Preparation of α-(2,2-diphenylhydrazino)lactones and related compounds by radical cyclization: Use of glyoxylic acid hydrazone derivatives

Article abstract of DOI:10.1021/jo0013655

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by β-bromo alcohols. The resulting esters undergo radical cyclization to α-(2,2-diphenylhydrazino)- or α-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a β-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 → 30) so that an α-amino lactone can be generated by acid hydrolysis of the cyclization product.

Full text of DOI:10.1021/jo0013655

J . Org. Chem. 2001, 66, 1233-1241
1233
P r ep a r a tion of r-(2,2-Dip h en ylh yd r a zin o)la cton es a n d Rela ted
Com p ou n d s by Ra d ica l Cycliza tion : Use of Glyoxylic Acid
Hyd r a zon e Der iva tives
Derrick L. J . Clive,* J unhu Zhang, Rajendra Subedi, Virginie Boue´tard,†
Sheldon Hiebert,† and Robert Ewanuk†
Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
derrick.clive@ualberta.ca
Received September 14, 2000
Glyoxylic acid diphenylhydrazone (2a ) and the corresponding O-benzyloxime (2b) are easily esterified
in high yield by â-bromo alcohols. The resulting esters undergo radical cyclization to R-(2,2-
diphenylhydrazino)- or R-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride.
Esters for radical cyclization were also made using a â-(phenylseleno) alcohol and an enol ether.
Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The
imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of
the nitrogen substituent (28 f 30) so that an R-amino lactone can be generated by acid hydrolysis
of the cyclization product.
A previous report from this laboratory1 described the
Sch em e 1
preparation of R-(2,2-diphenylhydrazino)- and R-[(phen-
ylmethoxy)amino]lactones 5a and 5b, respectively (Scheme
1), by acylation of alcohols (1 f 3a ,b), using reagents 2a
or 2b, followed by radical cyclization (3a ,b f 4a ,b f
5a ,b). In subsequent publications, the method was ap-
plied to alcohols of the carbohydrate series2 and was used
to synthesize the amino acid antibiotic furanomycin.3
Here we describe in detail the methodological aspects of
the reactions summarized in Scheme 1.
Our studies were undertaken with a view to using
radical cyclization methods as a route to R-amino acids.
In the event, although the equivalency between R-hy-
drazino lactones and amino acids was demonstrated,2,3
seen extensive use in ionic reactions10 and, recently (in
the form of its esters and amides), in radical processes.11
After the preliminary report,1 we made a number of
related reagents (2c12-2h ) by the same process of
condensation between glyoxylic acid and the appropriate
amine derivative. These compounds were prepared so
that we could examine the effect of reagent structure on
the efficiency of the radical cyclization and on the
opportunities for manipulating the hydrazino group in
the cyclization products.
the conversion, in the cases we examined,2,3 was not
straightforward.
The cyclization of radicals onto carbon-nitrogen double
bonds, especially as in O-alkyl oximes4,5 and diphenyl-
hydrazones,5-7 is a well-established process, and such
imine-like radical acceptors were easily incorporated into
reagents that were appropriate for our plans. Thus,
glyoxylic acid reacts readily with N,N-diphenylhydrazine
to afford crystalline 2a , which had actually been reported
before8 but had not been used in radical chemistry.
Reagent 2b was accessible just as easily, using O-benzyl
hydroxylamine, and was also a known compound;9 it has
* To whom correspondence should be addressed.
† Summer undergraduate researcher.
(1) Clive, D. L. J .; Zhang, J . Chem. Commun. 1997, 549-550.
(2) Zhang, J .; Clive, D. L. J . J Org. Chem. 1999, 64, 770-779.
(3) Zhang, J .; Clive, D. L. J . J . Org. Chem. 1999, 64, 1754-1757.
(4) (a) Bartlett, P. A.; McLaren, K. L.; Ting, P. C. J . Am. Chem. Soc.
1988, 110, 1633-1634. (b) Cf. Hart, D. J .; Seely, F. L. J . Am. Chem.
Soc. 1988, 110, 1631-1633.
(9) Herscheid, J . D. M.; Colstee, J . H.; Ottenheijm, H. C. J . J . Org.
Chem. 1981, 46, 3346-3348.
(10) For example, see the following: (a) Kolasa, T.; Sharma, S. K.;
Miller, M. J . Tetrahedron 1988, 44, 5431-5440. (b) Hanessian, S.;
Yang, R.-Y. Tetrahedron Lett. 1996, 37, 5273-5276. (c) ref 9.
(11) For example, see the following: (a) Miyabe, H.; Fujishima, Y.;
Naito, T. J . Org. Chem. 1999, 64, 2174-2175. (b) Miyabe, H.; Ushiro,
C.; Ueda, M.; Yamakawa, K.; Naito, T. J . Org. Chem. 2000, 65, 176-
185.
(5) Review: Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543-
17594.
(6) Sturino, C. F.; Fallis, A. G. J . Org. Chem. 1994, 59, 6514-6516.
(7) (a) Bowman, W. R.; Stephenson, P. T.; Terrett, N. K.; Young, A.
R. Tetrahedron Lett. 1994, 35, 6369-6372. (b) Bowman, W. R.;
Stephenson, P. T.; Terrett, N. K.; Young, A. R. Tetrahedron 1995, 51,
7959-7980.
(12) Severin, T.; Supp, W.; Manninger, G. Chem. Ber. 1979, 112,
3013-3022.
(8) Barber, H. J .; Lunt, E. J . Chem. Soc. 1965, 1468-1473.
10.1021/jo0013655 CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/25/2001

1234 J . Org. Chem., Vol. 66, No. 4, 2001
Clive et al.
Ta ble 1a
a
b
Isomer ratios given after compound numbers. The individual isomers were separated.
With 2a and 2b in handsand, later, the other reagents
2c-2h , as wellswe prepared the esters listed in Table
1. These were easily made by DCC-mediated coupling of
the reagents with â-bromo- or â-(phenylseleno) alcohols13
or, in the case of compound 24b, by adding NBS to a
mixture of 4,5-dihydrofuran and reagent 2a . The semi-
carbazone reagent 2d was too insoluble in common
solvents (MeCN, DMF, EtOAc, CH2Cl2, acetone, sul-
folane) for effective coupling with alcohols. For one of
the esters (9b) we obtained an X-ray crystal structure.
The data show that the CdN double bond has the E
geometry, and all the atoms lie close to a plane,
except for the bromine, which is perpendicular to that
plane.
The radical cyclizations were conducted by simulta-
neously adding toluene solutions16 of Bu3SnH and AIBN
by double syringe pump to a refluxing solution of the
substrate in the same solvent. At the end of the addition,
(14) For example, see the following: (a) Clive, D. L. J . J . Chem. Soc.,
Chem. Commun. 1974, 100. (b) Nicolaou, K. C.; Claremon, D. A.;
Barnette, W. E.; Seitz, S. P. J . Am. Chem. Soc. 1979, 101, 3704-3706.
(15) For example, see the following: Sharpless, K. B.; Lauer, R. F.
J . Am. Chem. Soc. 1973, 95, 2697-2699.
(16) We have used PhH in one case (see structure 16a and footnote
†† in ref 1) in order to demonstrate that the reaction works also at the
reflux temperature of this solvent. The solvent is incorrectly specified
as PhMe in ref 2.
(13) â-(Phenylseleno) alcohols are easily made from alkenes: (see
ref 14) or epoxides (see ref 15).

R-(2,2-Diphenylhydrazino)lactones
J . Org. Chem., Vol. 66, No. 4, 2001 1235
Sch em e 2
refluxing was continued for an arbitrary periodsgenerally
2-3 h. In a few cases (entries 8 and 17) Ph3SnH was used
but without significant influence on the results.
R-Phenylseleno derivatives may be used but, on the
basis of limited experience (Table 1, cf. entries 13 and
14), we find that bromides give better results in the
radical cyclization.
Reagent 2c coupled smoothly with alcohol 13a 17 (Table
1, entry 9) but, although dimethylhydrazones18 and
acylgermane dimethylhydrazones19 cyclize satisfactorily,
the radical cyclization step in the present case was not
clean and was clearly inefficient; the reagent was not
examined further. Bromides 8b and 9b gave even more
complex mixtures on attempted radical cyclization (en-
tries 3 and 4), and we conclude that glyoxylate-derived
CdNNHC(O)NMe2, CdNNHCO2Me, and CdNNMe2
groups are unsuitable as radical acceptors.20
Where the newly formed ring is produced on an
existing cyclic structure, the ring fusion geometry21 is cis
for [3.3.0] and [4.3.0] systems (Table 1, entries 12-16,
18, and 19) but both cis and trans ring fused products
are formed in the case of the [5.3.0] bicycle (entry 17).
The acyclic starting materials of entries 6, 7, 8, and 10
gave isomer mixtures, and for the cis ring fused products
(entries 12-19) both epimers at the position R to the
carbonyl were obtained with little, if any, selectivity. In
four cases (12c, 12c′, 12c′′, 12c′′′; 15c, exo-18c, en d o-
18c; exo-23c, en d o-23c) the individual isomers could be
separated, and tentative stereochemical assignments
were made (except for 15c) on the basis of NOE experi-
ments (see Experimental Section).
Bromide 23b gave two types of product: two isomers,
tentatively identified as 23c′, resulting from the typical
cyclization, and another pair of isomers (exo-23c, en d o-
23c) that are formed by 1,2-acyloxy migration22 of the
initial radical. The rearrangement affords a benzylic
radical and is evidently faster than cyclization, since exo/
en d o-23c is the major product.
R-hydrazono lactone (10d ), rather than the product of
simple de-arylation, was isolated.
As a potential method of generating R-amino lactones
by a route that does not involve hydrogenolysis (cf. 6c f
6d ), we also examined the imino ester 28 (Scheme 2),
which is so constituted that the initial radical cyclization
product (see 29) could lead directly to an imine (29 f
30) which would be expected to undergo easy hydrolysis.
The required ester (28) was prepared in several straight-
forward steps, summarized in Scheme 2 (17a f 25 f 26
f 28). In the event, bromide 28 behaved as expected and
underwent radical cyclization to imines 30, which were
hydrolyzed to the desired R-amino lactone 31, whose
stereochemistry at C(3) was tentatively assigned as
shown. Although 31 was obtained as a single isomer
(after recrystallization), we assume, by analogy with our
other results, that the precursor (30) was a mixture of
C(3) epimers. We did not attempt to generalize the
cyclization/hydrolysis process, however, as we were un-
able to prepare a reagent (comparable to 2a ) from 27 and
glyoxylic acid; such a reagent would have given access
to esters of type 28 in a single step by coupling with
bromo alcohols.
We have examined briefly various modifications to the
R-hydrazino lactones23 produced by the radical cycliza-
tion. Hydrogenation in an acidic medium served to
convert 6c into the corresponding R-amino lactone, which
was trapped and isolated as the hydrochloride salt 6d
(eq 1). We also treated 10c with DDQ (eq 2); however,
Con clu sion
Of the glyoxylic acid derivatives we have examined,
the N,N-diphenylhydrazone appears to be the best, in
terms of performance and ease of preparation, and the
methodology summarized in Scheme 1 represents an easy
route to R-hydrazino lactones. As illustrated in other
work from this laboratory,2,3 such compounds can be
transformed into unusual amino acid derivatives. The
O-benzyl oxime derivatives also cyclized satisfactorily.
With one of the N,N-diphenylhydrazones we encountered
a competing acyloxy radical rearrangement, which was
facilitated by formation of a benzylic radical. We have
also demonstrated an example of an unusual radical
displacement (Scheme 2).24
desaturation occurred more rapidly than oxidative re-
moval of the p-methoxybenzene groups so that the
(17) Yoon, U. C.; Kim, D. U.; Lee, C. W.; Choi, Y. S.; Lee, Y.-J .;
Ammon, H. L.; Mariano, P. S. J . Am. Chem. Soc. 1995, 117, 2698-
2710.
(18) Tauh, P.; Fallis, A. G. J . Org. Chem. 1999, 64, 6960-6968.
(19) Iserloh, U.; Curran, D. P. J . Org. Chem. 1998, 63, 4711-4716.
(20) Simple aldehyde hydrazones containing the CdNNHCOPh or
CdNNHCONH2 subunits do cyclize (see ref 7).
(21) Clive, D. L. J .; Cheshire, D. R.; Set, L. J . Chem. Soc., Chem.
Commun. 1987, 353-355.
(23) R-Hydrazino- and R-(hydroxy)amino γ-lactones are not well-
known. For some examples, see the following: (a) Kamenecka, T. M.;
Danishefsky, S. J . Angew. Chem., Int. Ed. Engl. 1998, 37, 2995-2998.
(b) Black, G. G.; Sainsbury, M. J . Chem. Res., Synop. 1986, 332-333.
(c) Pedersen, B. Acta Chem. Scand., Ser. B 1980, 34, 429-433. (d)
Paulsen, H.; Kuhne, H. Carbohydr. Res. 1970, 13, 289-292. (e) Ross-
Petersen, K. J .; Hjeds, H. Dan. Tidsskr. Farm. 1969, 43, 188-193;
Chem. Abstr. 1979, 72, 43314j.
(22) Beckwith, A. L. J .; Crich, D.; Duggan, P. J .; Yao, Q. Chem. Rev.
1997, 97, 3273-3312.

1236 J . Org. Chem., Vol. 66, No. 4, 2001
Clive et al.
hexane, gave 7b (2.371 g, 83%) as a pale yellow oil: FTIR (CH2-
Cl2 cast) 1727, 1598, 1497 cm-1; 1H NMR (CDCl3, 400 MHz) δ
3.57 (t, J ) 6.3 Hz, 2 H), 4.56 (t, J ) 6.3 Hz, 2 H), 5.32 (s, 2
H), 7.32-7.40 (m, 5 H), 7.58 (s, 1 H); 13C NMR (CD2Cl2, 50.3
MHz) δ 28.8 (t′), 64.9 (t′), 78.2 (t′), 128.4 (d′), 128.7 (d′), 128.8
(d′), 136.6 (s′), 141.1 (d′), 161.5 (s′); exact mass m/z calcd for
Exp er im en ta l Section
Gen er a l P r oced u r es. Unless stated to the contrary, the
general experimental procedures used previously25 were fol-
lowed. The symbols s′, d′, t′, and q′ used for 13C NMR signals
indicate zero, one, two, and three attached hydrogens, respec-
tively. The 13C signals for CHdN of the cyclization substrates
were often not visible in APT spectra, but were observed in
the broad band proton decoupled spectra.
(Dip h en ylh yd r a zon o)a cetic Acid (2a ). This procedure
differs from that reported8 in the literature. Glyoxylic acid
monohydrate (5.52 g, 60.0 mmol) was added to a stirred
solution of commercial Ph2NNH2‚HCl (13.2 g, 60.0 mmol) in
water (720 mL). Stirring was continued for 2 h, and the
precipitate was filtered off, washed with water, and dried
under oil-pump vacuum to afford 2a (13.9 g, 96%) as a gray
powder: mp 201-203 °C (lit.8 200-202 °C); 1H NMR (CD2-
Cl2, 300 MHz) δ 6.45 (s, 1 H), 7.15-7.25 (m, 4 H), 7.25-7.40
(m, 2 H), 7.40-7.55 (m, 4 H), 8.60-10.3 (br, 1 H).
[Di(4-Meth oxyp h en yl)h yd r a zon o]a cetic Acid (2f). Gly-
oxylic acid (0.8308 g, 9.025 mmol) was added to a stirred
solution of 16 (2.2034 g, 9.025 mmol) in MeOH (15.0 mL), and
stirring was continued overnight. Evaporation of the solvent
and flash chromatography of the residue over silica gel (4 cm
× 32 cm), using 60% EtOAc-hexane, gave 2f (2.3901 g, 88%)
as a crystalline solid.
Ben zoylp h en ylh yd r a zon oa cetic Acid (2g). Glyoxylic
acid monohydrate (1.45 g, 20.0 mmol) was added to a magneti-
cally stirred solution of N1-benzoylphenylhydrazine hydrochlo-
ride26 (5.0 g, 20.0 mmol) in water (300 mL). An extremely
sticky residue was formed within 10 min of the addition, so
the magnetic stirrer was replaced by a mechanical stirrer.
After 12 h, the mixture was filtered to obtain 2g (4.2759 g,
79%) as a crystalline solid.
C
11H1281BrNO3 286.9980, found 286.9976.
2-Br om oeth yl [Di(4-Meth oxyp h en yl)h yd r a zon o]a ce-
ta te (10b). The general procedure for coupling alcohols with
2a was followed, using 2f (2.321 g, 7.73 mmol), alcohol 6a
(1.0384 g, 8.50 mmol), DCC (1.7538 g, 8.50 mol), and DMAP
(0.0944 g, 0.773 mmol) in CH2Cl2 (15 mL). Flash chromatog-
raphy of the crude product over silica gel (4 cm × 32 cm), using
10% EtOAc-hexane, gave 10b (2.7981 g, 89%) as a crystalline
solid.
(R*,R*)-2-Br om o-1-pr opylpen tyl (Diph en ylh ydr azon o)-
a ceta te (11b). The general procedure for coupling alcohols
with 2a was followed, using 2a (1.60 g, 6.67 mmol), alcohol
11a 27 (930 mg, 4.45 mmol), DCC (1.38 g, 6.67 mmol), and
DMAP (81 mg, 0.67 mmol) in CH2Cl2 (25 mL). Flash chroma-
tography of the residue over silica gel (3 cm × 22 cm), using
5% EtOAc-hexane, gave 11b (1.88 g, 98%) as a pale yellow
oil.
(R*,R*)-2-Br om o-1-p r op ylp en t yl [(P h en ylm et h oxy)-
im in o]a ceta te (12b). The general procedure for coupling
alcohols with 2b was followed, using 2a (0.895 g, 5.00 mmol),
alcohol 11a 27 (1.15 g, 5.50 mmol), DCC (1.14 g, 5.50 mmol),
and DMAP (61.0 mg, 0.50 mmol) in CH2Cl2 (25 mL). Flash
chromatography of the residue over silica gel (3 cm × 30 cm),
using 10% EtOAc-hexane, gave 12b (1.85 g, 100%) as a
colorless oil: FTIR (CH2Cl2 cast) 1744, 1722, 1597, 1497 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 0.90-0.98 (m, 6 H), 1.30-1.50
(m, 3 H), 1.57-1.87 (m, 5 H), 4.05-4.11 (m, 1 H), 5.15-5.20
(m, 1 H), 5.33 (s, 2 H), 7.30-7.44 (m, 5 H), 7.60 (s, 1 H); 13C
NMR (CDCl3, 50.3 MHz) δ 13.3 (q′), 13.7 (q′), 18.6 (t′), 20.9
(t′), 34.0 (t′), 36.8 (t′), 56.5 (d′), 76.3 (d′), 78.2 (t′), 128.5 (d′),
128.7 (d′), 135.9 (s′), 140.7 (d′), 161.3 (s′); exact mass m/z calcd
for C17H2481BrNO3 371.0919, found 371.0917.
Gen er a l P r oced u r e for Cou p lin g of Alcoh ols w ith
Rea gen ts 2a or 2b. Glyoxylic acid diphenylhydrazone (2a )
or glyoxylic acid O-benzyloxime (2b) (1.2 equiv) was added to
a stirred mixture of the alcohol (1.0 equiv), DCC (1.32 equiv),
and DMAP (0.12 equiv) in dry CH2Cl2. Stirring was continued
for 12 h, and the mixture was then filtered. The insoluble
material was washed with dry CH2Cl2 and the combined
filtrates were evaporated to give a residue which was processed
as described for the individual experiments.
2-Br om o-1-p h en yleth yl (Dip h en ylh yd r a zon o)a ceta te
(13b). The general procedure for coupling alcohols with 2a was
followed, using 2a (265.5 mg, 1.106 mmol), alcohol 13a 17 (244.7
g, 1.217 mmol), DCC (251.1 mg, 1.217 mmol), and DMAP (13.6
mg, 0.111 mmol) in CH2Cl2 (5.5 mL). Flash Chromatography
of the residue over silica gel (1.7 cm × 35 cm), using first 20%
EtOAc-hexane, and then 30% EtOAc-hexane, gave 13b
(357.1 mg, 76%) as a yellow oil.
2-Br om o-2-p h en yleth yl (Dip h en ylh yd r a zon o)a ceta te
(15b). The general procedure for coupling alcohols with 2a was
followed, using 2a (281.4 mg, 1.172 mmol), alcohol 15a 28 (259.2
mg, 1.290 mmol), DCC (266.1 mg, 1.290 mmol), and DMAP
(14.3 mg, 0.117 mmol) in CH2Cl2 (5.9 mL). Flash Chromatog-
raphy of the residue over silica gel (1.7 cm × 35 cm), using
20% EtOAc-hexane, and rechromatography, using 10%
EtOAc-hexane, gave 15b (387.0 mg, 78%) as a colorless solid.
A portion was recrystallized from MeOH (32% recovery): mp
105-107 °C.
2-Br om oeth yl (Dip h en ylh yd r a zon o)a ceta te (6b). The
general procedure for coupling alcohols with 2a was followed,
using 2a (1.21 g, 5.00 mmol), alcohol 6a (0.685 g, 5.50 mmol),
DCC (1.14 g, 5.50 mmol), and DMAP (61.0 mg, 0.50 mmol) in
CH2Cl2 (25 mL). Flash chromatography of the residue over
silica gel (3 cm × 30 cm), using 10% EtOAc-hexane, gave 6b
(1.39 g, 80%) as a crystalline solid: mp 102-104 °C; FTIR
(CH2Cl2 cast) 1730, 1705, 1590, 1552 cm-1; H NMR (CDCl3,
1
300 MHz) δ 3.57 (t, J ) 6.3 Hz, 2 H), 4.52 (t, J ) 6.3 Hz, 2 H),
6.50 (s, 1 H), 7.15-7.50 (m, 10 H); 13C NMR (CDCl3, 50.3 MHz)
δ 28.5 (t′), 63.8 (t′), 123.0 (d′), 126.2 (d′), 129.9 (d′), 141.9 (s′),
164.0 (s′); exact mass m/z calcd for C16H1579BrN2O2 346.0317,
found 346.0326.
2-Br om oeth yl [(P h en ylm eth oxy)im in o]a ceta te (7b).
The general procedure for coupling alcohols with 2b was
followed, using 2b (1.790 g, 10.00 mmol), alcohol 6a (1.370 g,
11.00 mmol), DCC (2.270 g, 11.00 mmol), and DMAP (122 mg,
1.00 mmol) in CH2Cl2 (50 mL). Flash chromatography of the
residue over silica gel (4 cm × 30 cm), using 10% EtOAc-
3-Br om opr opyl (Diph en ylh ydr azon o)acetate (16b). The
general procedure for coupling alcohols with 2a was followed,
using 2a (1.21 g, 5.00 mmol), alcohol 16a (497 µL, 5.50 mmol),
DCC (1.14 g, 5.50 mmol), and DMAP (61 mg, 0.50 mmol) in
CH2Cl2 (25 mL). Flash chromatography of the residue over
silica gel (3 cm × 30 cm), using 10% EtOAc-hexane, gave 16b
(1.30 g, 72%) as a pale yellow oil: FTIR (CH2Cl2 cast) 1729,
(24) Radical displacement of a benzyl group from nitrogen: (a)
Bachi, M. D.; Denenmark, D. J . Am. Chem. Soc. 1989, 111, 1886-
1888. Displacement of an allylic radical from carbon: (b) Rajamannar,
T.; Balasubramanian, K. K. Tetrahedron Lett. 1994, 35, 637-640. (c)
Mehta, G.; Murthy, A. N.; Reddy, D. S.; Reddy, A. V. J . Am. Chem.
Soc. 1986, 108, 3443-3452. (d) Rawal, V. H.; Dufour, C.; Iwasa, S.
Tetrahedron Lett. 1995, 36, 19-22. Strain-assisted carbon-carbon
bond cleavage: (e) Sarkar, S.; Ghosh, S. Tetrahedron Lett. 1993, 34,
2987-2988. Radical displacement of a benzyl group from carbon of an
iminyl radical: (f) Poutsma, M. L.; Ibarbia, P. A. J . Org. Chem. 1969,
34, 2848-2855.
1703, 1589, 1552, 1493 cm-1 1H NMR (CDCl3, 400 MHz) δ
;
2.26 (quintet, J ) 6.3 Hz, 2 H), 3.52 (t, J ) 6.6 Hz, 2 H), 4.36
(t, J ) 6.0 Hz, 2 H), 6.47 (s, 1 H), 7.16-7.50 (m, 10 H); 13C
NMR (CDCl3, 50.3 MHz) δ 29.4 (t′), 31.5 (t′), 62.0 (t′), 122.1
(d′), 123.4 (d′), 125.9 (d′), 129.8 (d′), 141.8 (s′), 164.1 (s′); exact
mass m/z calcd for C17H1779BrN2O2 360.0473, found 360.0475.
tr a n s-2-Br om ocycloh exyl (Dip h en ylh yd r a zon o)a ce-
ta te (17b). The general procedure for coupling alcohols with
(25) Clive, D. L. J .; Wickens, P. L.; Sgarbi, P. W. M. J . Org. Chem.
1996, 61, 7426-7437.
(26) Yamamoto, H. J . Org. Chem. 1967, 32, 3693-3695.
(27) Van Ende, D.; Krief, A. Tetrahedron Lett. 1975, 2709-2712.
(28) Cowell, A.; Stille, J . K. J . Am. Chem. Soc. 1980, 102, 4193-
4198.

R-(2,2-Diphenylhydrazino)lactones
J . Org. Chem., Vol. 66, No. 4, 2001 1237
2a was followed, using 2a (1.21 g, 5.00 mmol), alcohol 17a 29
(0.895 g, 5.00 mmol), DCC (1.14 g, 5.50 mmol), and DMAP
(61 mg, 0.50 mmol) in CH2Cl2 (25 mL). Flash chromatography
of the residue over silica gel (1.6 cm × 30 cm), using 5%
EtOAc-hexane, gave 17b (1.80 g, 90%) as a pale yellow oil:
H), 5.3 (dt, J ) 7.8, 3.2 Hz, 1 H), 6.53 (s, 1 H), 7.18-7.52 (m,
10 H); 13C NMR (CD2Cl2, 75.5 MHz) δ 22.6 (t′), 24.9 (t′), 27.9
(t′), 31.3 (t′), 35.2 (t′), 57.2 (d′), 80.3 (d′), 122.7 (d′), 124.3 (d′),
126.5 (d′), 130.3 (d′), 142.5 (s′), 163.5 (s′); exact mass m/z calcd
for C21H2381BrN2O2 416.09225, found 416.09179.
FTIR (CH2Cl2 cast) 1728, 1702, 1590, 1552, 1494 cm-1
;
1H
tr a n s-2-Br om o-2,3-d ih yd r o-1H-in d en -1-yl (Dip h en yl-
h yd r a zon o)a ceta te (23b). The general procedure for coupling
alcohols with 2a was followed, using 2a (1.21 g, 5.00 mmol),
alcohol 23a (1.17 g, 5.50 mmol), DCC (1.14 g, 5.50 mmol), and
DMAP (61 mg, 0.50 mmol) in CH2Cl2 (25 mL). After evapora-
tion of the solvent, MeOH (10 mL) was added to the residue.
The resulting precipitate was filtered off and washed with
MeOH to give 23b (1.80 g, 82%) as a crystalline solid: mp
159-161 °C; FTIR (CH2Cl2 cast) 1728, 1701, 1589, 1549, 1487,
NMR (CDCl3, 300 MHz) δ 1.22-1.54 (m, 3 H), 1.67-2.00 (m,
3 H), 2.12-2.27 (m, 1 H), 2.30-2.42 (m, 1 H), 4.01-4.10 (m, 1
H), 5.00-5.10 (m, 1 H), 6.50 (s, 1 H), 7.14-7.50 (m, 10 H); 13
C
NMR (CD2Cl2, 50.3 MHz) δ 23.7 (t′), 25.9 (t′), 31.6 (t′), 36.1
(t′), 53.6 (d′), 76.3 (d′), 122.7 (d′), 124.3 (d′), 126.5 (d′), 130.4
(d′), 142.6 (s′), 163.7 (s′); exact mass m/z calcd for C20H2179BrN2O2
400.0786, found 400.0786.
tr a n s-2-Br om ocycloh exyl [(P h en ylm et h oxy)im in o]-
a ceta te (18b). The general procedure for coupling alcohols
with 2b was followed, using 2b (0.895 g, 5.00 mmol), alcohol
17a 29 (0.970 g, 5.42 mmol), DCC (1.14 g, 5.50 mmol), and
DMAP (61 mg, 0.50 mmol) in CH2Cl2 (25 mL). Flash chroma-
tography of the residue over silica gel (1.6 cm × 30 cm), using
3% EtOAc-hexane, gave 18b (1.50 g, 88%) as a colorless oil:
1
1458 cm-1; H NMR (CD2Cl2, 360 MHz) δ 3.29 (dd, J ) 17.1,
3.9 Hz, 1 H), 3.75 (dd, J ) 17.1, 6.5 Hz, 1 H), 4.58-4.62 (m, 1
H), 6.43 (d, J ) 3.2 Hz, 1 H), 6.48 (s, 1 H), 7.12-7.50 (m, 14
H); 13C NMR (CD2Cl2, 50.3 MHz) δ 41.9 (t′), 50.8 (d′), 84.2 (d′),
122.8 (d′), 123.7 (d′), 125.3 (d′), 126.4 (d′), 126.6 (d′), 127.9 (d′),
130.1 (d′), 130.4 (d′), 138.8 (s′), 142.0 (s′), 164.0 (s′); exact mass
m/z calcd for C23H1981BrN2O2 436.0609, found 436.0609.
tr a n s-3-Br om otetr a h yd r ofu r a n -2-yl (Dip h en ylh yd r a -
zon o)a ceta te (24b). NBS (1.48 g, 8.3 mmol) was added to a
cooled (-15 °C, ice-salt) and stirred solution of dihydrofuran
(24a ) (0.5287 g, 7.54 mmol) and 2a (1.99 g, 8.3 mmol) in THF
(10 mL). The mixture was stirred for 2 h and then stored at
-5 °C overnight. Evaporation of the solvent and flash chro-
matography of the residue over silica gel (1.7 cm × 34 cm),
using 15% EtOAc-hexane, gave 24b (2.12 g, 72%) as a foam:
FTIR (CH2Cl2 cast) 1744, 1724, 1598, 1452 cm-1 1H NMR
;
(CDCl3, 400 MHz) δ 1.25-1.52 (m, 3 H), 1.70-1.95 (m, 3 H),
2.12-2.23 (m, 1 H), 2.33-2.41 (m, 1 H), 4.02-4.09 (m, 1 H),
5.03-5.10 (m, 1 H), 5.33 (s, 2 H), 7.33-7.45 (m, 5 H), 7.57 (s,
1 H); 13C NMR (CDCl3, 100.6 MHz) δ 23.3 (t′), 25.5 (t′), 31.1
(t′), 35.6 (t′), 52.2 (d′), 77.1 (d′), 78.2 (t′), 128.5 (d′), 128.6 (d′),
128.7 (d′), 136.0 (s′), 141.0 (d′), 160.9 (s′); exact mass m/z calcd
for C15H1881BrNO3 341.0450, found 341.0453.
tr a n s-2-(P h en ylselen o)cycloh exyl (Dip h en ylh yd r a -
zon o)-a ceta te (19b). The general procedure for coupling
alcohols with 2a was followed, using 2a (1.77 g, 7.37 mmol),
alcohol 19a 30 (2.06 g, 8.11 mmol), DCC (1.68 g, 8.11 mmol),
and DMAP (89 mg, 0.74 mmol) in CH2Cl2 (40 mL). Flash
chromatography of the residue over silica gel (4 cm × 30 cm),
using 5% EtOAc-hexane, gave 19b (2.99 g, 85%) as a pale
yellow, viscous oil.
tr a n s-2-Br om ocyclopen tyl [Ben zoylph en ylh ydr azon o]-
a ceta te (20b). The general procedure for coupling alcohols
with 2a was followed, using 2g (0.192 g, 0.72 mmol), alcohol
20a 31 (0.13 g, 0.78 mmol), DCC (0.162 g, 0.79 mmol), and
DMAP (0.010 g, 0.08 mmol) in CH2Cl2 (30.0 mL). Flash
chromatography of the crude product over silica gel (1.7 cm ×
30 cm), using 2.5% MeOH-CH2Cl2, gave 20b (0.1653 g, 56%)
as an oil.
FTIR (CH2Cl2 cast) 1708, 1590, 1548, 1487, 1458 cm-1 1H
;
NMR (CD2Cl2, 400 MHz) δ 2.23-2.41 (m, 1 H), 2.61-2.81 (m,
1 H), 4.19-4.4 (m, 2 H), 4.42 (d, J ) 5.4 Hz, 1 H), 6.43-6.57
(m, 2 H), 7.03-7.61 (m, 10 H); 13C NMR (CD2Cl2, 100.6 MHz)
(several expected signals were not observed) δ 33.0 (t′), 44.9
(d′), 68.1 (t′), 96.2 (d′), 123.6 (d′), 130.5 (d′), 163.6 (s′); exact
mass m/z calcd for C18H1779BrN2O3 388.0422, found 388.0422.
The trans stereochemistry is assigned on the basis of mecha-
nistic considerations and the value of the coupling constant
for the OCHO proton (J ) 5.4 Hz).
Gen er a l P r oced u r e for Ra d ica l Cycliza tion . The sub-
strate was placed in a round bottom flask equipped with a
Teflon-coated stirring bar and a reflux condenser sealed with
a rubber septum. The system was flushed with Ar for 5-10
min, and dry PhMe was injected into the flask. The flask was
placed in an oil bath preheated to 110 °C, and individual
solutions of Bu3SnH and AIBN in PhMe were injected simul-
taneously by syringe pump over 10 h. Refluxing was continued
for an arbitrary period of 1-4 h after the addition. The reaction
mixture was cooled, and the solvent was evaporated to give a
residue which was processed as described for the individual
experiments.
3-(2,2-Diph en ylh ydr azin o)dih ydr o-2(3H)-fu r an on e (6c).
The general procedure for radical cyclization was followed,
using 6b (0.400 g, 1.15 mmol) in PhMe (70 mL), Bu3SnH (500
µL, 1.86 mmol) in PhMe (10 mL), and AIBN (20 mg, 0.12
mmol) in PhMe (10 mL). Flash chromatography of the residue
over silica gel (1.6 cm × 30 cm), using first 5% EtOAc-hexane
(500 mL) and then 10% EtOAc-hexane, gave 6c (234 mg, 75%)
as a crystalline solid: mp 92-93 °C; FTIR (CH2Cl2 cast) 1774
cm-1; 1H NMR (CD2Cl2, 300 MHz) δ 2.30-2.53 (m, 2 H), 3.84-
3.92 (m, 1 H), 4.14-4.24 (m, 1 H), 4.46 (td, J ) 8.7, 3.2 Hz, 1
H), 4.70 (s, 1 H), 7.03-7.40 (m, 10 H), 13C NMR (CD2Cl2, 75.5
MHz) δ 29.9 (t′), 55.8 (d′), 66.7 (t′), 120.7 (d′), 123.2 (d′), 129.6
(d′), 147.4 (s′), 175.9 (s′); exact mass m/z calcd for C16H16N2O2
268.1212, found 268.1210.
tr a n s-2-Br om ocyclop en tyl (Dip h en ylh yd r a zon o)a ce-
ta te (21b). The general procedure for coupling alcohols with
2a was followed, using 2a (667.0 mg, 2.76 mmol), alcohol 20a 31
(500.0 mg, 3.0 mmol), DCC (800.0 mg, 3.0 mmol), and DMAP
(37.0 mg, 0.30 mmol) in CH2Cl2 (10 mL). Flash chromatogra-
phy of the crude product over silica gel (1.7 cm × 30 cm), using
10% EtOAc-hexane, gave 21b (914.0 mg, 86%) as an oil: FTIR
(CHCl3 cast) 1727, 1701, 1667, 1651, 1551 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 1.50-2.53 (m, 6 H), 4.2-4.4 (m, 1 H), 5.3-
5.6 (m, 1 H), 6.45 (s, 1 H), 6.91-7.72 (m, 10 H); 13C NMR
(CDCl3, 75.5 MHz) (several expected signals were not observed)
δ 21.8 (t′), 29.6 (t′), 34.7 (t′), 53.1 (d′), 82.4 (d′), 123.6 (d′), 130.0
(t′), 163.8 (s′); exact mass m/z calcd for
C
19H1981BrN2O2
388.0609, found 388.0609.
tr a n s-2-Br om ocycloh ep tyl (Dip h en ylh yd r a zon o)a ce-
ta te (22b). The general procedure for coupling alcohols with
2a was followed, using 2a (168 mg, 0.070 mmol), alcohol 22a 32
(150 mg, 0.77 mmol), DCC (158 mg, 0.77 mmol), and DMAP
(8.5 mg, 0.07 mmol) in CH2Cl2 (5 mL). Flash chromatography
of the crude product over silica gel (1.7 cm × 35 cm), using
10% EtOAc-hexane, gave 22b (243.0 mg, 83%) as a light
yellow oil: FTIR (CH2Cl2 cast) 1726, 1700, 1590, 1493, 1457
cm-1; 1H NMR (CD2Cl2, 300 MHz) δ 1.52-1.90 (m, 7 H), 1.92-
2.21 (m, 2 H), 2.22-2.40 (m, 1 H), 4.31 (dt, J ) 7.9, 3.7 Hz, 1
Dih yd r o-3-[(p h en ylm et h oxy)a m in o]-2(3H )-fu r a n on e
(7c). The general procedure for radical cyclization was fol-
lowed, using 7b (0.315 g, 1.10 mmol) in PhMe (70 mL), Bu3-
SnH (474 µL, 1.76 mmol) in PhMe (10 mL), and AIBN (30 mg,
0.18 mmol) in PhMe (10 mL). Flash chromatography of the
residue over silica gel (1.6 cm × 30 cm), using first 10%
EtOAc-hexane (700 mL) and then 30% EtOAc-hexane, gave
7c (118 mg, 51%) as a colorless oil: FTIR (CH2Cl2 cast) 1774
(29) Gus, C. O.; Rosenthal, R. J . Am. Chem. Soc. 1955, 77, 2549.
(30) Toshimitsu, A.; Aoai, T.; Owada, H.; Uemura, S.; Okano, M.
Tetrahedron 1985, 41, 5301-5306.
(31) Overman, L. E.; Shim, J . J . Org. Chem. 1993, 58, 4662-4672.
(32) Gupta, A. K.; Kazlauskas, R. Tetrahedron: Asymmetry 1993,
4, 879-888.
1
cm-1; H NMR (CDCl3, 360 MHz) δ 2.22-2.42 (m, 2 H), 3.79
(td, J ) 8.9, 1.8 Hz, 1 H), 4.18-4.26 (m, 1 H), 4.38 (td, J )

1238 J . Org. Chem., Vol. 66, No. 4, 2001
Clive et al.
8.9, 3.8 Hz, 1 H), 4.71 (d, J ) 11.8 Hz, 1 H), 4.76 (d, J ) 11.8
Hz, 1 H), 6.12 (s, 1 H), 7.24-7.40 (m, 5 H); 13C NMR (CDCl3,
50.3 MHz) δ 26.4 (t′), 59.1 (d′), 66.2 (t′), 77.1 (t′), 128.1 (d′),
128.5 (d′), 128.6 (d′), 137.2 (s′), 175.6 (s′); exact mass m/z calcd
for C11H13NO3 207.0895, found 207.0896.
3-[2,2-Di(4-m eth oxyp h en yl)h yd r a zin o]d ih yd r o-2(3H)-
fu r a n on e (10c). The general procedure for radical cyclization
was followed using 10b (230 mg, 0.57 mmol) in PhMe (35 mL),
Bu3SnH (247.4 mg, 0.85 mmol) in PhMe (5 mL), and AIBN
(9.30 mg, 0.057 mmol) in PhMe (5 mL). Flash chromatography
of the crude product over silica gel (1.7 cm × 30 cm), using
20% EtOAc-hexane, gave 10c (133.1 mg, 71%) as a crystalline
solid.
3-(2,2-Dip h en ylh yd r a zin o)d ih yd r o-4,5-d ip r op yl-2(3H)-
fu r a n on e (11c). The general procedure for radical cyclization
was followed, using 11b (0.494 g, 1.15 mmol) in PhMe (70 mL),
Bu3SnH (474 µL, 1.76 mmol) in PhMe (10 mL), and AIBN (30
mg, 0.18 mmol) in PhMe (10 mL). Flash chromatography of
the residue over silica gel (1.6 cm × 28 cm), using 2% EtOAc-
hexane, gave a crude fraction which contained a small amount
of tributyltin residues (1H NMR, 400 MHz). Further purifica-
tion by flash chromatography over silica gel (1.6 cm × 28 cm),
using 3% EtOAc-hexane, gave 11c (330 mg, 82%) as a pale
yellow oil, which was a 2:3:2:3 mixture (1H NMR) of four
chromatographically inseparable isomers.
(3r,4r,5r)-Dih yd r o-3-[(p h e n ylm e t h oxy)a m in o]-4,5-
d ip r op yl-2(3H )-fu r a n on e (12c), (3r,4r,5â)-Dih yd r o-3-
[(p h en ylm et h oxy)a m in o]-4,5-d ip r op yl-2(3H )-fu r a n on e
(12c′), (3r,4â,5â)-Dih yd r o-3-[(p h en ylm eth oxy)a m in o]-4,5-
d ip r op yl-2(3H)-fu r a n on e (12c′′), a n d (3r,4â,5r)-Dih yd r o-
3-[(p h e n ylm e t h oxy)a m in o]-4,5-d ip r op yl-2(3H )-fu r a n -
on e (12c′′′).
11.6 Hz, 1 H), 4.75 (d, J ) 11.6 Hz, 1 H), 6.02 (d, J ) 2.7 Hz,
1 H), 7.28-7.40 (m, 5 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 14.0
(q′), 14.4 (q′), 19.5 (t′), 21.3 (t′), 29.0 (t′), 37.0 (t′), 44.1 (d′),
62.2 (d′), 76.3 (t′), 85.4 (d′), 128.4 (d′), 128.8 (d′), 137.6 (s′), 175.8
(s′); exact mass m/z calcd for C17H25NO3 291.1834, found
291.1827. Irradiation of the Ha 1H NMR signal for 12c′ caused
an NOE of 5% in the signal for the Hb and 0% for the Hc signal.
Compound 12c′′ had the following characteristics: FTIR
(CH2Cl2 cast) 1778 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 0.88-
1.00 (m, 6 H), 1.25-1.65 (m, 8 H), 2.60-2.70 (m, 1 H), 3.36 (d,
J ) 10.5 Hz, 1 H), 4.49-4.56 (m, 1 H), 4.69 (d, J ) 0.9 Hz, 2
H), 6.13 (s, 1 H), 7.28-7.40 (m, 5 H); 13C NMR (CD2Cl2, 100.6
MHz) δ 14.0 (q′), 14.3 (q′), 19.5 (t′), 21.0 (t′), 30.3 (t′), 32.7 (t′),
40.6 (d′), 64.6 (d′), 77.4 (t′), 80.9 (d′), 128.3 (d′), 128.7 (d′), 129.1
(d′), 137.9 (s′), 175.4 (s′); exact mass m/z calcd for C17H25NO3
291.1834, found 291.1836. Irradiation of the Ha 1H NMR signal
for 12c′′ caused an NOE of 13% in the signal for the Hb and
0% for the Hc signal.
Compound 12c′′′ had the following characteristics: FTIR
(CH2Cl2 cast) 1776 cm-1; 1H NMR (CDCl3, 400 MHz) δ 0.91-
0.98 (m, 6 H), 1.30-1.72 (m, 8 H), 2.20-2.30 (m, 1 H), 3.41 (d,
J ) 9.9 Hz, 1 H), 4.02 (td, J ) 8.5, 3.5 Hz, 1 H), 4.72 (d, J )
2.8 Hz, 2 H), 6.15 (s, 1 H), 7.27-7.38 (m, 5 H); 13C NMR
(CDCl3, 50.3 MHz) δ 13.9 (q′), 14.3 (q′), 18.9 (t′), 20.4 (t′), 34.2
(t′), 37.0 (t′), 42.7 (d′), 66.5 (d′), 76.9 (t′), 83.0 (d′), 128.0 (d′),
128.4 (d′), 128.7 (d′), 137.3 (s′), 175.1 (s′); exact mass m/z calcd
for C17H25NO3 291.1834, found 291.1831. Irradiation of the Ha
1H NMR signal for 12c′′′ caused an NOE of 4% in the signal
for the Hb and 5% for the Hc signal.
3-(2,2-Diph en ylh ydr azin o)dih ydr o-5-ph en yl-2(3H)-fu r a-
n on e (13c). The general procedure for radical cyclization was
followed, using 13b (364.2 mg, 0.861 mmol) in PhMe (54 mL),
Bu3SnH (0.35 mL, 1.29 mmol) in PhMe (7.5 mL), and AIBN
(14.9 mg, 0.0911 mmol) in PhMe (7.5 mL). Flash chromatog-
raphy of the residue several times over silica gel (1.7 cm × 35
cm), using 10% EtOAc-hexane, gave crude (1H NMR) 13c
(192.1 mg, ca. 64%) as a yellow oil. Some of the material (86.5
mg, 0.251 mmol) crystallized from 5% EtOAc-hexane, and a
portion was recrystallized from MeOH to give 13c (9.4 mg,
35% recovery) as a mixture [ca. 1:1 (1H NMR)] of two isomers.
3-(2,2-Diph en ylh ydr azin o)dih ydr o-4-ph en yl-2(3H)-fu r a-
n on e (15c). The general procedure for radical cyclization was
followed, with the indicated modifications, using 15b (250.3
mg, 0.592 mmol) in PhMe (37 mL), Bu3SnH (0.24 mL, 0.89
mmol) in PhMe (5.25 mL), and AIBN (10.3 mg, 0.063 mmol)
in PhMe (5.25 mL). The residue was dissolved in Et2O (50 mL),
and the solution was agitated for 40 min in a sonicator
[Branson, model B-12, 80 W] with an aqueous solution of KF
(515.9 mg, 8.88 mmol) in water (10 mL).33 The precipitate of
Bu3SnF was filtered off and the ethereal phase of the filtrate
was separated. The aqueous layer was washed with Et2O and
the combined organic extracts were dried (Na2SO4) and
evaporated. Flash chromatography of the residue over silica
gel (1.7 cm × 35 cm), using 10% EtOAc-hexane, gave the two
individual isomers of 15c (117.5 mg, 55.5 mg, 85% in all) as
yellow oils, each of which was characterized spectroscopically,
but we did not assign the stereochemistry to the individual
isomers, as the observed J CHN-CHPh values were comparable.
3-(2,2-Dip h e n ylh yd r a zin o)t e t r a h yd r o-2H -p yr a n -2-
on e (16c) a n d P r op yl (Dip h en ylh yd r a zon o)a ceta te (16c′).
The general procedure for radical cyclization was followed,
using 16b (0.415 g, 1.15 mmol) in PhMe (70 mL), Bu3SnH (474
µL, 1.76 mmol) in PhMe (10 mL), and AIBN (30 mg, 0.18
mmol) in PhMe (10 mL). Flash chromatography of the residue
over silica gel (1.6 cm × 30 cm), using 5% EtOAc-hexane, gave
16c′ (66 mg, 20%) as a crystalline solid and 16c (163 mg, 50%)
as a colorless oil.
The general procedure for radical cyclization was followed,
using 12b (0.407 g, 1.10 mmol) in PhMe (70 mL), Bu3SnH (474
µL, 1.76 mmol) in PhMe (10 mL), and AIBN (30 mg, 0.18
mmol) in PhMe (10 mL). Flash chromatography of the residue
over silica gel (1.6 cm × 30 cm), using 5% EtOAc-hexane, gave
a crude fraction which contained a small amount of tributyltin
residues (1H NMR, 400 MHz). Further purification by flash
chromatography over silica gel (1.6 cm × 24 cm), using 5%
EtOAc-hexane, gave a 1:3:1:2 mixture (250 mg, 78% in all)
1
of 12c, 12c′, 12c′′, and 12c′′′ (as judged by H NMR measure-
ments). Flash chromatography of the mixture over silica gel
(1.6 cm × 25 cm), using 3% EtOAc-hexane, gave four
fractions, #1-#4. Each fraction was further purified by flash
chromatography over silica gel (1 cm × 20 cm), using 2%
EtOAc-hexane. Fractions #1, #2, #3, and #4 gave 12c, 12c′,
12c′′, and 12c′′′, respectively, as colorless oils.
Compound 12c had the following characteristics: FTIR
(CH2Cl2 cast) 1773 cm-1; 1H NMR (CDCl3, 400 MHz) δ 0.89-
0.98 (m, 6 H), 1.29-1.61 (m, 7 H), 1.72-1.81 (m, 1 H), 2.52-
2.60 (m, 1 H), 3.98 (dd, J ) 7.6, 3.2 Hz, 1 H), 4.36-4.42 (m, 1
H), 4.72 (s, 2 H), 5.90 (s, 1 H), 7.27-7.37 (m, 5 H); 13C NMR
(CDCl3, 50.3 MHz) δ 13.9 (q′), 14.5 (q′), 19.4 (t′), 20.9 (t′), 25.7
(t′), 32.4 (t′), 41.9 (d′), 63.7 (d′), 82.3 (d′), 128.1 (d′), 128.5 (d′),
128.6 (d′), 137.2 (s′), 174.6 (s′); exact mass m/z calcd for C17H25
-
Compound 16c′ had the following characteristics: mp 83-
NO3 291.1834, found 291.1833. Irradiation of the Ha 1H NMR
signal for 12c caused an NOE of 7.2% in the signal for Hb and
3.5% for the Hc signal.
84 °C; FTIR (CH2Cl2 cast) 1728, 1702, 1590, 1556, 1494 cm-1
;
1H NMR (CDCl3, 200 MHz) δ 1.00 (t, J ) 7.4 Hz, 3 H), 1.73
(sextet, J ) 7.1 Hz, 2 H), 4.20 (t, J ) 6.8 Hz, 2 H), 6.52 (s, 1
H), 7.12-7.50 (m, 10 H); 13C NMR (CDCl3, 50.3 MHz) δ 10.4
Compound 12c′ had the following characteristics: FTIR
(CH2Cl2 cast) 1773 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 0.92-
0.99 (m, 6 H), 1.25-1.73 (m, 8 H), 2.11-2.20 (m, 1 H), 3.75
(dd, J ) 8.5, 2.9 Hz, 1 H), 4.21-4.28 (m, 1 H), 4.70 (d, J )
(33) Leibner, J . E.; J acobus, J . J . Org. Chem. 1979, 44, 449-450.

R-(2,2-Diphenylhydrazino)lactones
J . Org. Chem., Vol. 66, No. 4, 2001 1239
(q′), 22.1 (t′), 66.3 (t′), 122.4 (d′), 124.3 (d′), 126.0 (d′), 130.0
(d′), 143.0 (s′), 164.8 (s′); exact mass m/z calcd for C17H18N2O2
282.1368, found 282.1374.
Compound 16c had the following characteristics: FTIR
(CH2Cl2 cast) 1732 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.80-
2.01 (m, 3 H), 2.22-2.37 (m, 1 H), 3.64-3.73 (m, 1 H), 4.27-
4.37 (m, 2 H), 5.06 (s, 1 H), 7.00-7.31 (m, 10 H); 13C NMR
(CD2Cl2, 50.3 MHz) δ 21.6 (t′), 25.3 (t′), 55.7 (d′), 69.8 (t′), 120.6
(d′), 122.9 (d′), 129.5 (d′), 147.6 (s′), 171.7 (s′); exact mass m/z
calcd for C17H18N2O2 282.1368, found 282.1366.
in PhMe (10 mL). Flash chromatography of the residue over
silica gel (1.6 cm × 28 cm), using 3% EtOAc-hexane, gave
19c (≡17c) (70 mg, 20%) as a pale yellow oil, which was a 1:1
mixture (1H NMR) of isomers. The spectroscopic data were
identical to those of 17c obtained previously.
(3r,3a â,7a â)- a n d (3r,3a r,7a r)-3-(2-Ben zoyl-2-p h en yl-
h ydr azin o)h exah ydr o-2H-cyclopen ta[b]fu r an -2-on e (20c).
The general procedure for radical cyclization was followed,
using 20b (74.7 mg, 0.18 mmol) in PhMe (11.2 mL), Bu3SnH
(78.7 mg, 0.27 mmol) in PhMe (1.55 mL), and AIBN (3.1 mg,
0.02 mmol) in PhMe (1.6 mL). The solvent was evaporated and
the residue was diluted with Et2O (5 mL) and saturated
aqueous KF (5 mL). The resulting mixture was stirred for 3.5
h and filtered through Celite using Et2O. The aqueous layer
was extracted with Et2O, and the combined organic layers were
dried (Na2SO4) and evaporated. Flash chromatography of the
residue over silica gel (1.7 cm × 30 cm), using 25% EtOAc-
hexane, gave 20c (29.5 mg, 49%) as an oil, which was a
mixture [ca. 1:1 (1H NMR)] of two isomers.
(3r,3a â,7a â)- a n d (3r,3a r,7a r)-3-(2,2-Dip h en ylh yd r a -
zin o)h exa h yd r o-2(3H)-ben zofu r a n on e (17c). The general
procedure for radical cyclization was followed, using 17b (0.450
g, 1.12 mmol) in PhMe (70 mL), Bu3SnH (474 µL, 1.76 mmol)
in PhMe (10 mL), and AIBN (50 mg, 0.31 mmol) in PhMe (10
mL). Flash chromatography of the residue over silica gel (1.6
cm × 30 cm), using 3% EtOAc-hexane, gave 17c (0.261 g,
72%) as a pale yellow oil which was a 1:1 mixture (1H NMR)
1
of isomers: FTIR (CH2Cl2 cast) 1773 cm-1; H NMR (CD2Cl2,
400 MHz) δ 1.10-1.90 (m, 8 H), 2.15-2.25 (m, 0.49 H), 2.48-
2.68 (m, 0.69 H), 3.65 (dd, J ) 6.2, 1.3 Hz, 0.41 H), 4.00 (dd,
J ) 6.2, 1.3 Hz, 0.42 H), 4.37-4.41 (m, 0.49 H), 4.48 (s, 0.91
H), 4.78 (dd, J ) 12.2, 5.6 Hz, 0.34 H), 7.00-7.35 (m, 10 H);
13C NMR (CD2Cl2, 100.6 MHz) δ 20.1 (t′), 21.4 (t′), 22.1 (t′),
23.1 (t′), 23.4 (t′), 25.3 (t′), 27.7 (t′), 29.0 (t′), 39.8 (d′), 41.1
(d′), 60.7 (d′), 63.3 (d′), 76.8 (d′), 78.2 (d′), 120.8 (d′), 121.1 (d′),
123.2 (d′), 123.4 (d′), 129.6 (d′), 129.7 (d′), 147.6 (s′), 147.9 (s′),
175.6 (s′), 176.2 (s′); exact mass m/z calcd for C20H22N2O2
322.1681, found 322.1678.
(3r,3a â,7a â)- a n d (3r,3a r,7a r)-3-(2,2-Dip h en ylh yd r a -
zin o)h exa h yd r o-2H-cyclop en ta [b]fu r a n -2-on e (21c). The
general procedure for radical cyclization was followed, using
21b (100.0 mg, 0.26 mmol) in PhMe (16.0 mL), Bu3SnH (113.0
mg, 0.39 mmol) in PhMe (2.2 mL), and AIBN (4.5 mg, 0.02
mmol) in PhMe (2.3 mL). The solvent was evaporated and the
residue was diluted with Et2O (5 mL) and saturated aqueous
KF (5 mL). The resulting mixture was stirred for 4 h and
filtered through Celite using Et2O. The aqueous layer was
extracted with Et2O, and the combined organic layers were
dried (Na2SO4) and evaporated to give 21c (49.6 mg, 63%) as
an oil, which was a mixture [ca. 1:1.4 (1H NMR)] of two
isomers: FTIR (CHCl3 cast) 1767 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.30-2.11 (m, 6 H), 2.73-3.04 (m, 1 H), 3.42-3.53
(m, 1 H), 4.01 (d, J ) 9.0 Hz, 1 H), 4.71-4.90 (m, 0.6 H), 5.03-
5.24 (m, 0.5 H), 6.82-7.59 (m, 10 H); 13C NMR (CDCl3, 75.5
MHz) δ 23.7 (t′), 23.9 (t′), 25.2 (t′), 31.3 (t′), 33.1 (t′), 33.2 (t′),
44.1 (d′), 44.5 (d′), 59.5 (d′), 63.7 (d′), 85.0 (d′), 86.1 (d′), 120.6
(d′), 120.7 (d′), 123.1 (d′), 129.3 (d′), 129.4 (d′), 147.1 (s′), 147.3
(s′), 175.3 (s′), 176.1 (s′); exact mass m/z calcd for C19H20N2O2
308.1524, found 308.1521.
(3r,3a r,7a r)-H exa h yd r o-3-[(p h en ylm et h oxy)a m in o]-
2(3H)-ben zofu r a n on e (exo-18c) a n d (3r,3a â,7a â)-Hexa -
h y d r o -3-[(p h e n y lm e t h o x y )a m in o ]-2(3H )-b e n zo fu r a -
n on e (en d o-18c).
3-(2,2-Dip h en ylh yd r a zin o)octa h yd r o-2H-cycloh ep ta [b]-
fu r a n -2-on e (22c). The general procedure for radical cycliza-
tion was followed, using 22b (590 mg, 1.42 mmol) in PhMe
(90 mL), Bu3SnH (0.57 mL, 2.13 mmol) in PhMe (12 mL), and
AIBN (22.9 mg, 0.14 mmol) in PhMe (12 mL). Flash chroma-
tography of the crude product over silica gel (1.7 cm × 35 cm),
using 15% EtOAc-hexane, gave 22c (268.9 mg, 56%) as a
mixture of four isomers, of which only one could be separated
from the others. Two fractions were obtained from the chro-
matography; one (235.2 mg) consisted of three isomers and
the other (33.7 mg) was a single isomer. The mixed fraction
had the following characteristics: FTIR (CH2Cl2 cast) 1769
The general procedure for radical cyclization was followed,
using 18b (0.202 g, 0.595 mmol) in PhMe (40 mL), Bu3SnH
(240 µL, 0.893 mmol) in PhMe (5 mL), and AIBN (20 mg, 0.12
mmol) in PhMe (5 mL). Flash chromatography of the residue
over silica gel (1.6 cm × 28 cm), using first 3% EtOAc-hexane
(500 mL) and then 10% EtOAc-hexane, gave exo-18c (51 mg,
33%) as a crystalline solid and en d o-18c (50 mg, 32%) as a
colorless oil.
exo-18c had the following characteristics: FTIR (CH2Cl2
cast) 1775 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 1.22-1.75 (m,
7 H), 1.95-2.03 (m, 1 H), 2.59-2.67 (m, 1 H), 3.56 (dd, J )
9.4, 2.6 Hz, 1 H), 4.50-4.58 (m, 1 H), 4.68 (s, 2 H), 6.11 (d, J
) 2.3 Hz, 1 H), 7.25-7.39 (m, 5 H); 13C NMR (CD2Cl2, 50.3
MHz) δ 21.2 (t′), 22.0 (t′), 24.7 (t′), 29.7 (t′), 37.2 (d′), 62.9 (d′),
77.36 (d′), 77.44 (t′), 128.2 (d′), 128.6 (d′), 129.0 (d′), 137.8 (s′),
175.4 (s′); exact mass m/z calcd for C15H19NO3 261.1365, found
261.1361.
en d o-18c had the following characteristics: mp 71.5-72.5
°C; FTIR (CH2Cl2 cast) 1774 cm-1; 1H NMR (CD2Cl2, 400 MHz)
δ 0.93-0.40 (m, 3 H), 1.52-1.73 (m, 4 H), 2.13-2.26 (m, 1 H),
2.50-2.57 (m, 1 H), 4.11 (dd, J ) 6.1, 4.0 Hz, 1 H), 4.41-4.45
(m, 1 H), 4.70 (s, 2 H), 5.91 (d, J ) 3.5 Hz, 1 H), 7.30-7.40 (m,
5 H); 13C NMR (CD2Cl2, 50.3 MHz) δ 20.1 (t′), 22.7 (t′), 23.3
(t′), 27.7 (t′), 39.3 (d′), 66.6 (d′), 76.80 (t′), 76.81 (d′), 128.3 (d′),
128.7 (d′), 128.8 (d′), 138.1 (s′), 174.8 (s′); exact mass m/z calcd
for C15H19NO3 261.1365, found 261.1359. Irradiation of the Ha
1H NMR signal for exo-18c caused an NOE of 8% in the signal
for Hb and 1% for the Hc signal; in the case of en d o-18c, the
corresponding values were 12% and 11%, respectively.
(3r,3a â,7a â)- a n d (3r,3a r,7a r)-3-(2,2-Dip h en ylh yd r a -
zin o)h exa h yd r o-2(3H)-ben zofu r a n on e [19c (≡ 17c)]. The
general procedure for radical cyclization was followed, using
19b (500 mg, 1.05 mmol) in PhMe (70 mL), Bu3SnH (370 µL,
1.37 mmol) in PhMe (10 mL), and AIBN (69 mg, 0.42 mmol)
cm-1 1H NMR (CD2Cl2, 300 MHz) δ 1.12-1.65 (m, 4.71 H),
;
1.65-2.16 (m, 4.74 H), 2.16-2.68 (m, 1 H), 2.86-3.0 (m, 0.19
H), 3.61-3.70 (m, 0.47 H), 4.03 (d, J ) 7.8 Hz, 0.45 H), 4.12
(dt, J ) 10.2, 4.3 Hz, 0.08 H), 4.5-4.64 (m, 0.89 H), 4.66-4.8
(m, 0.62 H), 4.92 (s, 0.14 H), 7.01-7.39 (m, 10 H); 13C NMR
(CD2Cl2, 75.5 MHz) δ 21.9 (t′), 22.2 (t′), 25.2 (t′), 25.6 (t′), 25.8
(t′), 27.1 (t′), 27.7 (t′), 28.8 (t′), 29.2 (t′), 30.3 (t′), 31.0 (t′), 31.2
(t′), 31.4 (t′), 31.5 (t′), 33.7 (t′), 45.7 (d′), 46.1 (d′), 50.8 (d′),
60.7 (d′), 62.1 (d′), 63.0 (d′), 81.4 (d′), 82.7 (d′), 83.8 (d′), 120.6
(d′), 120.7 (d′), 121.2 (d′), 123.0 (d′), 123.1 (d′), 123.5 (d′), 129.5
(d′), 129.6 (d′), 129.7 (d′), 147.4 (s′), 147.6 (s′), 148.0 (s′), 175.3
(s′), 175.4 (s′); exact mass calcd for C21H24N2O2 336.1837, found
336.1832.
The single isomer had the following characteristics: FTIR
(CH2Cl2 cast) 1777 cm-1; 1H NMR (CD2Cl2, 300 MHz) δ 1.48-
1.95 (m, 9 H), 2.19-2.32 (m, 1 H); 2.34-2.47 (m, 1 H); 3.68
(dd, J ) 6.3, 1.6 Hz, 1 H), 4.23 (d, J ) 1.5 Hz, 1 H), 4.67 (dt,
J ) 10.1, 4.7 Hz, 1 H), 7.01-7.39 (m, 10 H), 13C NMR (CD2-
Cl2, 75.5 MHz) δ 23.7 (t′), 24.2 (t′), 26.0 (t′), 27.3 (t′), 33.4 (t′),
47.1 (d′), 59.4 (d′), 84.8 (d′), 121.0 (d′), 123.2 (d′), 129.6 (d′),
147.5 (s′), 174.5 (s′); exact mass m/z calcd for C21H24N2O2
336.1837, found 336.1834.

1240 J . Org. Chem., Vol. 66, No. 4, 2001
Clive et al.
The use of Ph3SnH gave a similar yield. However, it was
found that the separation of the crude mixture was easier than
in the case of Bu3SnH.
(3r,3a r,8a r)-3-(2,2-Dip h en ylh yd r a zin o)-3,3a ,8,8a -t et -
r a h yd r o-2H-in d en o[2,1-b]fu r a n -2-on e (exo-23c), (3r,3a â,-
8a â)-3-(2,2-Dip h en ylh yd r a zin o)-3,3a ,8,8a -tetr a h yd r o-2H-
in d en o[2,1-b]fu r a n -2-on e (en d o-23c) a n d (3a R*,8bS*)-3-
(2,2-Diph en ylh ydr azin o)-3,3a,4,8b-tetr ah ydr o-2H-in den o-
[1,2-b]fu r a n -2-on e (23c′).
a mixture [ca. 1:1.4 (1H NMR)] of two isomers: FTIR (CH2Cl2
1
cast) 1775 cm-1; H NMR (CDCl3, 400 MHz) δ 1.68-2.42 (m,
2 H), 3.18-3.30 (m, 1 H), 3.73-3.89 (m, 1 H), 4.0-4.18 (m, 2
H), 4.42-4.8 (br s, 1 H), 5.98 (d, J ) 4.6 Hz, 0.53 H), 6.21 (d,
J ) 5.5 Hz, 0.37 H), 6.99-7.43 (m, 10 H); 13C NMR (CDCl3,
100.6 MHz) δ 24.4 (t′), 30.3 (t′), 44.8 (d′), 45.0 (d′), 59.1 (d′),
62.4 (d′), 68.0 (t′), 69.4 (t′), 106.9 (d′), 108.2 (d′), 120.6 (d′), 120.8
(d′), 123.4 (d′), 129.5 (d′), 129.6 (d′), 146.9 (s′), 147.2 (s′), 173.0
(s′), 174.0 (s′); exact mass m/z calcd for C18H18N2O3 310.1317,
found 310.1309.
3-Am in od ih yd r o-2(3H)fu r a n on e Hyd r och lor id e (6d ).34
Hydrochloric acid (6 N, 0.8 mL) was added to a solution of 6c
(40 mg, 0.15 mmol) in THF (4 mL), followed by 10% Pd-C (20
mg), and the mixture was shaken under an atmosphere of H2
for 3 h. The mixture was filtered through a small pad of Celite,
which was washed with water, and the combined filtrates were
1
evaporated. The H NMR spectrum of the residue showed the
The general procedure for radical cyclization was followed,
using 23b (0.500 g, 1.15 mmol) in PhMe (70 mL), Bu3SnH (474
µL, 1.76 mmol) in PhMe (10 mL), and AIBN (30 mg, 0.18
mmol) in PhMe (10 mL). The solvent was evaporated and the
residue was covered with 40% EtOAc-hexane and left to stand
for 0.5 h. The precipitate was then filtered off and washed with
40% EtOAc-hexane (2 × 3 mL) to give a first crop of en d o-
23c (70.0 mg, 17%) as a crystalline solid. Evaporation of the
filtrate and flash chromatography of the residue over silica
gel (1.6 cm × 30 cm), using 5% EtOAc-hexane, gave a 1:1.2
mixture (67 mg) of exo-23c and 23c′ (as two isomers), pure
exo-23c (100 mg, 24%) and pure en d o-23c (90 mg, 22%), each
of the three fractions being a crystalline solid.
The fraction containing exo-23c and 23c′ had the following
characteristics: FTIR (CH2Cl2 cast) 1770 cm-1; 1H NMR (CD2-
Cl2, 400 MHz) δ 2.88-2.95 (m, 0.64 H), 3.20-3.50 (m, 2.35
H), 3.69 (dd, J ) 6.0, 1.6 Hz, 0.29 H), 3.95 (t, J ) 1.7 Hz, 0.47
H), 4.15 (d, J ) 5.6 Hz, 0.49 H), 4.31 (dd, J ) 7.9, 1.3 Hz, 0.33
H), 4.62 (d, J ) 2.0 Hz, 0.49 H), 4.72-4.79 (m, 0.61 H), 5.56-
5.63 (m, 0.77 H), 6.03 (d, J ) 7.6 Hz, 0.25 H), 6.85-7.50 (m,
14 H); 13C NMR (CD2Cl2, 100.6 MHz) δ 32.4 (t′), 36.2 (t′), 38.9
(t′), 44.1 (d′), 44.9 (d′), 51.3 (d′), 60.0 (d′), 63.0 (d′), 63.6 (d′),
84.8 (d′), 85.9 (d′), 86.6 (d′), 120.8 (d′), 120.9 (d′), 121.0 (d′),
123.3 (d′), 123.4 (d′), 123.5 (d′), 125.3 (d′), 125.6 (d′), 125.8 (d′),
126.2 (d′), 126.5 (d′), 127.4 (d′), 127.8 (d′), 128.7 (d′), 129.67
(d′), 129.70 (d′), 129.8 (d′), 130.3 (d′), 130.7 (d′), 138.5 (s′), 139.1
(s′), 140.2 (s′), 140.9 (s′), 142.7 (s′), 145.7 (s′), 147.3 (s′), 147.6
(s′), 147.7 (s′), 174.6 (s′), 174.9 (s′), 175.6 (s′); exact mass m/z
calcd for C23H20N2O2 356.1525, found 356.1522.
amino lactone hydrochloride and Ph2NH‚HCl. The residue was
dissolved in water, and acetone was added to produce crystals
(16.5 mg, 81%) of 6d : mp 196-200 °C (decomp), (lit.34 201-
203 °C); 1H NMR (360 MHz, D2O) δ 2.40-2.60 (m, 1 H), 2.79-
2.91 (m, 1 H), 4.45-4.54 (m, 2 H), 4.61 (t, J ) 9.7 Hz, 1 H).
Dih yd r o-2,3-fu r a n d ion e 3-Di(4-m eth oxyp h en yl)h yd r a -
zon e (10d ). DDQ (30.9 mg, 0.1362 mmol) was added to a
stirred solution of 10c (29.8 mg, 0.09 mmol) in CH2Cl2 (2 mL)
containing a small amount of water (0.15 mL). The reaction
was complete within 5 min (TLC control, silica, 40% EtOAc-
hexane). Saturated aqueous NaHCO3 (10 mL) was added, and
the mixture was extracted with CH2Cl2. The organic extract
was washed with brine, dried (Na2SO4), and evaporated. Flash
chromatography of the residue over silica gel (1.7 cm × 32 cm),
using 40% EtOAc-hexane, gave 10d (0.0294 g, 99%) as a
crystalline solid: mp 160-161 °C; FTIR (CH2Cl2 cast) 1759,
1505 cm-1; 1H NMR (CD2Cl2, 400 MHz) δ 2.09 (t, J ) 7.3 Hz,
2 H), 3.81 (s, 6 H), 4.15 (t, J ) 7.3 Hz, 2 H), 6.87-7.19 (m, 8
H); 13C NMR (CD2Cl2, 100.6 MHz) δ 26.9 (t′), 55.9 (q′), 64.7
(t′), 114.6 (d′), 124.8 (d′), 127.9 (s′), 138.0 (s′), 158.2 (s′), 168.9
(s′); exact mass m/z calcd for C18H18N2O4 326.1266, found
326.1275.
tr a n s-2-Br om ocycloh exyl P r op en oa te (25). Acryloyl
chloride (986.6 mg, 10.9 mmol) was added slowly (over ca. 10
min) to a stirred and cooled (0 °C) solution of trans-2-
bromocyclohexanol (17a 29) (970.0 mg, 5.45 mmol), DMAP (18.3
mg, 0.8175 mmol), and Et3N (1.1029 g, 10.9 mmol) in CH2Cl2
(35 mL). Stirring at 0 °C was continued for 2 h, and then
saturated aqueous NaHCO3 (15 mL) was added. The organic
layer was separated, and the aqueous layer was extracted with
CH2Cl2. The combined organic extracts were dried (Na2SO4)
and evaporated. Flash chromatography of the residue over
silica gel (1.7 cm × 35 cm), using 10% EtOAc-hexane, gave
25 (783.1 mg, 62%) as a colorless oil: FTIR (CH2Cl2 cast) l726
cm-1; 1H NMR (CDCl3, 200 MHz) δ 1.13-2.42 (m, 8 H), 3.88-
4.07 (m, 1 H), 4.81-5.02 (m, 1 H), 5.76-5.88 (m, 1 H), 6.08
(ddd, J ) 17.2, 10.3, 1.5 Hz, 1 H), 6.31-6.48 (m, 1 H); 13C NMR
(50.3 MHz, CDCl3) δ 23.2 (t′), 25.4 (t′), 31.0 (t′), 35.5 (t′), 52.6
(d′), 75.8 (d′), 128.4 (d′), 131.0 (t′), 165.0 (s′); exact mass m/z
calcd for C9H1379BrO2 232.0098, found 232.0098.
Exo-23c had the following characteristics: mp 158-160 °C;
1
FTIR (CH2Cl2 cast) 1771 cm-1; H NMR (CDCl3, 400 MHz) δ
3.33 (d, J ) 3.3 Hz, 2 H), 3.97 (t, J ) 1.5 Hz, 1 H), 4.17 (d, J
) 5.8 Hz, 1 H), 4.56 (d, J ) 1.8 Hz, 1 H), 5.59 (dt, J ) 5.8, 3.4
Hz, 1 H), 6.82-7.40 (m, 14 H); 13C NMR (CDCl3, 50.3 MHz) δ
38.6 (t′), 50.9 (d′), 63.4 (d′), 84.6 (d′), 120.5 (d′), 123.3 (d′), 125.0
(d′), 125.4 (d′), 127.6 (d′), 128.5 (d′), 129.6 (d′), 139.7 (s′), 140.3
(s′), 146.9 (s′); 174.9 (s′); exact mass m/z calcd for C23H20N2O2
356.1525, found 356.1519.
En d o-23c had the following characteristics: mp 183-185
°C; FTIR (CH2Cl2 cast) 1761 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 3.21-3.37 (m, 2 H), 4.20 (dd, J ) 8.1, 4.7 Hz, 1 H), 4.34 (dd,
J ) 8.1, 1.5 Hz, 1 H), 4.55 (s, 1 H), 5.17 (t, J ) 4.7 Hz, 1 H),
7.03-7.40 (m, 14 H); 13C NMR (CDCl3, 100.6 MHz) δ 38.6 (t′),
49.6 (d′), 60.6 (d′), 82.0 (d′), 121.5 (d′), 123.7 (d′), 125.0 (d′),
126.9 (d′), 128.4 (d′), 128.9 (d′), 129.5 (d′), 137.1 (s′), 140.9 (s′),
148.0 (s′), 174.5 (s′); exact mass m/z calcd for C23H20N2O2
356.1525, found 356.1518. Irradiation of the Ha 1H NMR signal
for exo-23c caused an NOE of 6% in the signal for Hb and 0%
for the Hc signal; in the case of en d o-23c, the corresponding
values were 6% and 3%, respectively.
(3r,3a r,6a r)- a n d (3r,3a â,6a â)-3-(2,2-Dip h en ylh yd r a -
zin o)tetr a h ydr ofu r o[2,3-b]fu r a n -2(3H)-on e (24c). The gen-
eral procedure for radical cyclization was followed, using 24b
(753.4 mg, 1.942 mmol) in PhMe (120 mL), Bu3SnH (847.8 mg,
2.913 mmol) in PhMe (15 mL), and AIBN (32.0 mg, 0.1942
mmol) in PhMe (15 mL). Flash chromatography of the crude
product over silica gel (1.7 cm × 34 cm), using 50% EtOAc-
hexane, gave 24c (285.0 mg, 47%) as a colorless oil, which was
tr a n s-2-Br om ocycloh exyl Dih yd r oxya ceta te (26). OsO4
(2.5% w/w in t-BuOH, 4.0 mg, 0.016 mmol) was added to a
stirred mixture of acrylate 25 (457.3 mg, 1.97 mmol), water
(2.7 mL), and dioxane (8 mL). After 10 min, the mixture had
become dark brown. NaIO4 (1.264 g, 5.91 mmol) was then
added portionwise over ca. 10 min, and the resulting mixture
was stirred for 6 h. Brine (6.0 mL) was added, and the mixture
was extracted with Et2O. The combined organic extracts were
washed with water and 10% aqueous NaHSO3, dried (Na2SO4),
and evaporated. Flash chromatography of the residue over
silica gel (1.7 cm × 32 cm), using 15% EtOAc-hexane, gave
26 (235.4 mg, ca. 47%, assuming product is totally the
dihydroxy acetate) as a colorless gum, which was used directly
in the next step. The material was mainly the hydrate but
(34) (a) Fischer, E.; Blumenthal, H. Chem. Ber. 1907, 40, 106-113.
(b) Snyder, H. R.; Andreen, J . H.; Cannon, G. W.; Peters, C. F. J . Am.
Chem. Soc. 1942, 64, 2082-2084.

R-(2,2-Diphenylhydrazino)lactones
J . Org. Chem., Vol. 66, No. 4, 2001 1241
contained (1H NMR) a small amount (ca. 5 mol %) of the parent
aldehyde (trans-2-bromocyclohexyl glyoxalate).
added periodically. After the evaporation, a yellow powder was
obtained. This was dissolved in the minimum amount of EtOH,
and Et2O was then added until slight turbidity was observed.
The mixture was kept at 5 °C overnight, to obtain 3136 as a
white crystalline solid, which was recrystallized in the same
way to give 31 (109.2 mg, 48%): mp 249-253 °C [(lit.36b 246
tr a n s-2-Br om ocycloh exyl [N-(1,2,2-Tr ip h en ylet h yl)-
for m im id oyl]for m a te (28). A solution of amine 2735 (2.9326
g, 10.8 mmol) in CH2Cl2 (10 mL) was added to a stirred
solution of 26 (2.512 g, 10.8 mmol) in CH2Cl2 (10 mL). The
mixture was stirred overnight, and then evaporated. Flash
chromatography of the residue over silica gel (4 cm × 32 cm),
using 20% EtOAc-hexane, gave 28 (4.4311 g, 84%) as a
foam: FTIR (CH2Cl2 cast) 1747, 1722 cm-1; 1H NMR (CD2Cl2,
400 MHz) δ 1.24-2.43 (m, 8 H), 3.96-4.15 (m, 1 H), 4.78 (dd,
J ) 10.3, 3.2 Hz, 1 H), 4.90-5.01 (m, 1 H), 5.51 (t, J ) 11 Hz,
1 H), 7.04-7.53 (m, 16 H); 13C NMR (CD2Cl2, 100.6 MHz) δ
23.6 (t′), 23.7 (t′), 25.8 (t′), 25.9 (t′), 31.3 (t′), 31.4 (t′), 36.0 (t′),
36.1 (t′), 52.8 (d′), 52.9 (d′), 58.3 (d′), 58.4 (d′), 77.4 (d′), 77.5
(d′), 79.7 (d′), 79.9 (d′), 126.8 (d′), 127.0 (d′), 127.1 (d′), 127.9
(d′), 128.4 (d′), 128.6 (d′), 128.7 (d′), 128.8 (d′), 128.90 (d′),
128.93 (d′), 129.1 (d′), 129.20 (d′), 129.24 (d′), 140.8 (s′), 140.9
(s′), 141.5 (s′), 141.6 (s′), 142.1 (s′), 153.4 (s′), 153.6 (s′), 161.6
(s′), 161.9 (s′); exact mass m/z calcd for C28H2879BrNO2 489.1303,
found 489.1309.
(3r,3aâ,7aâ)- an d (3r,3ar,7ar)-3-Am in oh exah ydr o-2(3H)-
ben zofu r a n on e Hyd r och lor id e (31). The general procedure
for radical cyclization was followed, using 28 (575.5 mg, 1.18
mmol) in PhMe (75 mL), Bu3SnH (856.1 mg, 2.94 mmol) in
PhMe (10 mL), and AIBN (20 mg, 0.12 mmol) in PhMe (10
mL). After evaporation of the solvent, hydrochloric acid (8 N,
10 mL) was added to the crude product and the solution was
stirred for 1 h. The acidic solution was extracted with CH2-
Cl2, and the aqueous layer was evaporated under reduced
pressure. To facilitate evaporation of HCl, EtOH (100%) was
(decomp)]; FTIR (Microscope) 1775 cm-1 1H NMR (CD3OD,
;
400 MHz) δ 0.98-1.93 (m, 7 H), 2.14 (d, J ) 15.5 Hz, 1 H),
2.74-2.85 (m, 1 H), 4.48 (d, J ) 6.5 Hz, 1 H), 4.68-4.77 (m, 1
H); 13C NMR (CD3OD, 100.6 MHz) δ 20.4 (t′), 22.6 (t′), 23.3
(t′), 27.7 (t′), 39.1 (d′), 56.2 (d′), 78.2 (d′), 173.9 (s′); exact mass
m/z calculated for C8H13NO2 (M - HCl) 155.0946, found
155.0945. The N-acetate was prepared36b and had mp 170-
174 °C (lit.36b 174-175 °C).
Ack n ow led gm en t. We thank the Natural Sciences
and Engineering Research Council of Canada and
Merck Frosst for financial support. S.H. held an NSERC
Undergraduate Summer Award, and V.B. was an under-
graduate at EÄ cole Nationale Supe´rieure de Chime de
Rennes working on a research project at the University
of Alberta.
Su p p or tin g In for m a tion Ava ila ble: NMR spectra of new
compounds and X-ray data for 9b; both experimental proce-
dures and characterization data for 2d , 2e, 2h , 8b, 9b, 14b,
13c; and characterization data for 2f, 2g, 10b, 11b, 13b, 15b,
19b, 20b, 10c, 11c, 13c, 15c, 20c. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O0013655
(36) (a) Cf. Edelson, J .; Pal, P. R.; Skinner, C. G.; Shive, W. J . Am.
Chem. Soc. 1957, 79, 5209-5212. (b) Arbuzov, Yu. A.; Ivanov, V. T.;
Kolosov, M. N.; Ovchinnikov, Yu. A.; Shemyakin, M. M. J . Gen. Chem.
USSR (Engl. Trans.) 1964, 34, 1081-1089.
(35) (a) Smith, H. E.; Willis, T. C. Tetrahedron 1970, 26, 107-118.
(b) Gao, J .; Hu, M.-y.; Chen, J .-x.; Yuan, S.; Chen, W.-x. Tetrahedron
Lett. 1993, 34, 1617-1620.