- Email: [email protected]
Studies directed toward the total synthesis of tetronolide 1. An enantioselective synthesis of the octahydronaphthalene unit
Tchahcdron Pr1nkd
Lcrrcrs,
Vol32.
No 33, pp 40914091.
1991
w40-4039/91 Pcrgamon
,I! Great Hrllaln
STUDIES
DIRECTED
TOWARD THE TOTAL SYNTHESIS
AN ENANTIOSELECTIVE
SYNTHESIS
Robert K Boeckman Jr ,+ Thomas
E Barta.
Department
of Chemistry
Unlverslty
of Rochester
Rochester, New York
Summary
An efficfent enanboseieciwe route to the actahydronaphlhabne
couptmg of the two key fragments land The tetrocarcms reLtea‘t0
kljanoiia8
comprise
complex
ofa naturaily-OCCurrIng
of the intramolecular
Diels-Alder
G Nelson
14627
The sequence employs the mtramolecular D/e/s-Aider reaction to
on the trans decalm rmg system, and tncorporates a masked acyfahng agent which should permit 3 as demonstrated by react/on of pentaene
ofantitumor antIbiotIc
ana’ctilbrotlincolia’e,
family 2,3 These structurally SyntheSlS
a group
Scott
UNIT
uaf preseni II) tetronollde (I), the stereochem~calty complex aglycone
common to the telrocarcms, a novel group of anlilumor substances, IS described control the relatrve stereochem/strypresent
and
(
1.
OF TETRONOLIDE
OF THE OCTAHYDRONAPHTHALENE
%3.00+ Press plc
the aglpcone aglycones
member ofthls cycloaddlbon,
4
wth methanol and a mode/ a-hydroxy ester
agents which share a comm0n
umfs of Illanomycin
and’chlbrothncm,
have been the sublect of conslderable Ciass has yet been completed
we chose tetronollde
aglycone,
tetronolide
1 .i
Structurally,
the onl) other known members effort dlrected
toward their preparation,
4 In accord with our Interest In developing
to test the scope of this methodology
ofthrs
We conceived
tetronoltde
IS
natural product although
stereoselective a convergent
no total variants
synthetic
OTBS
OK,
’
TBOPSO
+
“OMOM P(OlWzHdz
6
7
5
4
strategy (Scheme
I), whose Impl’ementatlon
octahydronapthalene
2 and cyclohexene
4, an enantlomencally
pure precursor
The advantages of 2 was recognzed
required’the
3 subunits of
preparation,
1or
precursors
in enantiomerMy thereof
pure ion,
ano’unlon
oftwo key syntnons comprlsmg
Herein, we descnbe the development
the
of a sultable route to pentaene
of X5x6
of employing
a [4+2] cycloaddltlon
to control the relative
early on, and this strategy has been employed
stereochemistry
by several groups 738 However,
4091
of centers our approach
present
on the decaltn framework
differs slgnlficantly
rn the manner
4092
by which the major fragments will be joined, since in all other studies to dale the major subunits are to be joined in a separate step, whereas we envisioned the coupling process in tandem with the intramolecular [412] cycloaddition.
Thus, the required substrate for construction of 2 becomes
pentaene 4, whose synthesis is outlined below. The requisite pentaene 4 was expected to arise via the sequential corn bination of phosphine oxide 5 and dioxinone phosphonate 6 with an appropriate aldehyde derived from enantiomerically
HOJ.?+MHL MPMOwoH
pure, differentially protected trio1 7 (Scheme 1).
MPMO~,,
c,d
MPMOL
A
%eagentS:
a) NaH, @H3OPhGH$l,
THF, 25%.
NCSIDMS, CH$l2% O’C 0.5h; e) PhpPLi, THF, Preparation of 5 was accomplished
-78*C,
step (Eqn 1) from dioxinone 912
-78”-+
25’C,
lh; c) IAH,
THF, O’C, 5h; d)
lh then [email protected], O’C, 5 mm.
by conversion of E-2-methyl-2-pentene-4-yn-l-01
standard methodology (69% overall) as shown in Scheme 2. 9-l exposure of 8 to fithio diphenylphosphine
lomh then (CH20),,
12h; b) nBuLi. -7Q’C, THF.
P(O)Ph,
5
8
to E, E allylic chloride 8 in 4 steps employing
i Chloride 8 was then converted to the required phosphine oxide 5 in 50% yield by
and subsequent oxidation with H&
in CH2Cl2 at O’C. Dioxinone phosphonate 6 was obtained in a single
ua conversion to the lithium enolate with IDA and treatment with diethylchlorophosphite,
followed by oxidation in
situ (H202, CH2Cl2,O”C) to afford a 60% yield of phosphonate 6.13 l)LDA/THF/-76°C then CIP((X;,H,), o&
(1)
-78% + 25% W’W’%Hd,
2) H&‘CH,CI#C
Construction of the enantiomerically in 5 sleps using standard methods to aIdehyde diethylphosphonoacetate
pure trio1 7 was initiated from (R)-(-)-methyl
3.hydroxy-2-methylpropionate
which was converted
in 73% overall yield (Scheme 3). Condensation of aldehyde 10 with the sodium anion of ethyl
afforded the expected E unsaturated ester’11 (97%) which provided allylic alcohol 12 upon reduction with DIBAL-H
(95%). The two remaining stereogenic centers were installed via 3 step sequence involving catalytic asymmetric epoxidationl$ alcohol 13 (88%, 88% de), followed by benzylation,
and treatment of the protected epoxide with lithium dimethylcuprate
to afford epoxy
in Et20 at -45’C to
afford a mixture (7:1) of diastereomeric alcohols 14 and 15 (86% combined from 13). I5 Protection of the remaining alcohol as the methoxymethyl ether then furnished a readily separable mixture of the desired trio1 7 (86%) and its regioisomer 16 (12%).16 Assembly of pentaene 4 from the three major subunits 5-7 was also readily accomplished (Scheme 3). Sequential catalytic debenzylation of 7 (-loo%),
Swem oxidation (90%),t7 and condensation of the resulting aldehyde with the lithium anion derived from 5 at -78’C in THF with
added HMPA smoothly provided, as a single geometric isomer, the E,E,E triene 17 (86%). Repetition of the deprotection, oxidation, olefination sequence on 17 employing instead fluoride to cleave the silyl ether, and the lithium anion derived from 6 in THF with added HMPA delivered exclusively the required Z,E,E,E,E pentaene 4 (53% from 17).‘* With the key pentaene 4 in hand, we were in a position to test whether 4 fulfilled the crucial requirements couplinglcycloaddition
of the intended tandem
assembly of 2 and 3: 1) that the thermally generated acyl ketene undergo efficient intermolecular capture by a suitable 3’
alcohol (ultimately the required cyclohexene synthon 3), and ‘2) that the subsequent cycloaddition proceed with high stereoselectivity correct stereochemica
relationships about the octahydronapthalene
creating the
ring system.lg
To test the essential feasibility of the couplingicycloaddition,
we first examined thermolysis of 4 at
1 IO’?
in the presence of excess
methanol (-100 equiv), which afforded the desired decalin 18 in 54% yield along with 5% of uncharacterized diastereomeric cycloadduct(s)
4093
schwne3a
K&O*CHs abc_
TBDPSOJ__OTs -2% TeDPSOJ+CHO f_ TBDPSOJ/k+Z 10 gG
11 Z=C0,C2HS 12 Z= CH20H
c-p- ““-2.,,, :Bo:Ifl,,oR i lTzL MpMo~,,, HO
7
17
I
OR
15 R-H 16 F&MOM
13
CO&Ho
CH,W
20 aReagents
a)
TBDPSCI, lmldazole (2 equlv)
,25%,5h, b) DIBAL-H
(1 11, A, 10h. e) DIBAL-H, THF, -78’+ 78%
2h, h)[email protected])4
25’C,
(2 equlv), THF, -78’C, 2h.
lh. I) [email protected](O)(CC2H5)2,
(catalflic). (-)DET (catalflic), BuOH,
CH$l2,
-20%
C) TsCI,
DMAP, Py, CH$+,
25’C, 12h, d) KCN, E~oH-H~o
NaH. THF, -78’ + 25’C, lOh, g) DIBAL-H (2 equw), THF, 24h, i) NaH, PhCHpEr, THF, 25’C. 1 h, 1) (CH~)@LI
820, -45’C, 2h, k) CH3GCH2CL EtN(1Pri2, THF. 25’C, 12h, I) H2 (1 atm), PdlC, EtOH, 25’C, lOh, m) (0X1)2,
-
(10 eqw],
DMSO, Et3N, -78’C, lh, n) 5,
~BuLI, THF-HMPA (2 l), -78’C, lh. a) TBAF, THF, 25’lC, 5h, p) 6, n3uL1, THF-HMPA (2 I), -7E°C, 2h, q) A (toluene
110 ‘C (sealed tube), or
xylenes, i30°C (sealed tube)) (Scheme 3) The stereochemrstry of 18 was confirmed wa 300 and 500 MHz NMR spectroscopy with appropnate decoupling 2o This result IS COnSSfenfwith the expectatmn that fhe cyclizatlon
woul’doccur
wourd be Imparted by the C-3 subsntuent wnrcii preferentially bonded InteractIon with the C-8 proton 466~1
nearly excl’uslvel) through an end&chair transttlon state in which the taclal 1318s occupies an equatorral orlenratlon rn the transltion state so as to alleviate a non-
We have also demonstrated the capture of a model 3’ nucleophile in the form of hydroxy ester 19,
which afforded the related decalin 20 (-50%, unoptlmlzed, SO
1 stereoselectivrty) upon thermolysrs of 4 at 13O’C In xylenes m the presence of 1
equlv of 19
t2)
CH,
4094
Our studies have resulted in the development of an enantioselective feasrbility of a tandem couplinglcycloaddition
route to key pentaene synthon 4 and the demonstration
methodolgy for the stereoselective
preparation
following communication details our approach to cyclohexene 3. Application of this methodology
of octahydronaphthalene
subunits for
of the
1. The
to the total synthesis of tetronolide 1 is currently
under investigation.
B.
We are grateful to the National Cancer Institute of the National Institutes of Health for the award of a research grant (CA-
29108) in support of these studies. We thank the Merck Co. for fellowship support awarded to SGN.
References and Notes:
(1) Tamioki, T.; Kasai, M.; Shirahata, K.; Tomita, F. J. Antibiotics. 1982, 35,979. (2) Waitz, J. A.: Horan. A. C.; Kalyanpur, M.; Lee, 8. K.; Loebenberg, D.; Marquer. J. A.; Miller, G.: Patel, M, G. j. Anlibiotics1981.34,
1101.
(3) Keller-Schierlein, W.; Muntwyler, R.; Pache, W.; Zahnet, H. He/v. Ctim. Acfa. 1969, 52, 127. (4) For leading references to prior workon chlorothrlcolide and kljanolide see: (a) Marshall, J. A.; Salovich, J. M.; Shearer, B. G. J. Org. Cbem. 1990,55,2398.
(b)Takeda, K.; Igharashl, Y.; Okazaki, K.; ‘foshii, E.; Yamaguchi, K. J’. Org. Chem. 1990,55,3431.
(c) Roush. W. R.: Kageyama,
M.; Riva, R.: Brown, B. B.; Warmus, J. S.; Moriarity, K. J. d Org. Cbem. 1991, 56, 1192. (5) Taken in part from the Ph. D. dissertation of Thomas E. Barta, University of Rochester, 1987. (6) Boeckman, Jr., R. K.; Bana, T. E. J. Org. Chem. 1985,50,3421. (7) Okumura. K.; Okazaki, K.; Takeda, K.; Yoshii, E. Tefrahedron Leff. 1989,30, 2233. (8) Ireiand, R. t.; Vamey, M. D. J. 0~. Chem 1986, 57,635. (9) Corey, E. J.; Katzenellenbogen, N.; Gilman, N. W.; Roman, A.; Erickson, 8. W. J. Am. Chem. Sot. 1968, 9Q,5618. (10) Corey, E. J.; Kim, C. U.; Takeda, M. Tetrahedron iefl. 1972, 4339. (11) All new substances exhibited satisfactory spectral (NMR, IR, MS) data and microanalytical or high resolution MS data. (12) Sato, M.; Ogasawara, H.:Oi, K.; Kato, T. &em. Pbarm. &ii.
1983, 31, 1896.
(13) Boeckman, Jr., R. K.; Kamenecka, T. M.: Nelson, S. G ; Pruift, J. P.; Baffa, T. E. TeBahedron Left, 1991,32, 0000. (14) Hanson, R. M.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922. (15) Johnson, M. R.; Kishi, Y. Tetrahedron Lett. 1979, 4347. (16) The minor isomers incurred in the asymmetric epoxidation and the subsequent epoxide opening were removed at the protected trio1 stage by chromatography(flash
or prep HPLC] to give 7 as a homogeneous substance.
(17) Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem. 1978,43, 2480. (18) The dioxinone phosphonate Olefination proceeded in unsatisfactory yields in the absence of HMPA. Yields improved dramatically when a solution of the aldehyde in THF:HMPA(l :l, 1 M overall) was added to the lithiated phosphonate. (t9) Boeckman, Jr., R. K.;Pruitl,J. Ft. J. Am. Chem. Sot. 1989, 117,8286. (20)
DeCOUpling
experiments verified that the C2-C7 coupling constant for the ring junction protons, and the C&7
coupling constant for the CI-
OMOM and adjacent ring junction protons were J=fO.3 Hz and J=8.1 Hz respectively, consistent with frans-diaxial relationships between these protons and thus with ffans- fused decalin 18 (Eqn 2). (21) Marshall, J. A.; Grote, J.; Audia, J. E. J. Am, Chem. Sot.. 1987, 109, 1186.
(Received in USA 26 April 1991)
Lcrrcrs,
Vol32.
No 33, pp 40914091.
1991
w40-4039/91 Pcrgamon
,I! Great Hrllaln
STUDIES
DIRECTED
TOWARD THE TOTAL SYNTHESIS
AN ENANTIOSELECTIVE
SYNTHESIS
Robert K Boeckman Jr ,+ Thomas
E Barta.
Department
of Chemistry
Unlverslty
of Rochester
Rochester, New York
Summary
An efficfent enanboseieciwe route to the actahydronaphlhabne
couptmg of the two key fragments land The tetrocarcms reLtea‘t0
kljanoiia8
comprise
complex
ofa naturaily-OCCurrIng
of the intramolecular
Diels-Alder
G Nelson
14627
The sequence employs the mtramolecular D/e/s-Aider reaction to
on the trans decalm rmg system, and tncorporates a masked acyfahng agent which should permit 3 as demonstrated by react/on of pentaene
ofantitumor antIbiotIc
ana’ctilbrotlincolia’e,
family 2,3 These structurally SyntheSlS
a group
Scott
UNIT
uaf preseni II) tetronollde (I), the stereochem~calty complex aglycone
common to the telrocarcms, a novel group of anlilumor substances, IS described control the relatrve stereochem/strypresent
and
(
1.
OF TETRONOLIDE
OF THE OCTAHYDRONAPHTHALENE
%3.00+ Press plc
the aglpcone aglycones
member ofthls cycloaddlbon,
4
wth methanol and a mode/ a-hydroxy ester
agents which share a comm0n
umfs of Illanomycin
and’chlbrothncm,
have been the sublect of conslderable Ciass has yet been completed
we chose tetronollde
aglycone,
tetronolide
1 .i
Structurally,
the onl) other known members effort dlrected
toward their preparation,
4 In accord with our Interest In developing
to test the scope of this methodology
ofthrs
We conceived
tetronoltde
IS
natural product although
stereoselective a convergent
no total variants
synthetic
OTBS
OK,
’
TBOPSO
+
“OMOM P(OlWzHdz
6
7
5
4
strategy (Scheme
I), whose Impl’ementatlon
octahydronapthalene
2 and cyclohexene
4, an enantlomencally
pure precursor
The advantages of 2 was recognzed
required’the
3 subunits of
preparation,
1or
precursors
in enantiomerMy thereof
pure ion,
ano’unlon
oftwo key syntnons comprlsmg
Herein, we descnbe the development
the
of a sultable route to pentaene
of X5x6
of employing
a [4+2] cycloaddltlon
to control the relative
early on, and this strategy has been employed
stereochemistry
by several groups 738 However,
4091
of centers our approach
present
on the decaltn framework
differs slgnlficantly
rn the manner
4092
by which the major fragments will be joined, since in all other studies to dale the major subunits are to be joined in a separate step, whereas we envisioned the coupling process in tandem with the intramolecular [412] cycloaddition.
Thus, the required substrate for construction of 2 becomes
pentaene 4, whose synthesis is outlined below. The requisite pentaene 4 was expected to arise via the sequential corn bination of phosphine oxide 5 and dioxinone phosphonate 6 with an appropriate aldehyde derived from enantiomerically
HOJ.?+MHL MPMOwoH
pure, differentially protected trio1 7 (Scheme 1).
MPMO~,,
c,d
MPMOL
A
%eagentS:
a) NaH, @H3OPhGH$l,
THF, 25%.
NCSIDMS, CH$l2% O’C 0.5h; e) PhpPLi, THF, Preparation of 5 was accomplished
-78*C,
step (Eqn 1) from dioxinone 912
-78”-+
25’C,
lh; c) IAH,
THF, O’C, 5h; d)
lh then [email protected], O’C, 5 mm.
by conversion of E-2-methyl-2-pentene-4-yn-l-01
standard methodology (69% overall) as shown in Scheme 2. 9-l exposure of 8 to fithio diphenylphosphine
lomh then (CH20),,
12h; b) nBuLi. -7Q’C, THF.
P(O)Ph,
5
8
to E, E allylic chloride 8 in 4 steps employing
i Chloride 8 was then converted to the required phosphine oxide 5 in 50% yield by
and subsequent oxidation with H&
in CH2Cl2 at O’C. Dioxinone phosphonate 6 was obtained in a single
ua conversion to the lithium enolate with IDA and treatment with diethylchlorophosphite,
followed by oxidation in
situ (H202, CH2Cl2,O”C) to afford a 60% yield of phosphonate 6.13 l)LDA/THF/-76°C then CIP((X;,H,), o&
(1)
-78% + 25% W’W’%Hd,
2) H&‘CH,CI#C
Construction of the enantiomerically in 5 sleps using standard methods to aIdehyde diethylphosphonoacetate
pure trio1 7 was initiated from (R)-(-)-methyl
3.hydroxy-2-methylpropionate
which was converted
in 73% overall yield (Scheme 3). Condensation of aldehyde 10 with the sodium anion of ethyl
afforded the expected E unsaturated ester’11 (97%) which provided allylic alcohol 12 upon reduction with DIBAL-H
(95%). The two remaining stereogenic centers were installed via 3 step sequence involving catalytic asymmetric epoxidationl$ alcohol 13 (88%, 88% de), followed by benzylation,
and treatment of the protected epoxide with lithium dimethylcuprate
to afford epoxy
in Et20 at -45’C to
afford a mixture (7:1) of diastereomeric alcohols 14 and 15 (86% combined from 13). I5 Protection of the remaining alcohol as the methoxymethyl ether then furnished a readily separable mixture of the desired trio1 7 (86%) and its regioisomer 16 (12%).16 Assembly of pentaene 4 from the three major subunits 5-7 was also readily accomplished (Scheme 3). Sequential catalytic debenzylation of 7 (-loo%),
Swem oxidation (90%),t7 and condensation of the resulting aldehyde with the lithium anion derived from 5 at -78’C in THF with
added HMPA smoothly provided, as a single geometric isomer, the E,E,E triene 17 (86%). Repetition of the deprotection, oxidation, olefination sequence on 17 employing instead fluoride to cleave the silyl ether, and the lithium anion derived from 6 in THF with added HMPA delivered exclusively the required Z,E,E,E,E pentaene 4 (53% from 17).‘* With the key pentaene 4 in hand, we were in a position to test whether 4 fulfilled the crucial requirements couplinglcycloaddition
of the intended tandem
assembly of 2 and 3: 1) that the thermally generated acyl ketene undergo efficient intermolecular capture by a suitable 3’
alcohol (ultimately the required cyclohexene synthon 3), and ‘2) that the subsequent cycloaddition proceed with high stereoselectivity correct stereochemica
relationships about the octahydronapthalene
creating the
ring system.lg
To test the essential feasibility of the couplingicycloaddition,
we first examined thermolysis of 4 at
1 IO’?
in the presence of excess
methanol (-100 equiv), which afforded the desired decalin 18 in 54% yield along with 5% of uncharacterized diastereomeric cycloadduct(s)
4093
schwne3a
K&O*CHs abc_
TBDPSOJ__OTs -2% TeDPSOJ+CHO f_ TBDPSOJ/k+Z 10 gG
11 Z=C0,C2HS 12 Z= CH20H
c-p- ““-2.,,, :Bo:Ifl,,oR i lTzL MpMo~,,, HO
7
17
I
OR
15 R-H 16 F&MOM
13
CO&Ho
CH,W
20 aReagents
a)
TBDPSCI, lmldazole (2 equlv)
,25%,5h, b) DIBAL-H
(1 11, A, 10h. e) DIBAL-H, THF, -78’+ 78%
2h, h)[email protected])4
25’C,
(2 equlv), THF, -78’C, 2h.
lh. I) [email protected](O)(CC2H5)2,
(catalflic). (-)DET (catalflic), BuOH,
CH$l2,
-20%
C) TsCI,
DMAP, Py, CH$+,
25’C, 12h, d) KCN, E~oH-H~o
NaH. THF, -78’ + 25’C, lOh, g) DIBAL-H (2 equw), THF, 24h, i) NaH, PhCHpEr, THF, 25’C. 1 h, 1) (CH~)@LI
820, -45’C, 2h, k) CH3GCH2CL EtN(1Pri2, THF. 25’C, 12h, I) H2 (1 atm), PdlC, EtOH, 25’C, lOh, m) (0X1)2,
-
(10 eqw],
DMSO, Et3N, -78’C, lh, n) 5,
~BuLI, THF-HMPA (2 l), -78’C, lh. a) TBAF, THF, 25’lC, 5h, p) 6, n3uL1, THF-HMPA (2 I), -7E°C, 2h, q) A (toluene
110 ‘C (sealed tube), or
xylenes, i30°C (sealed tube)) (Scheme 3) The stereochemrstry of 18 was confirmed wa 300 and 500 MHz NMR spectroscopy with appropnate decoupling 2o This result IS COnSSfenfwith the expectatmn that fhe cyclizatlon
woul’doccur
wourd be Imparted by the C-3 subsntuent wnrcii preferentially bonded InteractIon with the C-8 proton 466~1
nearly excl’uslvel) through an end&chair transttlon state in which the taclal 1318s occupies an equatorral orlenratlon rn the transltion state so as to alleviate a non-
We have also demonstrated the capture of a model 3’ nucleophile in the form of hydroxy ester 19,
which afforded the related decalin 20 (-50%, unoptlmlzed, SO
1 stereoselectivrty) upon thermolysrs of 4 at 13O’C In xylenes m the presence of 1
equlv of 19
t2)
CH,
4094
Our studies have resulted in the development of an enantioselective feasrbility of a tandem couplinglcycloaddition
route to key pentaene synthon 4 and the demonstration
methodolgy for the stereoselective
preparation
following communication details our approach to cyclohexene 3. Application of this methodology
of octahydronaphthalene
subunits for
of the
1. The
to the total synthesis of tetronolide 1 is currently
under investigation.
B.
We are grateful to the National Cancer Institute of the National Institutes of Health for the award of a research grant (CA-
29108) in support of these studies. We thank the Merck Co. for fellowship support awarded to SGN.
References and Notes:
(1) Tamioki, T.; Kasai, M.; Shirahata, K.; Tomita, F. J. Antibiotics. 1982, 35,979. (2) Waitz, J. A.: Horan. A. C.; Kalyanpur, M.; Lee, 8. K.; Loebenberg, D.; Marquer. J. A.; Miller, G.: Patel, M, G. j. Anlibiotics1981.34,
1101.
(3) Keller-Schierlein, W.; Muntwyler, R.; Pache, W.; Zahnet, H. He/v. Ctim. Acfa. 1969, 52, 127. (4) For leading references to prior workon chlorothrlcolide and kljanolide see: (a) Marshall, J. A.; Salovich, J. M.; Shearer, B. G. J. Org. Cbem. 1990,55,2398.
(b)Takeda, K.; Igharashl, Y.; Okazaki, K.; ‘foshii, E.; Yamaguchi, K. J’. Org. Chem. 1990,55,3431.
(c) Roush. W. R.: Kageyama,
M.; Riva, R.: Brown, B. B.; Warmus, J. S.; Moriarity, K. J. d Org. Cbem. 1991, 56, 1192. (5) Taken in part from the Ph. D. dissertation of Thomas E. Barta, University of Rochester, 1987. (6) Boeckman, Jr., R. K.; Bana, T. E. J. Org. Chem. 1985,50,3421. (7) Okumura. K.; Okazaki, K.; Takeda, K.; Yoshii, E. Tefrahedron Leff. 1989,30, 2233. (8) Ireiand, R. t.; Vamey, M. D. J. 0~. Chem 1986, 57,635. (9) Corey, E. J.; Katzenellenbogen, N.; Gilman, N. W.; Roman, A.; Erickson, 8. W. J. Am. Chem. Sot. 1968, 9Q,5618. (10) Corey, E. J.; Kim, C. U.; Takeda, M. Tetrahedron iefl. 1972, 4339. (11) All new substances exhibited satisfactory spectral (NMR, IR, MS) data and microanalytical or high resolution MS data. (12) Sato, M.; Ogasawara, H.:Oi, K.; Kato, T. &em. Pbarm. &ii.
1983, 31, 1896.
(13) Boeckman, Jr., R. K.; Kamenecka, T. M.: Nelson, S. G ; Pruift, J. P.; Baffa, T. E. TeBahedron Left, 1991,32, 0000. (14) Hanson, R. M.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922. (15) Johnson, M. R.; Kishi, Y. Tetrahedron Lett. 1979, 4347. (16) The minor isomers incurred in the asymmetric epoxidation and the subsequent epoxide opening were removed at the protected trio1 stage by chromatography(flash
or prep HPLC] to give 7 as a homogeneous substance.
(17) Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem. 1978,43, 2480. (18) The dioxinone phosphonate Olefination proceeded in unsatisfactory yields in the absence of HMPA. Yields improved dramatically when a solution of the aldehyde in THF:HMPA(l :l, 1 M overall) was added to the lithiated phosphonate. (t9) Boeckman, Jr., R. K.;Pruitl,J. Ft. J. Am. Chem. Sot. 1989, 117,8286. (20)
DeCOUpling
experiments verified that the C2-C7 coupling constant for the ring junction protons, and the C&7
coupling constant for the CI-
OMOM and adjacent ring junction protons were J=fO.3 Hz and J=8.1 Hz respectively, consistent with frans-diaxial relationships between these protons and thus with ffans- fused decalin 18 (Eqn 2). (21) Marshall, J. A.; Grote, J.; Audia, J. E. J. Am, Chem. Sot.. 1987, 109, 1186.
(Received in USA 26 April 1991)