Tributyltin Hydride-Mediated Free-Radical Cyclization of Allene-Tethered Oxime Ethers and Hydrazones

Article abstract of DOI:10.1021/jo962225r

In this work, we have shown that the tributyltin hydride-mediated cycloisomerization of allenetethered oxime ethers or hydrazones is a convenient method for the preparation of (vinylstannyl)-cyclopentylamine derivatives in terms of simplicity and chemical yields. As a result, the first and detailed analysis of the tributyltin hydride-mediated free-radical cyclization of alkyl-substituted allene-tethered oxime ethers and hydrazones is reported. The site-directed intermolecular attack of the tributyltin radical at the allene moiety and the final size of the ring after cyclization depends on the type of substitution in the substrate. Some general trends can be observed: (1) In crowded substrates having full substitution at Cβ or at the terminal-trigonal carbon, the steric hindrance favors attack at the digonal carbon. (2) When different positions in the allene are free for attack, the kinetically more favored irreversible mode of cyclizations (5-exo > 6-exo > 6-endo) determines the ratio of isomers or the final size of the ring. Finally, after acid hydrolysis of the vinyltin products, the resulting O-methyl- or O-benzyl(hydroxylamino)cycloalkanes have been obtained in good yield.

Full text of DOI:10.1021/jo962225r

1202
J . Org. Chem. 1997, 62, 1202-1209
Articles
Tr ibu tyltin Hyd r id e-Med ia ted F r ee-Ra d ica l Cycliza tion of
Allen e-Teth er ed Oxim e Eth er s a n d Hyd r a zon es
J ose´ Marco-Contelles,*,† Genevie`ve Balme,‡ Didier Bouyssi,‡ Christine Destabel,†
Christiane D. Henriet-Bernard,§ J . Grimaldi,§ and J acques M. Hatem*,§
Instituto de Quı´mica Orga´nica General, (CSIC), J uan de la Cierva, 3, 28006-Madrid, Spain,
Laboratoire de Chimie Organique 1, associe´ au CNRS, Universite´ Claude Bernard, ESCIL,
43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France, and Laboratoire de Chimie Organique de
Synthe´se, Universite´ de Provence, Case 541, F-13397 Marseille Ce´dex 13, France
Received November 27, 1996X
In this work, we have shown that the tributyltin hydride-mediated cycloisomerization of allene-
tethered oxime ethers or hydrazones is a convenient method for the preparation of (vinylstannyl)-
cyclopentylamine derivatives in terms of simplicity and chemical yields. As a result, the first and
detailed analysis of the tributyltin hydride-mediated free-radical cyclization of alkyl-substituted
allene-tethered oxime ethers and hydrazones is reported. The site-directed intermolecular attack
of the tributyltin radical at the allene moiety and the final size of the ring after cyclization depends
on the type of substitution in the substrate. Some general trends can be observed: (1) In crowded
substrates having full substitution at Câ or at the terminal-trigonal carbon, the steric hindrance
favors attack at the digonal carbon. (2) When different positions in the allene are free for attack,
the kinetically more favored irreversible mode of cyclizations (5-exo > 6-exo > 6-endo) determines
the ratio of isomers or the final size of the ring. Finally, after acid hydrolysis of the vinyltin products,
the resulting O-methyl- or O-benzyl(hydroxylamino)cycloalkanes have been obtained in good yield.
In tr od u ction
allenic-tethered-oxime ethers.5a,b These studies have
largely contributed to establish the synthetic usefulness
of this strategy and enlarge the basic knowledge of these
free-radical cyclizations.
The pioneer studies described by some of us in the
carbocyclization of allenic-tethered oxime ethers deserve
particular mention.5 In 1992, nothing was known about
this reaction and its synthetic potential. In this paper,
we now describe in full the first results obtained in the
free-radical cycloisomerization of allene-tethered oxime
ethers and complementary studies in analogous racemic
or enantiomerically pure allene-tethered hydrazones.
Free-radical inter- and intramolecular carbon-carbon
bond-forming reactions are of paramount importance in
organic synthesis.1 In recent years, densely functional-
ized carbocycles have been efficiently prepared from
conveniently functionalized precursors using free-radical-
based methodologies.1c There has also been an increasing
number of papers dealing with radical additions to
N-containing multiple bonds.2 Carbocyclization of radi-
cals onto CdN bonds has been most studied in oxime
ethers3 and hydrazones.4 Our teams in Marseille5 and
Madrid6 have been particularly active in this topic, and
in recent years, we have described extensively the
tributyltin hydride-mediated synthesis of highly func-
tionalized, chiral complex aminocyclitols or cyclopentyl/
cyclohexylamine derivatives using halogeno-tethered-
oxime ethers,6a-g carbonyl-tethered-oxime ethers,6j and
Resu lts a n d Discu ssion
The particular structure and functionality of these
allene-containing molecules raises several interesting
problems. First, we have to consider that in the revers-
ible intermolecular addition of the tributyltin species to
the allene three positions are available for attack (C-1,
† Instituto de Qu´ımica Orga´nica General.
‡ Universite´ Claude Bernard.
§ Universite´ de Provence.
X Abstract published in Advance ACS Abstracts, February 1, 1997.
(1) (a) Giese, B. Radicals in Organic Synthesis: Formation of
Carbon-Carbon Bonds; Pergamon Press: New York, 1986. (b) Curran,
D. P. Synthesis 1988, 417-439, 489-513. (c) J asperse, C. P.; Curran,
D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237-1286. (d) Motherwell,
W. B.; Crich, D. Free Radical Chain Reactions in Organic Synthesis;
Academic Press: London, 1991.
(2) Bowman, W. R.; Stephenson, P. T.; Terrett, N. K.; Young, A. R.
Tetrahedron 1995, 51, 7959-7980 and references cited therein.
(3) Booth, S. E.; J enkins, P. R.; Swain, C. J .; Sweeney, J . B. J . Chem.
Soc., Perkin Trans. 1 1994, 3499 and references cited therein.
(4) Sturino, C. F.; Fallis, A. G. J . Org. Chem. 1994, 59, 6514-6516.
(5) (a) Hatem, J .; Henriet-Bernard, C.; Grimaldi, J .; Maurin, R.
Tetrahedron Lett. 1992, 33, 1057-1058. (b) Henriet-Bernard, C.;
Grimaldi, J .; Hatem, J . Tetrahedron Lett. 1994, 35, 3699-3702. (c)
El Gueddari, F.; Grimaldi, J .; Hatem, J . Tetrahedron Lett. 1995, 36,
6685-6688.
(6) (a) Marco-Contelles, J .; Mart´ınez, L.; Mart´ınez-Grau, A.; Pozuelo,
C.; J imeno, M. L. Tetrahedron Lett. 1991, 32, 6437-6440. (b) Marco-
Contelles, J .; Pozuelo, C.; J imeno, M. L.; Mart´ınez, L.; Mart´ınez-Grau,
A. J . Org. Chem. 1992, 57, 2625-2631. (c) Marco-Contelles, J .;
Sa´nchez, B.; Pozuelo, C. Nat. Prod. Lett. 1992, 1, 167-170. (d) Marco-
Contelles, J .; Sa´nchez, B. J . Org. Chem. 1993, 58, 4293-4297. (e)
Marco-Contelles, J .; Bernabe´, M.; Ayala, D.; Sa´nchez, B. J . Org. Chem.
1994, 59, 1234-1235. (f) Marco-Contelles, J .; Sa´nchez, B.; Pozuelo,
C. Tetrahedron: Asymmetry 1992, 3, 689-692. (g) Marco-Contelles,
J .; Mart´ınez, L.; Mart´ınez-Grau, A. Tetrahedron: Asymmetry 1991, 2,
961-964. (h) Marco-Contelles, J .; Destabel, C.; Chiara, J . L.; Bernabe´,
M. Tetrahedron: Asymmetry 1995, 6, 1547-1550. (i) Marco-Contelles,
J .; Destabel, C.; Gallego, P. J . Carbohydr. Chem. 1995, 14, 1343-1352.
(j) Chiara, J . L.; Marco-Contelles, J .; Khiar, N.; Gallego, P.; Destabel,
C.; Bernabe´, M. J . Org. Chem. 1995, 60, 6010-6011. (k) Marco-
Contelles, J .; Destabel, C.; Gallego, P.; Bernabe´, M. J . Org. Chem. 1996,
61, 1354-1362.
S0022-3263(96)02225-6 CCC: $14.00 © 1997 American Chemical Society

Cyclization of Allene-Tethered Oxime Ethers
J . Org. Chem., Vol. 62, No. 5, 1997 1203
Sch em e 1. Syn th etic Rou tes to Ra d ica l
C-2, C-3) (eq 1); second, we also have to consider the
different reactivity of the resulting vinylic versus allylic
radicals and the allyl isomerization in each of these
species; and third, these radicals species have several
options possible for the intramolecular cyclization (5-exo/
6-exo/6-endo). Fortunately, in oxime ethers and hydra-
zones the endo-intramolecular additions are disfavored,
and this simplifies matters with regard to possible
products.2
P r ecu r sor s 3-12
having a proline motive as the chiral inductor. In
summary, with this large array of radical precursors, we
wanted to analyze the effect of the number of carbons
connecting the tether and the allene, the effect of the
alkyl substitution at the different positions, and the type
of CdN multiple bond used as radical acceptor dur-
ing the tributyltin radical attack and subsequent cycliza-
tion.
A careful survey of the literature has shown that
reports on the intermolecular free-radical addition of
heteroatom-centered radicals to allenes are scarce, but
documented: i.e., photochemical addition of disulfides
and diselenides7 and palladium-catalyzed hydrostanna-
tion.8 From these studies, it was soon clear that the
simple tributyltin hydride + AIBN addition to allenes
was, surprisingly, almost unexplored, and in addition,
the reaction of the tin species, catalyzed by palladium
complexes, to allenes was poorly regioselective. In sum-
mary, a systematic structure-reactivity analysis would
be necessary to determine the factors and parameters
governing this process.
Syn th esis of th e Ra d ica l P r ecu r sor s. Then, with
this in mind we have designed and prepared the radical
precursors 1-12. Compounds 1 and 2 are δ- and γ-
allenic O-benzyloxime ethers, respectively. Compounds
3-6 are â-allenic O-methyloxime ethers, derived from
aldehydes, having different alkyl substitution at the
R-carbon or at the terminal allenyl carbon. Compounds
7-11 are â-allenic N,N-dimethylhydrazones, derived
from ketones or aldehydes, having different alkyl sub-
stitution at the terminal allenyl carbon. Compound 12
is a chiral hydrazone with a similar substitution pattern,
Compounds 1 and 29a were prepared by routine ma-
nipulation (Supporting Information). Compounds 3-12
were prepared as shown in Scheme 1 by standard or
known synthetic methodologies (see the Supporting
Information). Oxime ethers 3-5 and hydrazones 7-10
and 12 have been isolated only as pure E isomers, as we
could determine by 1H NMR analysis, measuring the
chemical shift for the proton in the CdN multiple bond
(around 7.2 ppm in oxime ethers and 6.5 ppm in hydra-
zones). On the contrary, precursor 6 was isolated as a
(7) Ogawa, A.; Yokoyama, K.; Yokoyama, H.; Sekiguchi, M.; Kambe,
N.; Sonoda, N. Tetrahedron Lett. 1990, 31, 5931-5934.
(8) (a) Mitchell, T. N.; Schneider, U. J . Organomet. Chem. 1991, 405,
195-199. (b) Mitchell, T. N.; Schneider, U. J . Organomet. Chem. 1991,
407, 319-327. (c) Koerber, K.; Gore´, J .; Vate´le, M. Tetrahedron Lett.
1991, 32, 1187-1190. The stannylcupration of allenes has also been
described: (d) Barbero, A.; Cuadrado, P.; Fleming, I.; Gonza´lez, A. M.;
Pulido, F. J . J . Chem. Soc., Perkin Trans. 1 1992, 327-331.
(9) (a) J .M.-C. thanks Dr. Manuel Bernabe´ for 1H NMR spectroscopic
analyses of compounds 1 and 2. (b) J .M.-H. thanks Dr. M. Pierrot and
Dr. H. Alilou (Centre de Cristallographie, Faculte´ de St. J e´roˆme,
Marseille) for the X-ray structure determination of compound 25d .

1204 J . Org. Chem., Vol. 62, No. 5, 1997
Marco-Contelles et al.
Sch em e 2. F r ee-Ra d ica l Cycliza tion of P r ecu r sor
1
Sch em e 3. F r ee-Ra d ica l Cycliza tion of P r ecu r sor
2
Sch em e 4. Mech a n ism for th e F r ee-Ra d ica l
Cycliza tion of Ra d ica l P r ecu r sor 1
mixture (1:1) of E and Z isomers (see the Supporting
Information).
F r ee-Ra d ica l Cycliza tion of th e Ra d ica l P r ecu r -
sor s. (A) Allen e-Tet h er ed Oxim e E t h er s. (A1) δ-
Isom er s. When compound 1 (obtained as an inseparable
mixture of E/Z isomers in 7.2:1 ratio)9a was treated with
tributyltin hydride in the presence of triethylborane,10
in toluene at 70 °C, a mixture of tin-derived adducts 17
was isolated in 72% yield and without further analysis
was submitted to acid hydrolysis with HCl/EtOH.11
Under these conditions, we were able to separate and
isolate compounds 18 (45%) and 19 (11%) in reasonable
yield (Scheme 2). O-Benzylhydroxylamine 19 appears as
a single product (1H NMR analysis) whose stereochem-
istry could not be established.
(A2) γ-Isom er s. Compound 2 (obtained as an insepa-
rable mixture of E/Z isomers in 3:1 ratio),9a when submit-
ted to the same experimental conditions, afforded the
allyltin intermediate 20 that after acid hydrolysis gave
the cyclopentylamine derivative 21 as the only detected
and isolated compound (Scheme 3).
Compounds 18 (Scheme 2) and 21 (Scheme 3) obviously
arise from the simultaneous allylic isomerization of the
corresponding allyltin intermediates 17A and 20, respec-
tively, to give the most stable exo methylene product.
This type of isomerization under these experimental
conditions is very well known.12 We can assume that the
ratio of isomers 18/19 represents very exactly the true
ratio of the tributyltin intermediates, since compound 19
(Scheme 2) comes from simple acid hydrolysis of the
vinyltin adduct 17B.
In Scheme 4 we present a hypothetical mechanism for
the observed results in the cyclization of radical precur-
sors 1. As there is no substitution in the δ position, the
attack at the carbon (C-1) is possible, but this is less
sterically favored than the attack at C-2 (digonal) or at
C-3 (trigonal). From the experimental results it is clear
that the formation of major compound 18 requires
preferential attack of the tributyltin radical at C-3 over
C-2 in a ratio 4:1. This can be explained as follows: the
tributyltin radical reaction with the allene is likely
reversible; in addition, the tributyltin radical attacks the
sp2 carbon instead of the sp carbon, where the electronic
interaction is more repulsive. Each of the radical species
cyclizes in a 5-exo or 6-exo mode to the corresponding
radical, which on reaction with tributyltin hydride traps
hydrogen to give the mixture 17, reinitiating the free-
radical chain reaction. These results are also in good
agreement with the reported results for intermolecular
reactions with unsubstituted allenes.8
In the carbocyclization of compound 2 only attack at
the terminal (C-3) or at the C-1 carbons is observed. This
leads to a vinyl radical species that after 5-exo-trig free-
radical cyclization gives an allyltin derivative that after
acid hydrolysis yields the observed compound 21. Inter-
estingly, the attack at the digonal carbon C-2, which
would have given allylic positioned radicals, is not
detected; one of these allylic species would have cyclized
in an unusual 4-exo13 mode and the other in a favorable
6-exo process, but much less favored than the 5-exo mode
that leads finally to compound 21 (Scheme 5).
In summary, attack at sp2 carbons is always electroni-
cally exclusive or favored; in these cases attack at the sp
carbon proceeds if the resulting reactive allylic radical
(10) Nozaki, K.; Oshima, K.; Utimoto, K. J . Am. Chem. Soc. 1987,
109, 2547.
(11) Ardisson, J .; Fe´re´zou, J . P.; J ulia, M.; Pancrazi, A. Tetrahedron
Lett. 1987, 28, 2001.
(12) Pereyre, M.; Quintard, J . P.; Rahm, A. Tin in Organic Synthesis;
Butterworths: London, 1986.
(13) (a) Park, S. U.; Varick, T. R.; Newcomb, M. Tetrahedron Lett.
1990, 31, 2975-2978. (b) J ung, M. E.; Trifunovich, I. D.; Lensen, N.
Tetrahedron Lett. 1992, 33, 6719-6722.

Cyclization of Allene-Tethered Oxime Ethers
J . Org. Chem., Vol. 62, No. 5, 1997 1205
Sch em e 5. Mech a n ism for th e F r ee-Ra d ica l
Cycliza tion of P r ecu r sor 2
Sch em e 7. Mech a n ism for th e F r ee-Ra d ica l
Cycliza tion of Ra d ica l P r ecu r sor s 4 a n d 5
Sch em e 8. F r ee-Ra d ica l Cycliza tion of Ra d ica l
P r ecu r sor s 7-9
Sch em e 6. F r ee-Ra d ica l Cycliza tion of Ra d ica l
P r ecu r sor s 3-6
ment of the relative stereochemistry at the newly formed
stereocenters in these compounds has been established
1
by detailed H and 13C NMR analysis. In both cases, the
major isomer always has the methyl group and the amino
function in cis relative orientation. Final acid hydrolysis
in strong conditions (HCl/Et2O; note that other standard
conditions for protodestannylations were unsuccessful:
AcOH, SiO2, BuLi)11 gave the destannylated compounds
23a -d in good yield (Scheme 6).
The formation of the major products during the tri-
butyltin hydride reaction with the radical precursors 4
and 5 can be explained according to Beckwith’s guide-
lines,14 applied to 1,4,4′-trialkyl-substituted 3,5-hexa-
dienyl radicals. Then, we assumed that, in the early
transition state, the favored radical species is in a
pseudochair-like conformation with most of the substit-
uents in the preferred pseudoequatorial orientation.
According to this model, the radical derived from 4 and
5 gave in both cases major isomers where the methyl
group on C5 and the amino function are cis (Scheme 7).
(B) Allen e-Tet h er ed N,N-Dim et h ylh yd r a zon es
7-11. Radical precursors 7-9, when submitted to the
same experimental conditions, gave the corresponding
vinyltin hydrazines 24a -c in good yield (Scheme 8). The
cyclization of 8 (f 24b: 81/19) and 9 (f 24c: 60/40) is
diastereoselective; the major product is, in both cases,
the one that has the methyl group and the amino function
can undergo a very kinetically 5-exo-favored mode of
cyclization.
(A3) â-Isom er s. The following radical precursors
tested were the allene-tethered oxime ethers 3-6. In
these substrates, the terminal position C-3 and the â
carbon are dialkyl substituted (except for the oxime ether
6). Obviously, with this substitution pattern the tri-
butylstannyl radical attack at C-1 and C-3 was precluded
by strong steric interactions; as a consequence, only the
attack at C-2 was possible. The experimental results
largely confirmed this assumption (Scheme 6).
With the experimental conditions (HSnBu3, AIBN),
compounds 3-6 gave the vinyltin derivatives 22a -d in
moderate to good yield; carbocycles 22b and 22c have
been isolated as inseparable mixtures of isomers in 66/
34 and 88/12 ratios, respectively. These values have been
1
obtained by H NMR spectrum integration. The assign-
(14) Beckwith, A. L. J .; Schiesser, C. H. Tetrahedron 1985, 41, 3925.

1206 J . Org. Chem., Vol. 62, No. 5, 1997
Marco-Contelles et al.
Sch em e 10. P ossible Mech a n ism for th e
Tin -Med ia ted Ra d ica l Rea ction of P r ecu r sor s 10
a n d 11
Sch em e 9. F r ee-Ra d ica l Cycliza tion of Ra d ica l
P r ecu r sor s 10 a n d 11
in the cis orientation.15 This is also in agreement with
the results obtained for the cyclization of the similar
oxime ethers previously described (see above) and can
be explained according to the same stereoelectronic
arguments as shown in Scheme 7. However, under the
same experimental conditions, radical precursors 10 and
11 gave different results, and the new product (25d or
25e) was detected (Scheme 9). Hydrazone 25e has been
isolated as a mixture of E and Z isomers, in a 7/3 ratio,
respectively, that we were unable to separate. The
structure of product 25d (only the E product has been
detected) has been conclusively determined by X-ray
analysis.9b
The formation of compounds of type 25 was unex-
pected, and in Scheme 10 we show a tentative mecha-
nism. The cyclopentene derivatives 24 originate from the
initial attack of the tin radical on the digonal carbon of
the allene. The alkyl radical A binds to the carbon atom
of the hydrazone function via a 5-exo ring-closure process.
When R3 ) CH3 and to a lesser extent when R1, R2
)
-(CH2)5-, the 5-exo mode of cyclization and the forma-
tion of linear compounds 25 become competitive. It is
well known that the presence of an alkyl substituent on
C-5 slows down the 5-exo ring closure of 5-hexenyl
radicals and thus allows the 6-endo process to become
predominant.16 However, in the case of 24e this 6-endo
carbocyclization implies the attack of the nucleophile
radical A on the sp2 nitrogen atom of the hydrazone
moiety, which is far less favorable than the attack on the
carbon.17 In the case of 24d , the 5-exo cyclization of the
corresponding cyclohexyl radical A is less favorable than
for species A formed from radical precursors 24a -c,
probably for steric reasons. The formation of products
25d ,e may be explained by the attack of the tin radical
on the less substituted trigonal carbon of the allenic
function. The very reactive vinyl radical18 B adds to the
carbon atom of the hydrazone in an unusual 4-exo-trig
addition.13,19 This cyclization is facilitated by the pres-
ence of the gem-dimethyl group on the R-carbon atom of
the hydrazone function, in agreement with recent similar
reports.19 The cyclobutyl aminyl radical C fragments
immediately into products 25d ,e with subsequent elimi-
nation of the tributyltin group.20
(C) Ch ir a l Allen e-Tet h er ed SAMP H yd r a zon e
(12). The interesting results obtained in the cyclization
of allene-tethered N,N-dimethylhydrazones 7-11
prompted us to prepare and cyclize the chiral hydrazone
12. In fact, asymmetric intramolecular carbocyclizations
mediated by chiral auxiliaries have not been extensively
studied,21 and our substrates are ideal to test the asym-
metric induction in these processes. Our first choice was
the commercially available SAMP hydrazine. The radical
precursor was obtained by standard methodology from
2,2,5-trimethylhexa-3,4-dienal. In our experimental con-
ditions, compound 12 gave exclusively the cyclopentyl-
hydrazine derivative 26 (eq 2) in 78% yield and as an
inseparable mixture of diastereoisomers. The diastereo-
meric excess estimated by 1H NMR spectrometry was
1
about 50%. The H NMR spectrum of the mixture of the
(15) It should be noted that the stereoselectivities given in ref 5b
are incorrect.
(16) Beckwith, A. L. J . Tetrahedron 1981, 37, 3073-3100.
(17) Tomaszewski, M. J .; Warkentin, J . Tetrahedron Lett. 1992, 33,
2123-2126.
(18) Stork, G.; Baine, N. H. J . Am. Chem. Soc. 1982, 104, 2321-
2323 and references cited therein.
two diastereomers obtained is so complex that we did not
succeeded in analyzing it completely; fortunately, the
vinylic proton signals were completely separated to allow
us a correct diastereomeric excess estimation. We have
(19) (a) Araki, Y.; Endo, T.; Arai, Y.; Tanji, M.; Ishido, Y. Tetrahedron
Lett. 1989, 30, 2829-2832. (b) Pattenden, G.; Reynolds, S. J . Tetra-
hedron Lett. 1991, 32, 259-262. (c) Fremont, S. L.; Belletire, J . L.;
Ho, D. M.; Kodama, K.; Sato, T.; Ikeda, M. Synlett 1993, 649-650. (d)
Ogura, K.; Sumitani, N.; Kayano, A.; Igushi, H.; Fugita, M. Chem. Lett.
1992, 1487-1488.
(20) (a) Maeda, Y.; Inglod, K. U. J . Am. Chem. Soc. 1980, 102, 328-
331. (b) Newcomb, M.; Park, S.-U. Kaplan, J .; Marquardt, D. J .
Tetrahedron Lett. 1985, 26, 5651-5654. (c) Bowman, W. R.; Clark,
D. N.; Marnon, R. J . Tetrahedron 1994, 50, 1275-1294.
(21) For a review, see: Porter, N. A.; Giese, B.; Curran, D. P. Acc.
Chem. Res. 1991, 24, 296-304.

Cyclization of Allene-Tethered Oxime Ethers
J . Org. Chem., Vol. 62, No. 5, 1997 1207
128.3, 128.4, 148.7. Anal. Calcd for C14H19NO: C, 77.38; H,
8.81; N, 6.44. Found: C, 77.10; H, 9.12; N, 6.31] and
1-[(ben zyloxy)a m in o]-2-eth ylen ecyclop en ta n e (19) (0.005
g, 11%) as an oil: Rf ) 0.31 (6% ethyl acetate/hexane); IR (film)
1
ν 2960, 2860, 1640, 1455, 1360, 990, 910, 740, 695 cm-1; H
NMR (CDCl3) δ 1.40-1.97 (6 H, m), 2.35 (1 H, quintet, J ) 8
Hz), 3.19 (1 H, q, J ) 8 Hz), 4.73 (2 H, s), 4.97 (1 H, br d, J )
10 Hz), 5.05 (1 H, br d, J ) 17 Hz), 5.62 (1 H, br s), 5.78 (1 H,
ddd, J ) 8, 10, 17 Hz), 7.40 (5 H, br s); 13C NMR (CDCl3) δ
22.9, 30.2, 31.4, 47.5, 67.2, 76.2, 112.3, 114.4, 128.2, 128.3,
128.5, 141.4. Anal. Calcd for C14H19NO: C, 77.38; H, 8.81;
N, 6.44. Found: C, 77.20; H, 9.02; N, 6.41.
been unable to determine the absolute configuration at
the new stereocenter in the major isomer.
1-[(Ben zyloxy)a m in o]-2-m eth ylen ecyclop en ta n e (21).
Triethylborane (1 M in hexanes, 0.30 mL, 0.30 mmol) was
added to a degassed solution of allenic oxime ether 2 (0.115 g,
0.57 mmol) and tributyltin hydride (0.20 mL, 1.48 mmol) in
dry toluene (30 mL) under Ar. The reaction mixture was
stirred at 70 °C for 1 h 30 min, triethylborane (1 M in hexanes,
0.30 mL, 0.30 mmol) and tributyltin hydride (0.20 mL, 1.48
mmol) were added, the reaction mixture was stirred at 70 °C
overnight, more triethylborane (1 M in hexanes, 0.30 mL, 0.30
mmol) and tributyltin hydride (0.20 mL, 1.48 mmol) were
added, and the reaction mixture was stirred at 70 °C for 1 h
and then concentrated under reduced pressure. The crude
product (1.15 g) was purified by flash column chromatography.
Elution with dichloromethane/hexane (20/80 and 40/60) gave
the cyclized products (20) (0.135 g, 48%) as an oil. The product
(20) (0.135 g, 0.27 mmol) was stirred in a solution of HCl/EtOH
(5 mL) at rt overnight and the solvent removed under reduced
pressure. The residue was partitioned between saturated
sodium bicarbonate solution (5 mL) and dichloromethane (10
mL) and extracted with dichloromethane (3 × 10 mL). The
combined organic extract was dried over sodium sulfate and
concentrated under reduced pressure. The crude product (0.12
g) was purified by flash column chromatography. Elution with
ethyl acetate/hexane (3/97) gave 1-[(ben zyloxy)a m in o]-2-
m eth ylen ecyclop en ta n e (21) (0.033 g, 59%) as an oil: Rf )
0.38 (5% ethyl acetate/hexane); IR (film) ν 2960, 2860, 1610,
1500, 1455, 1025, 915, 740, 700 cm-1; 1H NMR (CDCl3) δ 1.48-
1.86 (4 H, m), 2.26 (2 H, m), 3.78 (1 H, m), 4.66 (2 H, s), 4.98
(2 H, m), 5.33 (1 H, br s), 7.30 (5 H, m); 13C NMR (CDCl3) δ
23.1, 30.8, 32.0, 64.1, 76.5, 109.7, 127.8, 128.2, 128.4, 137.8,
151.4; MS (70 eV) m/z 203 (M, 0.13), 92 (7), 91 (100), 77 (7).
Anal. Calcd for C13H17NO: C, 76.81; H, 8.43; N, 6.89.
Found: C, 76.53; H, 8.72; N, 7.18. 1-[(Ben zyloxy)a m in o]-
2-m eth ylen ecyclop en ta n e (21) was obtained in 34% overall
from allenic oxime ether (6) using the crude cyclization mixture
for the destannylation.
In summary, in this work we have shown that the
tributyltin hydride-mediated cycloisomerization of allene-
tethered oxime ethers or hydrazones is a convenient
method for the preparation of (vinylstannyl)cyclopentyl-
amine derivatives. The site-directed intermolecular at-
tack of the tributyltin radical at the allene moiety and
the final size of the ring after cycloisomerization depends
on the type of substitution in the substrate. Some
general trends can be observed: (1) In crowded substrates
having full substitution at Câ or at the terminal-trigonal
carbon, the steric hindrance favors attack at the digonal
carbon. (2) When different positions in the allene are
free for attack, the kinetically more favored irreversible
mode of cyclizations (5-exo > 6-exo > 6-endo) determines
the ratio of isomers or the final size of the ring. Finally,
the acid-promoted destannylation of the resulting vinyltin
intermediates has afforded unsaturated cyclopentylamine
derivatives in good chemical yield.
Exp er im en ta l Section
Reactions were monitored by TLC using precoated silica gel
aluminum plates containing a fluorescent indicator (Merck,
5539). Detection was done by UV (254 nm) followed by
charring with sulfuric-acetic acid spray, 1% aqueous potas-
sium permanganate solution, or 0.5% phosphomolybdic acid
in 95% EtOH. Anhydrous Na2SO4 was used to dry organic
solutions during workup, and the removal of solvents was
carried out under vacuum with a rotary evaporator. Flash
column chromatography was performed using Kieselgel 60
(230-400 mesh, Merck) and hexane-ethyl acetate mixtures
as eluent. 1H and 13C NMR spectra were recorded with a
Varian VXR-300S spectrometer, using tetramethylsilane as
internal standard.
Gen er a l P r oced u r e for th e Cycliza tion of th e â-Allen ic
Oxim e Eth er s. Bu3SnH (1.2 equiv) and AIBN (0.2 equiv)
were added to a benzene solution (0.02 M) of the O-methyl
oxime 3-6. After this solution was degassed with a stream
of argon, the mixture was refluxed and monitored by TLC until
the starting material had disappeared. The reaction was
monitored by TLC. After evaporation of the solvent, the crude
product was purified by flash chromatography over silica gel.
1-(Tr i-n -b u t ylst a n n yl)-3,3,5,5-t e t r a m e t h yl-4-(m e t h -
oxya m in o)cyclop en ten e (22a ). Reaction of 3 (1 g, 5.98
mmol) with Bu3SnH (2.09 g, 7.18 mmol) and AIBN (0.196 g,
1.19 mmol) in benzene (300 mL) during 24 h produced 22a
(2.1 g, 77%) as a colorless oil after purification by column
chromatography (pentane/diethyl ether 96/4): IR (film) ν 2960,
1-[(Ben zyloxy)am in o]-2-m eth ylen ecycloh exan e (18) and
1-[(Ben zyloxy)a m in o]-2-eth ylen ecyclop en ta n e (19). Tri-
ethylborane (1 M in hexanes, 0.15 mL, 0.15 mmol) was added
to a degassed solution of allenic oxime ether 1 (0.065 g, 0.30
mmol) and tributyltin hydride (0.10 mL, 0.74 mmol) in dry
toluene (15 mL) under Ar. The reaction mixture was stirred
at 70 °C for 3 h, triethylborane (1 M in hexanes, 0.15 mL, 0.15
mmol) and tributyltin hydride (0.10 mL, 0.74 mmol) were
added, and the reaction mixture was stirred at 70 °C overnight
and concentrated under reduced pressure. The crude product
(0.53 g) was purified by flash column chromatography. Elution
with ethyl acetate/hexane (0/100 and 2/98) gave the cyclized
product 17 (0.110 g, 72%) as an oil. The mixture of product
17 (0.104 g, 0.20 mmol) was stirred in a solution of HCl/EtOH
(4 mL) at rt for 2 h 45 min and the solvent removed under
reduced pressure. The residue was partitioned between water
(10 mL) and hexane (10 mL) and extracted with hexane (3 ×
5 mL). The combined organic extract was concentrated under
reduced pressure. The crude product (0.10 g) was purified by
flash column chromatography. Elution with ethyl acetate/
hexane (0/100 and 2/98) gave 1-(ben zyloxy)a m in o]-2-m eth -
ylen ecycloh exa n e (18) (0.020 g, 45%) as an oil [Rf ) 0.43
(6% ethyl acetate/hexane); IR (film) ν 2920, 2860, 1460, 900,
1
2850, 1575, 1460 cm-1; H NMR (CDCl3) δ 0.87 (15 H, t, J )
7.3 Hz), 0.90 (3 H, s), 0.94 (3 H, s), 1.13 (3 H, s), 1.14 (3 H, s),
1.29 (6 H, sext, J ) 7 Hz), 1.45 (6 H, m), 3.01 (1 H, s), 3.49 (3
H, s), 5.42 (1H, s); 13C NMR (CDCl3) δ 9.9, 13.7, 23.0, 23.8,
27.4, 29.2, 30.2, 31.1, 48.6, 52.7, 60.7, 76.1, 149.2, 151.0.
1-(Tr i-n -b u t ylst a n n yl)-3,3,5-t r im e t h yl-4-(m e t h oxy-
a m in o)cyclop en ten e (22b). Reaction of 4 (1 g, 6.53 mmol)
with Bu3SnH (2.28 g, 7.84 mmol) and AIBN (0.214 g, 1.3 mmol)
in benzene (325 mL) during 26 h provided 22b (2.07 g, 74%)
after purification by column chromatography (pentane/diethyl
740, 700 cm-1; H NMR (CDCl3) δ 1.55 (4 H, m), 1.83 (2 H,
ether 92/8): IR (film) ν 3400, 2900, 2850, 1580, 1470 cm-1
.
1
m), 2.07 (1 H, m), 2.33 (1 H, m), 3.54 (1 H, dd, J ) 4, 7 Hz),
4.74 (2 H, s), 4.80 (2 H, s), 5.57 (1 H, s), 7.40 (5 H, m); 13C
NMR (CDCl3) δ 23.0, 28.1, 31.6, 33.7, 62.8, 76.6, 107.6, 127.7,
Anal. Calcd for C21H43NOSn: C, 56.77; H, 9.75; N, 3.15.
Found: C, 56.61; H, 9.9; N, 3.2. The 1H and 13C NMR were
recorded on a mixture of two isomers (cis 2/3-trans 1/3): 1H

1208 J . Org. Chem., Vol. 62, No. 5, 1997
Marco-Contelles et al.
NMR (CDCl3) (major isomer) δ 0.86 (18 H, t, J ) 7.5 Hz,
including 3 H, s), 0.93 (3 H, s), 1.13 (3 H, d, J ) 7 Hz); 1.28 (6
H, sext, J ) 7.5 Hz), 1.45 (6 H, m) 2.91 (1 H, quin d, J ) 8 Hz,
J ) 1 Hz), 3.35 (1 H, d, J ) 8 Hz), 3.52 (3 H, s), 5.53 (1 H, d,
J ) 1.2 Hz); 13C NMR (CDCl3) δ 9.5, 13.7, 16.0, 24.0, 27.3,
29.2, 29.6 47.5, 47.7, 61.0, 69.7, 145.5 150.8; 1H NMR (CDCl3)
(minor isomer) δ 0.86 (15 H, t, J ) 7.5 Hz), 0.88 (3 H, s), 0.95
(3 H, s), 1.13 (3 H, d, J ) 7 Hz), 1.28 (6 H, sext, J ) 7.5 Hz),
1.45 (6 H, m) 2.43 (1 H, quin d, J ) 8, 2.3 Hz), 2.89 (1 H, d, J
) 8 Hz), 3.50 (3 H, s), 5.49 (1 H, d, J ) 2.3 Hz); 13C NMR
(CDCl3) δ 9.6, 13.7, 20.8, 21.5, 27.3, 29.0, 29.2, 47.7, 48.9, 61.2,
77.3, 144.6, 151.4.
dd, J ) 5.9, 2.2 Hz); 13C NMR (CDCl3) δ 19.5, 21.5, 29.1, 43.0,
47.2, 61.2, 76.8, 131.6, 140.3.
5-E t h yl-3,3,5-t r im et h yl-4-(m et h oxya m in o)cyclop en -
ten e (23c). Treatment of 22c (0.9 g, 1.9 mmol) with a
saturated solution of HCl in ether (40 mL) produced 23c (0.29
g, 83%) in a cis/trans ratio of 80/20: IR (film) ν 2290, 1470
cm-1. Anal. Calcd for C11H21NO: C, 58.48; H, 10.03; N, 2.96.
Found: C, 58.44; H, 10.01; N, 2.96. NMR data: 1H NMR
(CDCl3) (major isomer) δ 0.84 (3 H, t, J ) 7.5 Hz), 0.90 (3 H,
s), 0.98 (3 H, s), 1.14 (3 H, s), 1.45 (2 H, q, J ) 7.5 Hz); 3.10 (1
H, s), 3.48 (3 H, s), 5.31 (1 H, d, J ) 6 Hz), 5.35 (1 H, d, J )
6 Hz); 13C NMR (CDCl3) δ 9.3, 21.3, 23.4 30.1, 34.4, 47.2, 50.7,
1
60.8, 72.49, 135.3, 138.5; H NMR (CDCl3) (minor isomer) δ
1-(Tr i-n -bu tylsta n n yl)-5-eth yl-3,3,5-tr im eth yl-4-(m eth -
oxya m in o)cyclop en ten e (22c). Reaction of 5 (1.2 g, 6.63
mmol) with Bu3SnH (1.93 g, 7.95 mmol) and AIBN (0.217 g,
1.32 mmol) in benzene (330 mL) during 49 h provided 22c (2.9
g, 91%) after purification by column chromatography (pentane/
0.77 (3 H, t, J ) 7.5 Hz), 0.90 (3 H, s), 0.95 (3 H, s), 0.95 (3 H,
s), 1.12 (3 H, s), 1.47 (2 H, q, J ) 7.5 Hz), 3.07 (1 H, s), 3.49 (3
H, s), 5.37 (1 H, d, J ) 6 Hz), 5.44 (1 H, d, J ) 6 Hz); 13C NMR
(CDCl3) δ 8.9, 23.4, 26.1, 29.1, 30.3, 47.0, 50.4, 60.8, 77.1, 135.5,
138.7.
diethyl ether 98/2): IR (film) 2900, 2800, 1575, 1455 cm-1
.
3,3-Dim et h yl-4-(m et h oxya m in o)cyclop en t en e (23d ).
Treatment of 22d (0.68 g, 1.58 mmol) with a saturated solution
of HCl in ether (30 mL) produced 23d (0.109 g, 53.5%): IR
Anal. Calcd for C23H47NOSn: C, 58.48; H, 10.03; N, 2.96.
Found: C, 58.44; H, 10.01; N, 2.96. The 1H and 13C NMR were
recorded on a mixture of two isomers (88% cis-12% trans);
1H NMR (CDCl3) (major isomer) δ 0.80-0.91 (24 H, compl m),
0.98 (3 H, s), 1.13 (3 H, s), 1.29 (6 H, sext, J ) 7.4 Hz), 1.44 (6
H, m), 3.17 (1 H, s), 3.47 (3 H, s), 5.43 (1 H, s); 13C NMR
(CDCl3) δ 9.9, 10.2, 13.6, 13.7, 22.9, 23.4, 27.4, 29.2, 34.5, 49.1,
56.2, 60.7, 70.7, 149.5, 150.30; 1H NMR (CDCl3) (minor isomer)
δ 0.80 to 0.91 (24 H, compl m), 0.96 (3 H, s), 1.12 (3 H, s), 1.32
(6 H, sext, J ) 7.2 Hz), 1.61 (6 H, m), 3.03 (1 H, s), 3.47 (3 H,
s), 5.45 (1 H, s); 13C NMR (CDCl3) δ 9.6, 9.96, 13.7, 17.5, 22.9,
23.4, 27.4, 29.2, 30.1, 49.1, 56.2, 60.7, 70.7, 149.5, 150.3.
1
(film) ν 3250, 3040, 2950, 1610, 1465 cm-1; H NMR (CDCl3)
δ 0.94 (3 H, s), 1.12 (3 H, s), 2.09 (1 H, ddt, J ) 16.4, 7.5, 2.1
Hz), 2.52 (1 H, dddd, J ) 16.4, 7.5, 2.5, 1.5 Hz), 3.39 (1 H, t,
J ) 7.5 Hz), 3.50 (3 H, s), 5.44 (1 H, dbr t, J ) 6, 1.8 Hz), 5.48
(1 H, dbr, t, J ) 6, 2.1 Hz); 13C NMR (CDCl3) δ 20.9, 28.4,
36.2, 46.3, 61.4, 68.6, 125.3, 141.7.
Gen er a l P r oced u r e for th e Cycliza tion of th e â-Allen ic
N,N-Dim eth ylh yd r a zon es. In a typical experiment, a ben-
zene solution of Bu3SnH (2 equiv) and AIBN (0.2 equiv) was
slowly added to a refluxing benzene solution (0.02 M) of
hydrazone 7-11. The mixture was refluxed until the starting
material disappeared (TLC analysis). After evaporation of the
solvent the crude product was purified by flash chromatogra-
phy.
1-(Tr i-n -bu tylstan n yl)-5,5-dim eth yl-4-(m eth oxyam in o)-
cyclop en ten e (22d ). Exposure of 6 (1 g, 7.19 mmol) to
Bu3SnH (2.51 g, 8.63 mmol) and AIBN (0.236 g, 1.44 mmol)
in benzene (350 mL) during 48 h provided 22d (1.13 g, 37%)
after purification by column chromatography (pentane/diethyl
ether 98/2): IR (liquid film) ν 3300, 2900, 2800, 1570, 1460
1-(Tr i-n -b u t ylst a n n yl)-3,3,5,5-t et r a m et h yl-4-(N,N-d i-
m eth ylh yd r a zin o)cyclop en ten e (24a ). Exposure of 7 (1.26
g, 7 mmol) to Bu3SnH (4.08 g, 14 mmol) and AIBN (0.23 g, 1.4
mmol) in benzene (170 mL) during 32 h produced 24a (2.9 g,
89%) as a colorless oil after purification by column chroma-
tography (pentane/diethyl ether 98/2): IR (film) ν 2954, 2805,
1
cm-1; H NMR (CDCl3) δ 0.86 (9 H, t, J ) 7.3 Hz), 0.87 (6 H,
t, J ) 8.3 Hz), 0.90 (3 H, s), 1.12 (3 H, s), 1.30 (6 H, sext, J )
7.3 Hz), 1.44 (6 H, m), 2.20 (1 H, ddd, J ) 16.2 Hz, J ) 7.6,
2.0 Hz), 2.57 (1 H, ddd, J ) 16.2, 7.6, 2.5 Hz), 3.36 (1 H, t, J
) 7.6 Hz), 3.51 (3 H, s), 5.63 (1H, dd, J ) 2.5, 2.0 Hz); 13C
NMR (CDCl3) δ 9.9, 13.7, 21.5, 27.4, 29.2, 38.2, 51.5, 61.3, 69.3,
136.5, 156.2.
1
2765, 1582, 1463, 1361 cm-1; H NMR (CDCl3) δ 0.94 (9 H, t,
J ) 7.3 Hz), 1.03 (6 H, t, J ) 8.2 Hz), 1.14 (3 H, s), 1.17 (3 H,
s), 1.23 (3 H, s), 1.30 (3 H, s), 1.39 (6 H, sext, J ) 7.3 Hz), 1.62
(6 H, m), 1.74 (1 H, br m), 2.26 (6 H, s), 2.90 (1 H, s), 5.65 (1
H, s); 13C NMR (CDCl3) δ 10.2, 13.9, 23.8, 24.7, 27.7, 29.6, 30.1,
31.1, 47.1, 49.6, 53.7, 73.7, 150.0, 151.3. Anal. Calcd for
C23H48N2Sn: C, 58.61; H, 10.26; N, 5.94. Found: C, 58.58; H,
10.32; N, 5.98.
Gen er a l P r oced u r e for th e Desta n n yla tion Rea ction
of Com p ou n d s 22a -d . The stannyl derivatives 22 were
treated with a saturated solution of HCl in diethyl ether at
room temperature. The reaction was monitored by TLC. After
evaporation of the solvent, the residue was taken up in ether
and washed twice with an aqueous solution of NaHCO3 and
once with water. The organic layer was dried (MgSO4) and
evaporated in vacuo. The crude cyclopentene 23a -d was
purified by column chromatography over silica gel followed by
bulb-to-bulb distillation.
1-(Tr i-n -b u t ylst a n n yl)-5-et h yl-3,3,5-t r im et h yl-4-(N,N-
d im eth ylh yd r a zin o)cyclop en ten e (24b). Exposure of 8
(1.35 g, 7 mmol) to Bu3SnH (4.08 g, 14 mmol) and AIBN (0.23
g, 1.4 mmol) in benzene (170 mL) during 24 h produced 24b
(2.61 g, 77%) as a colorless oil after purification by column
chromatography (pentane/diethyl ether 98/2): IR (film) ν 2905,
2800, 1430 cm-1. Anal. Calcd for C24H50N2Sn: C, 59.39; H,
10.38; N, 5.77. Found: C, 59.35; H, 10.40; N, 5.78. The 1H
and 13C NMR were recorded on a mixture of the both isomers
(cis 81%-trans 19%). Major isomer: 1H NMR (C6D6) δ 0.94
(12 H, t, J ) 7.3 Hz), 1.03 (6 H, m), 1.13 (3 H, s), 1.21 (3 H, s),
1.29 (3 H, s), 1.39 (6 H, sext, J ) 7.5 Hz), 1.48 (2 H, q, J ) 7.3
Hz), 1.62 (6 H, m), 1.76 (1 H, br m), 2.25 (6 H, s), 3.05 (1 H, s),
5.67 (1 H, s);
3,3,5,5-Tet r a m et h yl-4-(m et h oxya m in o)cyclop en t en e
(23a ). Treatment of 22a (0.75 g, 1.63 mmol) with a saturated
solution of HCl in ether (30 mL) produced 23a (0.228 g, 82%):
1
IR (film) ν 3040, 2980, 1470 cm-1; H NMR (CDCl3) δ 0.94 (6
H, s), 1.14 (6 H, s), 3.04 (1 H, s), 3.49 (3 H, s), 5.31 (2 H, s); 13
C
NMR (CDCl3) δ 23.1, 30.0, 47.2, 60.7, 75.5, 137.7. Anal. Calcd
for C10H19NO: C, 70.96; H, 11.31; N, 8.27. Found: C, 70.98;
H, 11.19; N, 8.18.
13C NMR (C6D6) δ 10.1, 10.2, 13.9, 23.9, 24.2,
3,3,5-Tr im eth yl-4-(m eth oxya m in o)cyclop en ten e (23b).
Treatment of 22b (1.36 g, 2.92 mmol) with a saturated solution
of HCl in ether (40 mL) produced 23b (0.348 g, 77%) in a cis/
trans ratio of 62/38: IR (film) ν 3250, 3025, 2850, 1615, 1470
cm-1. Anal. Calcd for C9H17NO: C, 69.63; H, 11.03; N, 9.02.
Found: C, 69.52; H, 11.13; N, 9.15. NMR data: 1H NMR
(CDCl3) (major isomer) δ 0.95 (3 H, s), 0.96 (1 H, d, J ) 8 Hz),
1.13 (3 H, s), 2.83 (1 H, quin dd, J ) 7.6, 2.6, 1.3 Hz), 3.37 (1
H, d, J ) 8 Hz), 3.51 (3 H, s), 5.43 (1 H, dd, J ) 5.9, 1.3 Hz),
5.55 (1 H, dd, J ) 5.9, 2.7 Hz); 13C NMR (CDCl3) δ 15.3, 24.0,
29.2, 41.7, 46.1, 60.9, 69.0, 132.5, 139.8; 1H NMR (CDCl3)
(minor isomer) δ 0.94 (3 H, s), 1.12 (3 H, d, J ) 7 Hz), 1.14 (3
H, s), 2.40 (1 H, quin br t, J ) 7.7, 2.0 Hz), 2.91 (1 H, d, J )
8 Hz), 3.50 (3 H, s), 5.33 (1 H, dd, J ) 5.9, 1.7 Hz), 5.39 (1 H,
27.8, 29.6, 30.1, 34.8, 47.2, 50.2, 57.1, 67.4, 149.6, 151.2. Minor
isomer: 1H NMR (C6D6) δ 0.94 (12 H, t, J ) 7.3 Hz), 1.03 (6
H, m), 1.07 (3 H, s), 1.15 (3 H, s), 1.24 (3 H, s), 1.39 (6 H, sext,
J ) 7.5 Hz), 1.48 (2 H, q, J ) 7.3 Hz), 1.62 (6 H, m), 1.76 (1 H,
br m), 2.24 (6 H, s), 2.95 (1 H, s), 5.68 (1 H, s); 13C NMR (C6D6)
δ 10.5, 11.4, 13.9, 23.4, 27.8, 29.6, 29.9, 30.4, 31.2, 47.1, 49.7,
57.3, 74.5, 149.7, 151.0.
1-(Tr i-n -bu tylsta n n yl)-3,3,5-tr im eth yl-4-(N,N-d im eth -
ylh yd r a zin o)cyclop en ten e (24c). Exposure of 9 (0.5 g, 3
mmol) to Bu3SnH (1.74 g, 6 mmol) and AIBN (0.1 g, 0.6 mmol)
in benzene (85 mL) during 24 h produced 24c (1.24 g, 77%) as
a colorless oil after purification by column chromatography
(pentane/diethyl ether 94/6). In this way, the cis (60%) and

Cyclization of Allene-Tethered Oxime Ethers
J . Org. Chem., Vol. 62, No. 5, 1997 1209
trans (40%) stereoisomers were separated. Cis isomer: IR
13.8, 21.1, 25.4, 26.5, 26.9, 27.4, 27.5, 29.2, 51.5, 51.6, 55.9,
69.4, 149.3, 150.0. Anal. Calcd for C24H50N2Sn: C, 59.39; H,
10.38; N, 5.77. Found: C, 59.35; H, 10.42; N, 5.80. 3-Iso-
(film) ν 2955, 2925, 2871, 2766, 1456, 1376, 1361 cm-1 1H
;
NMR (C6D6) δ 0.93 (9 H, t, J ) 7.3 Hz), 1.00 (6 H, t, J ) 8.0
Hz), 1.11 (3 H, s), 1.17 (3 H, s), 1.19 (3 H, d, J ) 7.2 Hz), 1.37
(6 H, sext, J ) 7.4 Hz), 1.60 (6 H, m), 1.77 (1 H, br m), 2.28 (6
H, s), 3.03 (1 H, dqd, J ) 7.7, 7.2, 1.1 Hz), 3.23 (1 H, d, J ) 7.7
Hz), 5.74 (1 H, d, J ) 1.1 Hz); 13C NMR (C6D6) δ 9.4, 13.6,
16.6, 24.5, 27.4, 28.9, 29.3, 47.3, 48.0, 49.6, 66.8, 146.0, 151.2.
Anal. Calcd for C22H46N2Sn: C, 57.78; H, 10.14; N, 6.12.
Found: C, 57.77; H, 10.23; N, 6.10. Trans isomer: IR (film) ν
p r op ylid en e-5-m et h ylh ex-4-en -2-on e
N,N-d im et h yl-
h yd r a zon e (25e). The 1H and 13C NMR of this compound
were recorded on a mixture of two stereoisomers, which are
the E (70%) and Z (30%) isomers of the hydrazone.
E
1
ster eoisom er : H NMR (CDCl3) δ 1.44 (3 H, d, J ) 1.1 Hz),
1.50 (3 H, br s), 1.59 (3 H, d, J ) 1.3 Hz), 1.61 (3 H, d, J ) 1.3
Hz), 1.78 (3 H, s), 2.34 (6 H, s), 5.50 (1 H, m); 13C NMR (CDCl3)
δ 17.2, 19.2, 20.8, 21.1, 25.7, 46.8, 122.2, 131.9, 132.8, 135.8,
167.6. Z ster eoisom er : 1H NMR (CDCl3) δ 1.45 (3 H, d, J )
1.1 Hz), 1.47 (3 H, br s), 1.48 (3 H, d, J ) 1.3 Hz), 1.61 (3 H,
d, J ) 1.3 Hz), 1.78 (3 H, s), 2.28 (6 H, s), 5.50 (1 H, m); 13C
NMR (CDCl3) δ 19.5, 20.3, 21.7, 23.4, 25.7, 47.0, 121.1, 128.0,
132.3, 135.0, 165.1.
2954, 2855, 2765, 1456, 1463, 1376 cm-1 1H NMR (C6D6) δ
;
0.93 (9 H, t, J ) 7.4 Hz), 0.98 (6 H, t, J ) 8.0 Hz), 1.15 (3 H,
s), 1.17 (3 H, d, J ) 7.0 Hz), 1.31 (3 H, s), 1.37 (6 H, sext, J )
7.4 Hz), 1.59 (6 H, m), 1.79 (1 H, br m), 2.27 (6 H, s), 2.61 (1
H, dqd, J ) 8.0, 7.0, 2.2 Hz), 2.78 (1 H, d, J ) 8.0 Hz), 5.74 (1
H, d, J ) 2.2 Hz); 13C NMR (C6D6) δ 9.8, 13.9, 20.6, 22.3, 27.6,
29.0, 29.6, 47.4, 49.9, 54.3, 74.3, 144.2, 152.7. Anal. Calcd
for C22H46N2Sn: C, 57.78; H, 10.14; N, 6.12. Found: C, 57.77;
H, 10.23; N, 6.10.
Cycliza tion of 2,2,5-Tr im eth ylh exa -3,4-d ien a l SAMP -
h yd r a zon e (12). Exposure of 12 (0.5 g, 2 mmol) to Bu3SnH
(0.7 g, 2.4 mmol) and AIBN (0.065 g, 0.4 mmol) in benzene
(100 mL) during 20 h produced the cyclized product 1-(tr i-n -
b u t ylst a n n yl)-3,3,5,5-t et r a m et h yl-4-(SAMP -h yd r a zin o)-
cyclop en ten e (26) (0.84 g, 78%) as a slightly yellow oil after
purification by column chromatography (pentane/diethyl ether
91/9): [R]255461A -74.4° (c 0.58, cyclohexane); IR (film) ν 2900-
Cycliza tion of 5-Cycloh exylid en e-2,2-d im eth ylp en ta -
3,4-d ien a l N,N-Dim eth ylh yd r a zon e (10). Exposure of 10
(0.88 g, 4 mmol) to Bu3SnH (4.66 g, 14 mmol) and AIBN (0.23
g, 1.4 mmol) in benzene (170 mL) during 58 h produced 24d
(1.18 g, 58%) as a colorless oil and 25d (0.22 g, 25%) as a white
solid (mp 35-40 °C), after purification by column chromatog-
raphy (gradient pentane/diethyl ether 96/4, 90/10, 85/15).
1 -( T r i - n -b u t y l s t a n n y l ) -3 , 3 -d i m e t h y l -4 -( N , N -
d im eth ylh yd r a zin o)sp ir o[4,5]d ecen e (24d ): IR (film) ν
1
2800, 1600, 1464, 1376, 1362 cm-1; H NMR (CDCl3) δ 0.82
(15 H, t, J ) 7 Hz), 0.84 (3 H, s), 0.87 (3 H, s), 0.90 (3 H, s),
0.92 (3 H, s), 1.03 (3 H, s), 1.06 (3 H, s), 1.07 (3 H, s), 1.23 (6
H, sext, J ) 7.2 Hz), 1.40 (6 H, m), 1.46 (2 H, m), 1.62 (2 H,
m), 1.83 (2 H, m), 2.76 (1 H, s), 3.26 (3 H, s), 3.24-3.32 (1 H,
m), 3.36-3.41 (1 H, m), 3.62 (1 H, br dd, J ) 8.9, 4.3 Hz), 5.36
(major) and 5.38 (minor) (1H, 2s); 13C NMR (CDCl3) (major
diastereomer) δ 9.8, 13.7, 20.8, 23.4, 24.1, 26.5, 27.3, 29.2, 29.6,
31.0, 48.3, 53.6, 56.9, 58.9, 66.2, 74.8, 75.8, 148.7, 151.7; (minor
diastereomer) δ 9.8, 13.7, 20.8, 23.3, 24.1, 26.5, 27.3, 29.2, 30.0,
31.6, 49.4, 52.5, 56.5, 58.9, 66.0, 74.5, 75.9, 150.1, 150.3. Anal.
Calcd for C27H54N2OSn: C, 59.89; H, 10.05; N, 5.17. Found:
C, 59.65; H, 10.00; N, 5.09.
1
2900, 2820, 1464, 1376 cm-1; H NMR (CDCl3) δ 0.82 (15 H,
2t, J ) 7.5 Hz), 0.96 (3 H, s), 1.06 (3 H, s), 1.24 (6 H, sext, J
) 7.5 Hz), 1.40 (6 H, m), 1.50 (9 H, m), 1.66 (1 H, m), 2.13 (1
H, br m), 2.54 (6 H, s), 2.77 (1 H, s), 5.37 (1 H, s); 13C NMR
(CDCl3) δ 10.4, 13.7, 23.6, 23.7, 24.1, 25.7, 27.4, 29.2, 30.6,
33.2, 40.9, 47.4, 50.6, 56.1, 74.7, 150.8, 150.8. Anal. Calcd
for C26H52N2Sn: C, 61.06; H, 10.24; N, 5.48. Found: C, 61.09;
H, 10.19; N, 5.46. 2-Cycloh exylid en e-4-m eth ylp en t-3-en a l
N,N-d im eth ylh yd r a zon e (25d ): IR (KBr) ν 2900, 2800, 1464,
1
1558, 1471, 1437 cm-1; H NMR (CDCl3) δ 1.49 (3 H, s), 1.58
Ackn owledgm en t. J. M.-C. thanks DGICYT (SAF94-
0818-C02-02), CICYT (CE93-0023), Comunidad Au-
to´noma de Madrid-Consejer´ıa de Educacio´n y Cultura
(AE-0094/94), and EU (Human Capital and Mobility;
Contract No. ERBCHRXCT 92-0027) for generous fi-
nancial support. J .M.-H. thanks Dr. R. Faure (Centre
Re´gional de RMN, Faculte´ de St. J e´roˆme, Marseille) for
recording and elucidating some of the NMR spectra. We
also thank Professor M. Bertrand for fruitful discus-
sions.
(6 H, m), 1.80 (3 H, s), 2.18 (2 H, m), 2.80 (6 H, s), 5.76 (1 H,
s), 7.43 (1 H, s); 13C NMR (CDCl3) δ 19.9, 25.3, 26.9, 27.7, 28.1,
30.0, 32.7, 43.1, 122.3, 127.0, 133.7, 135.5, 141.5; MS m/e (70
eV) 220 (M+, 34), 205 (42.7), 176 (92.4). Anal. Calcd for
C14H24N2: C, 76.31; H, 10.97; N, 12.71. Found: C, 76.78; H,
10.56; N, 12.37.
Cyclization of 3,3,6-Tr im eth ylh epta-4,5-dien -2-on e N,N-
Dim eth ylh yd r a zon e (11). Exposure of 11 (1.19 g, 6.13
mmol) to Bu3SnH (2.14 g, 7.36 mmol) and AIBN (0.20 g, 1.22
mmol) in benzene (300 mL) during 11 h produced 24e (0.47 g,
16.2%) and 25e (0.78 g, 57.2%) as colorless oils after purifica-
tion by column chromatography (gradient pentane/diethyl
ether 96/4, pentane/ethyl acetate 80/20). 1-(Tr i-n -bu tylsta n -
n yl)-3,3,4,5,5-p en t a m et h yl-4-(N,N-d im et h ylh yd r a zin o)-
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
1
cedures and H and 13C NMR spectra for compounds 1, 2, and
3-12 (3 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
cyclop en ten e (24e): IR (film) ν 2950, 2800, 1420, 1350 cm-1
;
1H NMR (CDCl3) δ 0.86 (6 H, t, J ) 8.2 Hz), 0.87 (9 H, t, J )
7.3 Hz), 0.96 (3 H, s), 0.97 (3 H, s), 1.01 (3 H, s), 1.05 (3 H, s),
1.06 (3 H, s), 1.30 (6 H, sext, J ) 7.3 Hz), 1.46 (6 H, m), 2.11
(1 H, br s), 2.42 (6 H, s), 5.37 (1 H, s); 13C NMR (CDCl3) δ 9.9,
J O962225R