 5 µm column (290 × 4 mm, FZ Seibersdorf, Austria).
Isocratic elution giving a 70% H2O and 30% MeOH mixture was
employed at 0.5 mL/min. Product signals were observed using
an UV detector (λ ) 211, 281 nm) and a HP 1047A RI detector,
consecutively, and compared with those from R-CyD and â-CyD
standards. FAB MS assays were performed on a Finnigan MAT
900 spectrometer by bombarding the photolyzed CyD IC’s, in a
1-thioglycerol matrix, with a 20 keV beam of Cs atoms at 70 °C.
3-Azin or tr icycla n e (1). CAUTION! Within an efficient fume
hood, 100 mL of NH3(l) were condensed by passing NH3(g) through
a column of KOH(s) drying agent, then through the rubber
septum of a dry, graduated 250 mL Schlenk flask that was
submerged in a CO2(s)/iPrOH bath.47 A hand bellows and a large-
bore double-ended needle were used to cannulate the NH3(l)
through the rubber septum of a 500 mL three-necked round-
bottom (r.b.) flask that was also equipped with a low-T ther-
mometer, a large stirbar, and a 1 L suspended condenser, or
coldfinger, which was filled (and periodically refilled) with
pulverized dry ice and whose outlet included a silicone oil
bubbler. With moderate stirring, neat ketone 16 (5.407 g, 50
mmol) was slowly injected via syringe and rinsed with 1 mL of
(48) A peach color develops that is soon followed by the gradual
formation of a white precipitate.
(49) 3-Hydrazinortricyclane: νjmax/cm-1 (KBr) 3204; m/z (EI) 122
(M+, 20), 121 ([M - H]+, 36), 107 ([M - NH]+, 71), 106 (61), 104 (9),
95 (33), 91 (49), 80 (60), 79 (100), 77 (55), 67 (28), 66 (29).
(50) Although expected, a silver mirror may not form due to a low
yield.
(46) Silver oxide: (wear gloves) 16.5 mL of 2.0 M NaOH was diluted
to 45 mL, then slowly poured into a stirred solution of AgNO3 (5.096
g, 30 mmol) in 45 mL of H2O. The brown precipitate was suction-
filtered (Por. 4 sinter funnel), washed with H2O until the drippings
were of neutral pH, and rinsed with acetone and then Et2O, to dry it,
yielding 3.430 g, 14.8 mmol.
(51) The silver residues can be digested by 50% (w/w) aqueous
HNO3.
(52) Diazirine 1 may be preserved for several weeks in the freezer
(-22 °C).
(53) For a related MS analysis of 3H-diazirines using isobutane as
the reagent gas, see: Isaev, S. D.; Karpenko, N. F.; Yurchenko, A. G.;
Vodicˇka, L.; Kadentsev, V. I.; Zacharˇ, P. Collect. Czech. Chem.
Commun. 1989, 54, 691-698.
(47) A slowly inflating balloon attached to the flask outlet indicates
that a slight positive pressure is being maintained.

1522 J . Org. Chem., Vol. 66, No. 4, 2001
Notes
showed cross-peaks between protons of 1 with H3 and H5 of
â-CyD. Next, the CyD IC’s (50 mg each) were transferred to
Schlenk tubes, sealed with rubber septa, and alternately evacu-
ated and purged with argon three times. The CyD IC’s were
photolyzed for 1 day. A 5 mg portion of each photolyzed CyD IC
was set aside for NMR (DMSO-d6) and FAB MS analyses. 13a
and 14a : m/z (-νe FAB, thioglycerol) 1063.5 ([M - H]-). 13b
and 14b: m/z (-νe FAB, thioglycerol) 1225.3 ([M - H]-).54 The
remaining samples were each dissolved in 100 mL of H2O and
continuously extracted overnight with 100 mL of refluxing
anhydrous CH2Cl2, which was subsequently analyzed by GC.
Each aqueous layer was collected and subjected to rotary
evaporation (T ) 50 °C) to recover the CyD’s. Hence, analytical
RP HPLC was also employed to observe and quantify the
modified CyD’s.
P r ep a r a tion a n d P h otolysis of 1@Na Y. Zeolite NaY‚
253H2O (0.451 g) was dried overnight according to the following
oven program: 1 h ramp until Toven ) 100 °C (1 h), 2 h ramp
until Toven ) 500 °C (12 h), reduce to Toven ) 150 °C (hold).55 It
was then cooled to room temperature in an anhydrous CaCl2
desiccator. The sample was quickly transferred into a dry,
stirbar-containing, tared centrifuge tube with rubber septum and
weighed, giving 0.350 g of NaY‚xH2O.56 Diazirine 1 (6.6 mg, 55
µmol) was dissolved in 4.6 mL of anhydrous pentane,57 a 1.0 µL
aliquot was analyzed by GC (Tinjector ) 140 °C), and the rest was
poured into the centrifuge tube, which was quickly resealed. The
suspension was slowly stirred for 3 h in a room-temperature
water bath. After removing the stirbar, the sample was centri-
fuged (2.2K rpm, T ) 18 °C, 20 min) and the supernatant was
decanted. Analysis by GC showed that no 1 remained in solution.
The FAU IC was triturated with 2 mL of anhydrous pentane
and recentrifuged. After decanting the washing, the FAU IC was
placed in a vacuum desiccator, preevacuated by a diaphragm
pump, and evacuated by a high-vacuum oil pump to ca. 0.2
mmHg for 15 min. The sample was slowly repressurized using
an argon-filled balloon and resealed. The FAU IC was photolyzed
for 2 days with constant rotation. The photolyzed sample was
transferred to a Soxhlet-type extractor and continuously ex-
tracted overnight with 40 mL of refluxing anhydrous CH2Cl2,
which was subsequently analyzed by GC.
Ack n ow led gm en t . We thank the Fonds zur
Fo¨rderung der wissenschaftlichen Forschung in O¨ ster-
reich (Project P12533-CHE) for financial support and
both Cerestar USA, Inc., and Wacker Chemie, Germany,
for providing the cyclodextrins used in this study. We
are also grateful to Dr. D. Krois and Ing. U. Haslinger
for their assistance. Helpful consultations with Prof. W.
Kirmse, Ruhr-Universita¨t Bochum, Germany, Prof. B.
K. Carpenter, Cornell University, U.S.A., and H. W. G.
van Herwijnen, Universita¨t Wien, Austria, are greatly
appreciated.
(54) Also observed m/z (-νe FAB, thioglycerol) 1317.5 ([M - H]-).
This corresponds to an innermolecular insertion product of two
carbenes 2 with one â-CyD, which may be expected from dimeric (1@â-
CyD)2.
(55) Slowly heating the FAU prevents the possible formation of
Lewis acidic sites within the zeolite lattice that might decompose a
3H-diazirine: van Herwijnen, H. W. G., Universita¨t Wien, personal
communication, 1999.
Su p p or tin g In for m a tion Ava ila ble: Vacuum pyrolysis
of 10. Z-Matrixes for 2, 3, 5, 8, 18, and 19 with computed total
energies. 2-D ROESY spectra of 1@(R-CyD)2 and (1@â-CyD)2.
ICD spectrum of 1@(R-CyD)2. Formula for 13/14 ratio as a
function of the extent of ion pairing with accompanying graph.
This material is available free of charge via the Internet at
http://pubs.acs.org
(56) x ) ca. 38; see ref 18.
(57) s ) {(17319.66 g/mol NaY‚253H2O)(1 mol NaY‚253H2O)(55
µmol 1)}/{(0.451 g)(8 mol supercage)} ) 0.26 1/supercage.
J O005713E