A New Redundant Rearrangement of Aromatic Ring Fused Cyclic α-Hydroxydithiane Derivatives. Synthesis of Aromatic Ring Fused Cyclic 1,2-Diketones with One-Carbon Ring Expansion

Article abstract of DOI:10.1021/jo990634s

A new reaction involving rearrangement of aromatic ring fused cyclic dithiane alcohol by N-chlorosuccinimide in CH₂Cl₂-H₂O to the corresponding one-carbon ring expanded 1,2-diketone has been developed. A wide range of structurally varied dithiane alcohols have been found to undergo this rearrangement in high yields. The general criteria and reaction mechanism for this rearrangement have also been worked out.

Full text of DOI:10.1021/jo990634s

6380
J . Org. Chem. 1999, 64, 6380-6386
A New Red u n d a n t Rea r r a n gem en t of Ar om a tic Rin g F u sed Cyclic
r-Hyd r oxyd ith ia n e Der iva tives. Syn th esis of Ar om a tic Rin g F u sed
Cyclic 1,2-Dik eton es w ith On e-Ca r bon Rin g Exp a n sion
Brindaban C. Ranu* and Umasish J ana
Department of Organic Chemistry, Indian Association for the Cultivation of Science,
J adavpur, Calcutta - 700 032, India
Received April 14, 1999
A new reaction involving rearrangement of aromatic ring fused cyclic dithiane alcohol by
N-chlorosuccinimide in CH2Cl2-H2O to the corresponding one-carbon ring expanded 1,2-diketone
has been developed. A wide range of structurally varied dithiane alcohols have been found to undergo
this rearrangement in high yields. The general criteria and reaction mechanism for this
rearrangement have also been worked out.
Sch em e 1
In tr od u ction
During a recent investigation we have encountered an
unexpected rearrangement of dithianylcyclobutachro-
manol derivative 1 to 1,2,2a,8,9,9a-hexahydrocyclobuta-
[b][1]benzoxepin-8,9-dione 2 on treatment with mercuric
oxide and fluoroboric acid in aqueous tetrahydrofuran1
(Scheme 1).
This rearrangement is unprecedented and leads to a
unique system incorporating an aromatic ring fused 1,2-
dione unit which is of considerable synthetic importance,
being an active constituent in many natural products,
e.g., carbazoquinocin C, tanshinone1 etc.2 This prompted
us to initiate a systematic investigation to find out the
generality, scope, and reaction pathways of this new
rearrangement. After a detailed study we have been able
to postulate the general criteria and best experimental
conditions for this rearrangement, together with its
possible mechanism, and these results will be presented
here.
substituent at the ring juncture adjacent to hydroxy
carbon and poses two questions: (a) whether the presence
of a fused cyclobutane moiety and an aromatic ring are
indispensable, and (b) whether the ring-oxygen has any
role to play. It also solicits attempts for further improve-
ment of the yield of the rearranged product.
To find out the best experimental conditions, a number
of other reagents such as HgO, BF3 in aq THF; CaCO3,
HgCl2 in aq CH3CN; and N-chlorosuccinimide in CH2-
Cl2-H2O have been tried and among all these, NCS in
CH2Cl2-H2O has been found to be the best. Thus, in a
typical general procedure, the dithiane alcohol (1 mmol)
was stirred with N-chlorosuccinimide (3.5 mmol) in CH2-
Cl2 in the presence of a few drops of water at room
temperature under nitrogen, for a certain period of time
as required to complete the reaction (TLC). CH2Cl2 was
removed, and the residue was extracted with ether.
Evaporation of ether followed by purification by column
chromatography furnished the rearranged diketone. This
procedure is followed for the rearrangement of all dithiane
alcohols. All products including 1,2-diketones have been
properly characterized by IR and 1H and 13C NMR
spectral data and elemental analysis (Experimental
Section).
Resu lts a n d Discu ssion s
A wide range of structurally varied dithiane alcohols
[12, 14, 16, 18, 20, 22, 24, 26, 28] have been incorporated
for this study. These dithiane alcohols have been pre-
pared by the reaction of the corresponding ketones with
2-lithio-1,3-dithiane in THF.3 The ketones were obtained
from suitable precursors primarily by Friedel-Crafts
acylation followed by alkylation by standard procedures4
as delineated in Scheme 2.
Our initial observation of this rearrangement, as
represented in Scheme 1, revealed the requirement of a
(1) Ranu, B. C.; Bhar, S.; Patra, A.; Nayak, N. P.; Mukherjee, M.
Chem. Commun. 1996, 1965.
(2) (a) Tanaka, M.; Shin-Ya, K.; Furihata, K.; Seto, H. J . Antibiot.
1995, 48, 326. (b) Knolker, H.-J .; Frohner, W. Tetrahedron Lett. 1997,
38, 1535. (c) Danheiser, R.; Casebier, D. S.; Loebach, J . L. Tetrahedron
Lett. 1992, 33, 1149. (d) Knolker, H.-J .; Frohner, W. Tetrahedron Lett.
1998, 39, 2537.
(3) Ranu, B. C.; Sarkar, D. C.; Basu, M. K. Tetrahedron 1989, 45,
3107; Chakraborty, R.; Basu, M. K.; Ranu, B. C. Tetrahedron 1992,
48, 8849.
(4) Furniss, B. S.; Hannaford, A. J .; Smith, P. W. G.; Tatchell, A. R.
Vogel’s Textbook of Practical Organic Chemistry, 5th ed.; Longman
Group: Harlow, Essex, England, 1989. Krapcho, A. P. Synthesis 1974,
383. Olson, C. E.; Bader, A. R. Organic Syntheses; Wiley: New York,
1963; Coll. Vol. 4, p 898.
The dithiane alcohol 12 containing a fused cyclopen-
tane ring, when subjected to this procedure, underwent
smooth rearrangement to produce the 1,2-diketone 13 in
high yield (Scheme 3). Obviously this disproves the
absolute necessity of a cyclobutane ring (Scheme 1). On
the other hand, the efficient rearrangement of dithiane
alcohols 14 and 16 eliminates the possibility of any role
10.1021/jo990634s CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/30/1999

Rearrangement of Aromatic Ring Fused Cyclic R-Hydroxydithiane
J . Org. Chem., Vol. 64, No. 17, 1999 6381
Sch em e 2.a P r ep a r a tion of Ar om a tic Rin g F u sed Keton e Su bstr a tes
a
Reagents and conditions: (i) PPA, 100 °C; (ii) LDA, THF, MeI; (iii) AlCl3, reflux; (iv) AlCl3, CH2Cl2, 0 °C; (v) NH2NH2‚H2O, KOH,
diethylene glycol, 180 °C; (vi) MeI, DMF, benzene, reflux; (vii) Br(CH2)4Br, KOBut, benzene, reflux.
of ring oxygen in this rearrangement. The cis,trans-
stereoisomers of 15 and 17 were separated by fractional
crystallization and identified by spectral and analytical
data. The 1H and 13C NMR spectra of cis- and trans-
isomers are conclusively distinct. The structure of 15a
(cis-isomer) was also confirmed by single-crystal X-ray
analysis (Figure 1).5
The dithiane alcohol 18, where the central ring is five-
membered, also underwent rearrangement to provide the
corresponding diketone 19. To find out the necessity of a
fused cyclic unit adjacent to the ring bearing the dithiane
moiety, the dithiane alcohol 20 was subjected to this
rearrangement. Interestingly, the rearranged diketone
21 was isolated, although the yield is relatively low
because of the simultaneous deprotection of the dithiane
alcohol 20 to the corresponding hydroxyaldehyde. As an
obvious extrapolation, the dithiane alcohols 22, 24, 26,
and 28 bearing a five-membered spiro unit, when treated
with N-chlorosuccinimide under identical conditions,
produced the respective diketones 23, 25, 27, and 29 in
good yields. The compound 27 constitutes a unique
(5) Crystal data for 15a . C16H18O2, M ) 242.30. Monoclinic, space
group P21/c, Z ) 4, a ) 14.537(11) Å, b ) 8.149(7) Å, c ) 11.183(6) Å,
â ) 101.79 (5)°, V ) 1297(2) Å3, Dc ) 1.241 mg/m3, µ (Mo-KR) ) 0.80
cm-1. Crystal size ) 0.3 × 0.25 × 0.2 mm, T ) 293(2) K. Siemens R3m/V
diffractomer, λ ) 0.7173 Å, was used to record 1846 reflections (-15
e h e 15, -8 e k e 0, 0 e l e 12). θ Range 2.86 to 22.55°. Unique
reflections 1692 (Rint ) 0.0231) and observed reflections 1389 [I > 2σ-
(I)]. The structure was solved by direct methods (SHELXTL - 93 V
5.03) and refined by full-matrix least-squares on F2 with anisotropic
thermal parameters to non-hydrogen atoms and isotropic thermal
parameters for hydrogen atoms. Final R indices: R1(F) ) 0.0468, wR2-
(F2) ) 0.1277, R1 (all data) ) 0.0595, wR2 (all data) ) 0.1385. Largest
diff. peak and hole ) 0.195 and -0.226 eÅ-3, respectively.

6382 J . Org. Chem., Vol. 64, No. 17, 1999
Ranu and J ana
Sch em e 3.a Rea r r a n gem en ts
a
Reagents and conditions: (i) n-BuLi, 1,3-dithiane, THF, -25 °C; (ii) N-chlorosuccinimide, CH2Cl2, H2O.
system bearing an eight-membered diketone fused with
an aromatic ring and a spiro carbocycle.
Now, to ascertain the requirement of a fused aromatic
ring, a nonaromatic dithiane alcohol 31 was subjected

Rearrangement of Aromatic Ring Fused Cyclic R-Hydroxydithiane
J . Org. Chem., Vol. 64, No. 17, 1999 6383
Exp er im en ta l Section
1
Gen er a l. H NMR and 13C NMR spectra were recorded in
CDCl3 solution at 300 and 75 MHz, respectively. Analyses were
done on a Perkin-Elmer 240C autoanalyzer. Tetrahydrofuran
(THF) was distilled over potassium-benzophenone immedi-
ately before use. Methylene chloride (CH2Cl2) was dried over
P2O5. N-Chlorosuccinimide was used as supplied (E. Merck).
P r ep a r a tion of Keton es. Keton e 3. To polyphosphoric
acid (10 g), prepared by heating a mixture of P2O5 (5 g) and
H3PO4 (2.5 mL) at 100 °C for 5 h, was added a mixture of
phenol (941 mg, 10 mmol) and cyclopentene carboxylic acid
(1.12 g, 10 mmol). The reaction mixture was agitated by
mechanical stirrer at 100 °C for 4.5 h. The reaction mixture
was cooled and quenched by ice-water. The resulting aqueous
suspension was extracted with ether. The ether extract was
washed successively by water, 10% KOH, and brine and dried
over Na2SO4. The extract was evaporated and purified by silica
gel column chromatography to afford the intermediate cyclic
ketone (564 mg, 30%) as a colorless liquid; IR (neat) 1680, 1605
F igu r e 1. X-ray crystal structure of cis-isomer of 15 (15a ).
to this rearrangement and found to furnish only the
deprotected hydroxyaldehyde 32 (Scheme 4). No rear-
rangement has been observed to occur under varied
experimental conditions also. The acyclic dithiane alcohol
34 also did not produce any rearranged diketone; only
the hydroxyaldehyde 35 was obtained. So, from this study
it appears that this rearrangement is a general one for
aromatic ring fused cyclic dithiane alcohols bearing no
hydrogen at the position R to the carbon containing
hydroxy and dithiane moieties. A possible mechanism has
been delineated in Scheme 5. Obviously, the key step is
the conversion of the intermediate II to III involving the
migration of bond “a”.6 This bond migration is greatly
facilitated by the electron density on the adjacent carbon,
which plays a vital role in guiding this rearrangement.
Thus, this rearrangement does not occur at all when
there is no substitution at this center7 and proceeds
marginally with monosubstitution (1c to 2c). When this
rearrangement is carried out with N-chlorosuccinimide
in dry CH2Cl2, the intermediate monoketone 36 (IR 1680
cm-1) has been isolated in high (75%) yield. Treatment
of 36 with NCS in H2O produced the diketone 25 almost
quantitatively. Formation of the monoketone 36 certainly
substantiates the migration of bond “a” and rules out aryl
migration. Similar observations were also made with
another substrate 1b. Obviously, the presence of H2O in
the reaction medium from the start pushed the reaction
to the final product in a single operation.
1
cm-1; H NMR δ 1.74-2.20 (m, 6H), 2.69-2.73 (m, 1H), 4.92
(t, J ) 3 Hz, 1H), 6.91 (d, J ) 9 Hz, 1H), 6.98 (t, J ) 9 Hz,
1H), 7.44 (t, J ) 9 Hz, 1H), 7.87 (d, J ) 9 Hz, 1H); 13C NMR
δ 22.4, 27.5, 33.0, 51.1, 83.3, 118.0, 119.1, 121.2, 127.0, 136.6,
160.6, 194.6. Anal. Calcd for C12H12O2: C, 76.57; H, 6.43.
Found: C, 76.65; H, 6.66.
A solution of the ketone, prepared in the earlier step, (300
mg, 1.59 mmol) in THF (2 mL) was added to a stirred solution
of LDA in THF at -78 °C under argon. The reaction mixture
was slowly warmed to -25 °C and stirred at that temperature
for 1.5 h. The temperature of the reaction mixture was again
brought down to -78 °C and HMPA (2 mL) followed by methyl
iodide (0.31 mL, 5 mmol) was added dropwise. The reaction
mixture was allowed to attain room temperature and left
overnight. After quenching with ice cold water, the reaction
mixture was extracted with ether. The ether extract was
washed successively by water and brine and dried over Na2-
SO4. The extract was evaporated, and the residue was purified
by silica gel column chromatography to furnish ketone 3 (241
mg, 75%) as a colorless viscous oil; IR (neat) 1680, 1600 cm-1
;
1H NMR δ 1.20 (s, 3H), 1.58-2.17 (m, 6H), 4.55 (d, J ) 3.3
Hz, 1H), 6.85 (d, J ) 7.5 Hz, 1H), 6.98 (t, J ) 7.5 Hz, 1H),
7.44 (t, J ) 7.5 Hz, 1H), 7.88 (d, J ) 7.5 Hz, 1H); 13C NMR δ
16.9, 19.2, 30.9, 33.7, 52.1, 87.9, 117.9, 121.1, 121.5, 127.3,
135.7, 159.6, 196.5. Anal. Calcd for C13H14O2: C, 77.20; H, 6.98.
Found: C, 77.39; H, 6.70.
Keton e 4. To a stirred solution of lactone (1.40 g, 10 mmol)
in dry benzene (50 mL) was added aluminum chloride (3.99 g,
30 mmol) over a period of 15 min. The reaction mixture was
then heated under reflux for 10 h. It was then cooled to room
temperature and poured into crushed ice followed by acidifica-
tion with concentrated HCl. The product was extracted with
ether, and the ether extract was washed successively by water,
saturated NaHCO3 solution, and brine and dried over Na2SO4.
Evaporation of solvent and purification of the residue by silica
gel column chromatography provided the intermediate cyclic
ketone (1.44 g, 72%) as a solid (mp 100-103 °C); IR (KBr)
1680, 1600 cm-1; 1H NMR δ 1.39-1.67 (m, 9H), 2.69-2.71 (m,
1H), 2.96-3.03 (m, 2H), 7.21-7.31 (m, 2H), 7.46 (dt, J ) 9, 3
Hz, 1H), 8.03 (dd, J ) 9, 3 Hz, 1H); 13C NMR δ 23.4, 23.7,
25.3, 28.82, 33.8, 35.7, 48.2, 126.4, 127.1, 129.2, 131.7, 133.3,
142.8, 200.3. Anal. Calcd for C14H16O: C, 83.96; H, 8.05. Found:
C, 83.98; H, 8.16.
Con clu sion
This rearrangement of aromatic ring fused cyclic
dithiane alcohols by N-chlorosuccinimide to the one-
carbon ring expanded 1,2-diketone constitutes a very
novel fundamental reaction. It makes an easy access to
the basic skeleton of many complex natural products,2
including aryl taxoids.8 The reaction is simple, general,
fast, and high yielding. The presence of two distinct keto
carbonyl functionalities and the aromatic ring with high
potential for various manipulations make this system
more synthetically useful. Further investigations to
broaden the scope of this rearrangement will constitute
our next endeavor.
Methylation of this intermediate ketone following the same
procedure as in the preparation of 3 produced the ketone 4 as
a colorless liquid (76%, as a 1:1 mixture of cis-trans isomers);
1
IR (neat) 1675, 1605 cm-1; H NMR δ 1.05 (s, 1.5 H), 1.17 (s,
1.5 H), 1.25-1.97 (m, 9H), 2.63-2.73 (m, 2H). Anal. Calcd for
C
15H18O: C, 84.06; H, 8.47. Found: C, 84.36; H, 8.63.
(6) This type of bond migration is very facile and follows the
conventional migratory aptitude: Carruthers, W. Modern Methods of
Organic Synthesis, 3rd ed.; Cambridge University Press: New York,
1996.
(7) The corresponding dithiane alcohols from 1-indanone and 1-tet-
ralone did not undergo this rearrangement.
Keton e 5. To a cold (0 °C) stirred solution of anisole (2.40
g, 20 mmol) and AlCl3 (6.66 g, 50 mmol) in dry CH2Cl2 (25
mL), was added 1,2-cis-cyclohexanecarboxylic anhydride (3.08
g, 20 mmol) in CH2Cl2 (6 mL). The mixture was vigorously
stirred, and the temperature of the reaction was maintained
at 0 °C for 3 h; then the reaction mixture was kept frozen
(8) Nicolaou, K. C.; Claiborne, C. F.; Paulvannan, K.; Postema, M.
H. D.; Guy, R. K. Chem. Eur. J . 1997, 3, 399.

6384 J . Org. Chem., Vol. 64, No. 17, 1999
Ranu and J ana
Sch em e 4a
a
Reagents and conditions: (i) Br(CH2)4Br, KOBut, benzene, reflux; (ii) n-BuLi, 1,3-dithiane, THF, -25 °C; (iii) N-chlorosuccinimide,
CH2Cl2, H2O.
(d, J ) 2.7 Hz, 1H); 13C NMR δ 25.4, 25.8, 26.0, 34.0, 36.5,
40.3, 51.8, 55.5, 109.2, 121.4, 129.7, 133.1,136.1, 158.2, 199.8.
Anal. Calcd for C15H18O2: C, 78.23; H, 7.88. Found: C, 78.30;
H, 7.95.
Sch em e 5
Methylation of this intermediate ketone was performed by
LDA and methyl iodide by the same procedure as in the
preparation of 3. Ketone 5 was obtained in 80% yield as a pale
1
yellow liquid [cis-trans (1:1)]; IR (neat) 1670, 1600 cm-1; H
NMR δ 1.05 (s, 1.5 H), 1.18 (s, 1.5 H), 1.23-1.96 (m, 9H), 2.57-
2.70 (m, 2H), 3.81 (s,1.5 H), 3.82 (s, 1.5 H), 7.00-7.10 (m, 2H),
7.52 (m, 1H). Anal. Calcd for C16H20O2: C, 78.65; H, 8.25.
Found: C, 78.92; H, 8.43.
Keton e 6. To a solution of 1-cyclohexenoyl chloride (1.44 g,
10 mmol) in dry benzene (30 mL) was added AlCl3 (2.66 g, 20
mmol) over a period of 10 min. The mixture was then refluxed
for 5 h, cooled to room temperature, and poured into ice water
followed by acidification with concentrated HCl. The product
was extracted with ether, and the ether extract was succes-
sively washed with water and brine and dried over Na2SO4.
The solvent was evaporated off, and the residue was purified
by silica gel column chromatography to produce a cyclic ketone
(1.21 g, 65%) as a colorless liquid; IR (neat) 1705, 1600 cm-1
;
1H NMR δ 1.14-2.10 (m, 8H), 2.69-2.75 (m, 1H), 3.32-3.39
(m, 1H), 7.15-7.74 (m, 4H); 13C NMR δ 22.4, 22.6, 23.1, 31.3,
38.7, 48.4, 123.8, 123.8, 124.0, 127.3, 135.5, 158.3, 207.8. Anal.
Calcd for C13H14O: C, 83.83; H, 7.58. Found: C, 83.90; H, 7.62.
Ketone 6 was then obtained by methylation of this ketone
following the same procedure as mentioned earlier, as a
1
colorless liquid (72%); IR (neat) 1710, 1605 cm-1; H NMR δ
overnight. The whole mass was poured into ice-water followed
by acidification with concentrated HCl. The product was
extracted with CH2Cl2, and the organic layer was washed
successively by water and brine and dried over Na2SO4. The
extract was evaporated, and the solid residue was crystallized
to produce the corresponding keto acid (4.72 g, 90%), mp 105
1.22 (s, 3H), 1.42-1.96 (m, 8H), 3.00-3.02 (m, 1H), 7.34-7.75
(m, 4H); 13C NMR δ 21.0, 21.1, 26.2, 31.5, 45.7, 49.6, 124.4,
127.2, 134.3, 135.2, 155.7, 210.9. Anal. Calcd for C14H16O: C,
83.96; H, 8.05. Found: C, 84.02; H, 8.35.
Keton e 7. A solution of indanone (3.96 g, 30 mmol) in
benzene (20 mL) was added dropwise to a stirred suspension
of NaH (3.65 g, 152 mmol) in benzene (30 mL), and stirring
was continued for 5 h. To this solution was added dry DMF
(20 mL), and the mixture was left overnight. Next day the
reaction mixture was cooled to 0 °C, and methyl iodide (1.77
g, 12.46 mmol) was added dropwise and heated to reflux for 8
h. Again, another batch of methyl iodide (1.77 g, 12.46 mmol)
was added and reflux was continued for another 8 h. Then
the mixture was cooled to 0 °C and quenched by ice-water.
The product was extracted with ether, and the ether extract
was washed successively by water and brine and dried over
Na2SO4. The extract was evaporated, and the crude residue
was purified by vacuum distillation (120 °C/15-20 mm) to
afford the 2,2-dimethylindanone 7 as a liquid (3.12 g, 65%);
°C; IR (KBr) 3600-3500, 1710-1720,1600 cm-1 1H NMR δ
;
1.28-2.25 (m, 9H), 2.64-2.68 (m, 1H), 3.88 (s, 3H), 6.91 (dt, J
) 9, 3 Hz, 2H), 7.85 (dt, J ) 9, 3 Hz, 2H). This keto acid (4 g,
15.26 mmol) was added to a hot solution of KOH (4 g, 41.3
mmol) in diethylene glycol (20 mL) followed by hydrazine
hydrate (1.5 mL). The mixture was heated at 180 °C under
stirring with continuous removal of water formed over a period
of 2 h. After being cooled, it was poured into ice-water and
acidified by HCl. The product was extracted with ether, and
the ether extract was successively washed by water and brine
and dried over Na2SO4. The extract was evaporated, and the
solid residue was crystallized to afford the intermediate acid
(2.87 g, 76%), mp 90-92 °C; IR (KBr) 3500-3600, 1700-1710,
1600 cm-1; 1H NMR δ 0.85-2.28 (m, 11H), 2.79-2.81 (m, 1H),
3.77 (s, 3H), 6.81 (d, J ) 9 Hz, 2H), 7.07 (d, J ) 9 Hz, 2H).
This acid (1 g, 4.02 mmol) was then cyclized by stirring in PPA
for 2 h at 90 °C. Usual workup and purification by silica gel
column chromatography yielded the corresponding cyclic
ketone (656 mg, 71%) as a solid, mp 109-110 °C; IR (KBr)
1670, 1600 cm-1; 1H NMR δ 1.19-2.11 (m, 9H), 2.37-2.41 (m,
1H), 2.62-2.85 (m, 2H), 3.81 (s, 3H), 7.00-7.12 (m, 2H), 7.49
IR (neat) 1710, 1600 cm-1 1H NMR δ 1.23 (s, 6H), 3.00 (s,
;
2H), 7.36 (m, 2H), 7.56 (t, J ) 7.5 Hz, 1H), 7.76 (d, J ) 7.5
Hz, 1H); 13C NMR δ 26.9, 44.5, 47.1, 126.1, 128.3, 129.1, 136.5,
153.9, 213.2. Anal. Calcd for C11H12O: C, 82.46; H, 7.50. Found:
C, 82.62; H, 7.64.
Keton e 8. A solution of indanone (462 mg, 3.5 mmol) in
benzene (2 mL) was added to a magnetically stirred suspension

Rearrangement of Aromatic Ring Fused Cyclic R-Hydroxydithiane
of potassium tert-butoxide (897.6 mg, 8 mmol) in benzene (20
J . Org. Chem., Vol. 64, No. 17, 1999 6385
Dithiane alcohol 18, yield 70%, viscous oil; IR (neat) 3600-
mL) under nitrogen, and the mixture was refluxed for a period
of 2.5 h. After being cooled to room temperature, this was
quenched with ice-water and extracted with ether. The ether
extract was washed throughly with water and brine and dried
over Na2SO4. Evaporation of solvent and purification by silica
gel column chromatography afforded pure spiro ketone 8 (438
mg, 85%) as an oil; IR (neat) 1705, 1600 cm-1; 1H NMR δ 1.58-
2.00 (m, 8H), 3.02 (s, 2H), 7.34-7.42 (m, 2H), 7.56 (t, J ) 6
Hz, 1H), 7.75 (d, J ) 9 Hz, 1H); 13C NMR δ 25.6, 38.3, 43.0,
56.9, 123.8, 126.0, 126.3, 127.2, 134.5, 152.7, 211.0. Anal. Calcd
for C13H14O: C, 83.83; H, 75.80. Found: C, 83.95; H, 77.79.
This procedure is followed for the preparation of spiroke-
tones 9-11, 30, 33. Ketone 9, oil (80%), IR (neat) 1680, 1600
cm-1; 1H NMR δ 1.51-1.55 (m, 2H), 1.69-1.78 (m, 4H), 2.03-
2.14 (m, 4H), 2.98 (t, J ) 6.2 Hz, 2H), 7.20 (d, J ) 7.65 Hz,
1H), 7.28 (t, J ) 7.70 Hz, 1H), 7.44 (dt, J ) 7.4, 1.3 Hz, 1H),
8.04 (d, J ) 7.78 Hz, 1H); 13C NMR δ 25.9, 27.0, 35.6, 53.6,
126.9, 128.3, 133.3, 144.0, 202.9. Anal. Calcd for C14H16O: C,
83.96; H, 8.03. Found: C, 83.90; H, 8.00.
3300, 1600, 1040 cm-1; 1H NMR δ 1.43 (s, 3H), 1.64-2.16 (m,
10H), 2.53-2.97 (m, 5H), 3.37 (s, 1H), 4.51 (s, 1H), 7.08-7.53
(m, 4H); 13C NMR δ 16.8, 21.0, 22.1, 22.9, 25.6, 30.4, 30.7,
30.84, 46.1, 51.0, 57.5, 86.0, 121.9, 125.0, 126.1, 128.5, 128.6,
144.3. Anal. Calcd for C18H24OS2: C, 67.45; H, 7.55. Found: C,
67.90; H, 7.95.
Dithiane alcohol 20, yield 80%, solid, mp 100-102 °C; IR
(KBr) 3600-3400, 1600, 1210 cm-1; H NMR δ 0.95 (s, 3H),
1
1.30 (s, 3H), 1.65-1.87 (m, 2H), 2.40-3.16 (m, 7H), 4.38 (s,
1H), 7.08-7.18 (m, 3H), 7.40 (d, J ) 2.1 Hz, 1H); 13C NMR δ
22.0, 25.6, 26.8, 30.3, 31.0, 46.2, 48.0, 58.1, 86.1, 124.9, 125.6,
126.3, 128.7, 141.9, 143.8. Anal. Calcd for C15H20OS2: C, 64.24;
H, 7.19. Found: C, 64.41; H, 7.32.
Dithiane alcohol 22, yield 75%, solid, mp 102 °C; IR (KBr)
3500-3300, 1600, 1215 cm-1; 1H NMR δ 1.58-2.00 (m, 10H),
2.67-2.94 (m, 4H), 3.13 (s, 2H), 4.47 (s, 1H), 7.17-7.25 (m,
3H), 7.51 (m, 1H); 13C NMR δ 22.4, 23.8, 25.5, 30.0, 30.6, 31.8,
34.4, 43.3, 58.2, 60.1, 85.1, 124.3, 124.9, 126.1, 128.6, 141.9,
144.3. Anal. Calcd for C17H22OS2: C, 66.62; H, 7.24. Found: C,
66.80; H, 7.32.
Ketone 10, viscous oil, yield 78%; IR (neat) 1660, 1600 cm-1
;
1H NMR δ 1.50-1.88 (m, 10H), 2.08 (t, J ) 6 Hz, 2H), 2.76 (t,
J ) 6 Hz, 2H), 3.80 (s, 3H), 6.63 (s, 1H), 6.75 (d, J ) 9 Hz,
1H), 7.34 (d, J ) 9 Hz, 1H); 13C NMR δ 24.1, 25.2, 33.5, 35.2,
37.3, 55.3, 57.9, 111.3, 114.2, 129.7, 134.0, 134.4, 161.5, 213.8.
Anal. Calcd for C16H20O2: C, 78.65; H, 8.25. Found: C, 78.93;
H, 8.34.
Dithiane alcohol 24, yield 82%, solid, mp 57-59 °C; IR (KBr)
3600-3300, 1600, 1210 cm-1; 1H NMR δ 1.19-2.94 (m, 19H),
4.51 (s, 1H), 7.02-7.07 (m, 1H), 7.15-7.22 (m, 2H), 7.66-7.70
(m, 1H); 13C NMR δ 25.3, 25.5, 25.8, 26.0, 30.8, 31.4, 31.5, 33.4,
34.5, 51.3, 59.6, 77.9, 125.0, 126.5, 127.3, 128.0, 137.1, 139.8.
Anal. Calcd for C18H24OS2: C, 67.45; H, 7.55. Found: C, 67.55;
H, 7.74.
Dithiane alcohol 26, yield 80%, solid, mp 144-146 °C; IR
(KBr) 3600-3500, 1605, 1260 cm-1; 1H NMR δ 1.25-2.93 (m,
21H), 3.78 (s, 3H), 5.41 (s, 1H), 6.63 (s, 1H), 6.70 (d, J ) 8.70
Hz, 1H), 7.62 (d, J ) 8.7 Hz, 1H); 13C NMR δ 23.1, 23.9, 25.0,
25.3, 30.3, 31.6, 33.0, 35.8, 37.1, 37.7, 53.2, 54.9, 55.0, 82.2,
109.3, 116.9, 128.2, 136.2, 139.6, 158.3. Anal. Calcd for
Ketone 11, thick oil, yield 85%; IR (neat) 1680 cm-1; 1H NMR
δ 1.49-1.78 (m, 8H), 2.10 (t, J ) 6 Hz, 2H), 3.02 (t, J ) 6 Hz,
2H), 7.03 (d, J ) 5.1 Hz, 1H), 7.36 (d, J ) 5.1 Hz, 1H); 13C
NMR δ 23.0, 25.6, 43.7, 36.5, 52.6, 123.1, 125.5, 136.1, 154.0,
197.6. Anal. Calcd for C12H14OS: C, 69.86; H, 6.84. Found: C,
70.10; H, 7.18.
1
Ketone 30, oil (62%), IR (neat) 1700 cm-1; H NMR δ 1.17
C
20H28O2S2: C, 65.89; H, 7.74. Found: C, 65.92; H, 7.85.
(s, 3H), 1.21 (s, 3H), 1.27-2.18 (m, 2H).
Dithiane alcohol 28, yield 81%, solid, mp 110 °C; IR (KBr)
Ketone 33, yield 85%, liquid; IR (neat) 1680 cm-1; 1H NMR
δ 1.42 (s, 3H), 1.63-1.73 (m, 6H), 2.30-2.34 (m, 2H), 7.40-
7.47 (m, 3H), 7.85-7.88 (m, 2H).
3600-3300, 1080 cm-1; 1H NMR δ 1.29-1.93 (m, 12H), 2.47-
2.89 (m, 7H), 4.55 (s, 1H), 7.07 (d, J ) 6 Hz, 1H), 7.16 (d, J )
6 Hz, 1H); 13C NMR δ 21.7, 25.4, 25.5, 26.0, 31.56, 31.7, 32.0,
32.9, 33.6, 51.7, 59.7, 77.3, 122.0, 126.3, 138.6, 139.1. Anal.
Calcd for C16H22OS3: C, 58.85; H, 6.79. Found: C, 58.92; H,
7.12.
P r ep a r a tion of Dith ia n e Alcoh ols 12, 14, 16, 18, 20, 22,
24, 26, 28, 31, 34. Dith ia n e Alcoh ol 12. To a stirred solution
of 1,3-dithiane (180 mg, 1.5 mmol) in dry THF (3 mL) was
added n-BuLi (1 mL, 1.3 mmol, 1.3 M in hexane) dropwise at
-25 °C, and stirring was continued at that temperature for
1.5 h. Then the mixture was cooled to -78 °C, and the ketone
3 (202 mg, 1 mmol) in THF (2 mL) was added dropwise. The
tempeature of the reaction mixture was again increased to -25
°C and kept at this temperature for additional 2.5 h. Then
the reaction mixture was slowly allowed to attain room
temperature and left overnight. After quenching the reaction
mixture with ice-water, the product was extracted with ether.
The ether extract was washed successively by water and brine
and dried over Na2SO4. Evaporation of the solvent and
purification by silica gel column chromatography furnished the
dithiane alcohol 12 (238.6 mg, 74%) as a solid (mp 124 °C); IR
Dithiane alcohol 31, thick oil, yield 55%, IR (neat) 3600-
3400 cm-1; 1H NMR δ 1.01 (s, >3H), 1.27 (s, >3H), 1.32-1.74
(m, 23H), 2.58 (s, 1H), 2.85-3.00 (m, 4H), 4.36 (s, >1H), 4.42
(s, >1H).
Dithiane alcohol 34, thick oil, yield 80%, IR (neat) 3500-
3300, 1603 cm-1; 1H NMR δ 1.18 (s, 3H), 1.38-2.08 (m, 10H),
2.81-2.98 (m, 5H), 4.80 (s, 1H), 7.26-7.32 (m, 3H), 7.65-7.68
(m, 2H).
Rea r r a n gem en t of Dith ia n e Alcoh ols to th e Cor r e-
sp on d in g 1,2-Dik eton es 13, 15, 17, 19, 21, 23, 25, 27, 29.
Dik eton e 13. To a stirred mixture of dithiane alcohol 12 (100
mg, 0.31 mmol) in CH2Cl2 (4.5 mL) and water (0.5 mL) was
added N-chlorosuccinimide (145 mg, 1.08 mmol) under nitro-
gen. During the addition of N-chlorosuccinimide, a transient
red color appeared for a few seconds. Stirring was continued
for 2 h till completion of the reaction (TLC). The reaction
mixture was then extracted with ether. The ether extract was
washed successively with water and brine and dried over Na2-
SO4. Evaporation of solvent and purification by silica gel
column chromatography afforded the corresponding 1,2-dike-
tone 13 (63.52 mg, 89%) as a light yellow liquid; IR (neat) 1720,
1
(KBr) 3500-3400, 1600 cm-1; H NMR δ 1.20 (s, 3H), 1.54-
2.10 (m, 9H), 2.65-2.82 (m, 4H), 4.47 (s, 1H), 4.92 (d, J ) 3.3
Hz, 1H), 6.79 (d, J ) 8.1 Hz, 1H), 6.94 (t, J ) 7.2 Hz, 1H),
7.23 (dt, J ) 7.8, 1.8 Hz, 1H), 7.57 (dd, J ) 7.8, 1.8 Hz, 1H);
13C NMR δ 19.0, 19.7, 25.1, 29.4, 30.0, 33.4, 33.6, 49.6, 56.6,
75.2, 84.7, 116.1, 119.5, 123.4, 126.9, 129.4, 153.7. Anal. Calcd
for C17H22O2S2: C, 63.32; H, 6.88. Found: C, 63.12; H, 6.84.
Dithiane alcohol 14, yield 72%, solid, mp 106-109 °C, IR
1
(KBr) 3500-3300, 1600 cm-1; H NMR (as a mixture or cis-
1
1670, 1600 cm-1; H NMR δ 1.25 (s, 3H), 1.52-2.20 (m, 5H),
trans isomers) δ 0.86 (s, 1.5 H), 1.30 (s, 1.5 H), 1.37-1.87 (m,
11H), 2.39-2.95 (m, 6H), 3.11 (s, 1H), 4.64 (s, 0.5 H), 4.74 (s,
0.5 H), 7.09-7.25 (m, 3H), 7.65-7.70 (m, 1H). Anal. Calcd for
2.63-2.72 (m, 1H), 4.35 (t, J ) 3.6 Hz, 1H), 7.08 (d, J ) 66.9
Hz, 1H), 7.16 (t, J ) 7.5 Hz, 1H), 7.55 (dt, J ) 7.5, 1.8 Hz,
1H), 7.97 (dd, J ) 7.8, 1.5 Hz, 1H); 13C NMR δ 21.8, 22.9, 31.3,
33.2, 59.5, 93.5, 121.9, 124.0, 124.7, 129.3, 136.5, 163.2, 194.5,
204.9. Anal. Calcd for C14H14O3: C, 73.03; H, 6.13. Found: C,
73.09; H, 6.21.
C
19H26OS2: C, 68.22; H, 7.83. Found: C, 68.06; H, 7.84.
Dithiane alcohol 16, yield 75%, viscous oil, IR (neat) 3600-
3200, 1610, 1210 cm-1; 1H NMR (as mixture of stereoisomers)
δ 0.85 (s, 1.5 H), 1.19 (s, 1.5 H), 1.34-1.93 (m, 10H), 2.26-
2.30 (m, 1H), 2.63-2.86 (m, 6H), 3.81 (s, 3H), 4.62 (s, 0.5 H),
4.70 (s, 0.5 H), 6.76-7.01 (m, 2H), 7.20-7.25 (m, 1H). Anal.
Calcd for C20H28O2S2: C, 65.89; H, 7.74. Found: C, 65.49; H,
7.40.
Diketone 15, yield 90%, solid, was separated by fractional
crystallization (ether-petroleum ether mixture) to give pure
cis-15a and trans-15b isomers.
1
15a (cis), mp 108 °C; IR (KBr) 1700, 1665, 1595 cm-1; H
NMR δ 1.40 (s, 3H), 1.49-1.86 (m, 8H), 2.06-2.09 (m, 1H),

6386 J . Org. Chem., Vol. 64, No. 17, 1999
Ranu and J ana
2.78 (d, J ) 15 Hz, 1H), 3.15 (q, J ) 9 Hz, 1H), 7.24-7.36 (m,
2H), 7.46 (t, J ) 7.5 Hz, 1H), 7.90 (d, J ) 7.8 Hz, 1H); 13C
NMR δ 21.0, 21.1, 21.7, 27.3, 29.3, 39.0, 42.3, 47.4, 126.8, 129.0,
130.3, 133.4, 133.6, 145.7, 198.8, 212.9. Anal. Calcd for
25.6, 26.2, 33.4, 35.2, 55.9, 56.5, 113.2, 116.4, 127.4, 131.6,
145.2, 165.4, 196.9, 214.9. Anal. Calcd for C17H20O3: C, 74.97;
H, 7.40. Found: C, 75.15; H, 7.51.
Diketone 29, yield 82%, solid, mp 45 °C; IR (KBr) 1690,
1675, 1550 cm-1; 1H NMR δ 1.45-1.71 (m, 6H), 2.15-2.32 (m,
4H), 3.05-3.09 (m, 2H), 7.07 (d, J ) 6 Hz, 1H), 7.38 (d, J ) 6
Hz, 1H); 13C NMR δ 25.4, 27.0, 35.5, 39.2, 57.6, 124.0, 127.9,
135.9, 157.5, 191.3, 209.3. Anal. Calcd for C13H14O2S: C, 66.64;
H, 6.02. Found: C, 60.80; H, 6.34.
C
16H18O2: C, 79.31; H, 7.49. Found: C, 79.36; H, 7.39.
1
15b (trans), mp 92 °C; IR (KBr) 1700, 1665, 1595 cm-1; H
NMR δ 1.25 (s, 3H), 1.33-1.83 (m, 8H), 2.13-2.16 (m, 1H),
2.70 (d, J ) 18 Hz, 1H), 3.13 (q, J ) 9 Hz, 1H), 7.24 (t, J ) 6
Hz, 1H), 7.31 (t, J ) 6 Hz, 1H), 7.44 (t, J ) 6 Hz, 1H), 7.73 (d,
J ) 9 Hz, 1H); 13C NMR δ 12.0, 20.0, 25.9, 28.6, 34.3, 38.6,
43.3, 49.3, 126.8, 129.0, 130.3, 133.0, 133.9, 143.5, 200.8, 213.0.
Anal. Calcd for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.38;
H, 7.52.
Tr ea tm en t of Dith ia n e Alcoh ol 31 w ith NCS. The
alcohol 31 on similar treatment with NCS as in other rear-
rangement reactions produced the hydroxyaldehyde 32 as a
1
viscous oil (90%); IR (neat) 3600-3400, 1715, 1560 cm-1; H
Diketone 17, yield 92%, solid, trans-isomer was obtained
NMR δ 0.96 (s, >3H), 1.04 (s, >3H), 1.40-2.46 (m, 21H), 3.45
(broad 1H), 10.14 (s, >1H), 10.28 (s, >1H).
1
pure, mp 102 °C; IR (KBr) 1700, 1670, 1600 cm-1; H NMR δ
1.21 (s, 3H), 1.45-1.80 (m, 8H), 2.06-2.12 (m, 1H), 2.61 (d, J
) 18 Hz, 1H), 3.03 (q, J ) 12 Hz, 1H), 3.79 (s, 3H), 6.96-7.17
(m, 3H); 13C NMR δ 12.0, 20.0, 25.9, 28.6, 34.3, 42.7, 43.6, 49.3,
55.6, 111.4, 120.8, 131.7, 134.5, 134.9, 158.2, 200.7, 212.7.
Anal. Calcd for C17H20O3: C, 74.97; H, 7.40. Found: C, 74.69;
H, 7.38.
Tr ea tm en t of Dith ia n e Alcoh ol 34 w ith NCS. This
alcohol also produced the hydroxyaldehyde 35 as a viscous oil
(89%), IR (neat) 3600-3200, 1710, 1605 cm-1; 1H NMR δ 1.02
(s, 3H), 1.23-1.91 (m, 8H), 3.87 (s, 1H), 7.26-7.39 (m, 3H),
7.59 (d, J ) 9 Hz, 2H).
Isola tion of In ter m ed ia te 36. To a stirred solution of
dithiane alcohol 24 (160 mg, 5 mmol) in dry CH2Cl2 (3.5 mL)
was added N-chlorosuccinimide (80 mg, 6 mmol) under nitro-
gen. During the addition of N-chlorosuccinimide, a transient
red color have developed. The mixture was stirred for 15 min,
and after that CH2Cl2 was removed under vacuum. The residue
was extracted with ether. Evaporation of ether followed by
purification by silica gel column chromatography afforded the
R-keto dithiane derivative 36 (119 mg, 75%) as a solid (mp
Diketone 19, yield 80%, yellow viscous oil, IR (neat) 1720,
1
1670, 1600 cm-1; H NMR δ 1.15 (s, 3H), 1.23-2.05 (m, 8H),
2.50 (d, J ) 12 Hz, 1H), 7.35-7.44 (m, 2H), 7.64 (t, J ) 9 Hz,
1H), 8.09 (d, J ) 9 Hz, 1H); 13C NMR δ 22.5, 25.9, 26.2, 33.9,
39.0, 51.1, 51.2, 127.4, 129.1, 129.3, 131.1, 135.4, 148.7, 181.3,
199.5. Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found :C,
78.98; H, 7.14.
Diketone 21, yield 65%, yellow liquid; IR (neat) 1720, 1680,
1
1600 cm-1; H NMR δ 1.31 (s, 6H), 3.18 (s, 2H), 7.33 (d, J )
123-124 °C); IR (KBr) 1680, 1420, cm-1 1H NMR δ 1.01-
;
7.8 Hz, 1H), 7.42 (t, J ) 7.5 Hz, 1H), 7.62 (t, J ) 7.5 Hz, 1H),
8.08 (d, J ) 7.8 Hz, 1H); 13C NMR δ 21.7, 21.8, 43.0, 47.5,
126.6, 129.4, 129.5, 133.4, 135.8, 142.1, 183.0, 200.3. Anal.
Calcd for C12H12O2: C, 76.57; H, 6.43. Found: C, 76.70; H, 6.75.
Diketone 23, yield 75%; yellow liquid; IR (neat) 1710, 1680,
1600 cm-1; 1H NMR δ 1.30-1.63 (m, 6H), 2.24-2.32 (m, 2H),
3.29 (s, 2H), 7.39 (d, J ) 6.5 Hz, 1H), 7.49 (t, J ) 6.5 Hz, 1H),
7.64 (t, J ) 6.5 Hz, 1H), 8.13 (d, J ) 6.5 Hz, 1H); 13C NMR δ
25.6, 36.9, 41.7, 58.5, 127.6, 129.1, 129.3, 135.1, 142.9, 183.6,
198.9. Anal. Calcd for C14H14O2: C, 78.48; H, 6.59. Found: C,
78.50; H, 6.80.
Diketone 25, yield 70%, solid, mp 52-54 °C; IR (KBr) 1700,
1660, 1600 cm-1; 1H NMR δ 1.41-1.50 (m, 2H), 1.64-1.69 (m,
4H), 2.07-2.11 (m, 2H), 2.28-2.32 (m, 2H), 2.94-2.98 (m, 2H),
7.20-7.48 (m, 3H), 7.88 (dd, J ) 7.8, 1.2 Hz, 1H); 13C NMR δ
25.6, 32.6, 35.3, 38.3, 57.3, 127.3, 129.5, 130.8, 133.3, 134.2,
145.5, 199.3, 210.5. Anal. Calcd for C15H16O2: C, 78.92; H, 7.06.
Found: C, 79.25; H, 7.20.
1.07 (m, 2H), 1.38-1.43 (m, 4H), 1.90-2.21 (m, 6H), 2.63-
2.70 (m, 2H), 2.95 (t, J ) 9 Hz, 2H), 3.50 (dd, J ) 15, 3 Hz,
2H), 7.10-7.33 (m, 3H), 7.99 (d, J ) 9 Hz, 1H); 13C NMR δ
24.1, 24.5, 28.8, 31.4, 37.8, 44.1, 58.9, 59.0, 127.3, 127.4, 128.8,
129.8, 137.5, 139.5, 205.5. Anal. Calcd for C18H22OS2: C, 67.78;
H, 6.96. Found: C, 67.79; H, 6.96.
Ack n ow led gm en t. This investigation received fi-
nancial support from CSIR, New Delhi [Grant No. 01-
(1504)/98]. U.J . is thankful to CSIR for his fellowship.
We sincerely express our gratitude to Mr. S. P. Rath
and Mr. S. Pattanayak of the department of Inorganic
Chemistry, IACS, for their help in determining the
X-ray structure of 15a .
Su p p or tin g In for m a tion Ava ila ble: Tables of crystal
data, structure solution and refinement, atomic coordinates,
bond lengths and angles, and anisotropic thermal parameters
for 15a . This material is available free of charge via the
Internet at http://pubs.acs.org.
Diketone 27, yield 93%, solid, mp 106 °C; IR (KBr) 1690,
1630, 1590 cm-1; 1H NMR δ 1.47-1.78 (m, 10H), 2.30 (broad,
2H), 2.78 (m, 2H), 3.85 (s, 3H), 6.65 (d, J ) 2.4 Hz, 1H), 6.87
(dd, J ) 9, 1.8 Hz, 1H), 8.12 (d, J ) 9 Hz, 1H); 13C NMR δ
J O990634S