- Email: [email protected]
Catalytic asymmetric nitroaldol reaction: An efficient synthesis of (S) propranolol using the lanthanum binaphthol complex
Tet&edmn
0040-4039,93 36.00 + .OO PU8unOn h‘S Ltd
Letters. VoL 34. No. 5. pp. 85858.1993
FrimdinGnatB~
Catalytic Asymmetric Nitroaldol Reaction: An Efficient Synthesis of (s) Propranolol Using the Lanthanum Binaphthol Complex
Nitmaldol maction (Henry xeactioa~ is one d the power&Y synth&
methods in organic syntksis.
because oitl0aldols are easily tmnsfarmed into vatioususefulderivativessuchu&aminoakoholrandahydroxycarbonylcompounds. fMminoalcoholsrrefoundubqnxtantpartial sauumesofmanybioaaive compound8 such as a@-adrena@ agonists or antagonist&3 HIV pmtease inhibiton and an&mgal or autibactaMpepddes.~ Inrpiotofthis~~~nitroalQlructioruhavenotkensowell~~unoil reantly cqcially
ia asymmetric control. We have abeady qorted
that the optically active lanthanum
akoxide is a versatile catalyst for C-C bond-fcxming rc(Lctiolu which involve an asymmetric niaolldd reaction.~ In this paper, as an effective utikatioa
of our Ian&mum binaphthol complex. a convenient
preparation of optically active (S) propmnolol, which is a representative of bioactive B-amino alcohol compotmd&isptesented. As orher B_blockers, the optically active (S) propranolol shows cardiovascular diseases than both its (R) form and racemate. l’kefoq
Stronger
fl-blocking efficacy in
many methods of (.V)propranolol
prquation have been published.7 However, thue has been no sport in which a niax&iol twction is used as a key step. We planned to apply a catalytic asymmetric nitroaldol reaction using the lanthanum-(R)-(+)binaphthol complex to a new synthetic approach to (A’)pmpranolol. The requisite aldehyde 1 wasfirst ptepamd from a-naphthol in two steps.8 After several attempts. we wete pleased to find that treatment of 1 with nitromethane at -50 “C in the presence of the asymmetric catalyst (10 moi %), which was pnpared iknn LaCl3-7Hfl. dilithium (R)-(+)-binaphthoxide(1 mol cquiv), NaO-r-Bu( 1 mol equiv) and Hfl4
mol equiv) in TI@ gave the nitma&
(Scheme 1). Even at -25 % using this lanthanum-@)-(+>biiphthol
2 of 92% eel0 io 80% yield
complex, the niaoaldol2 was obtained
maintaining the high enantiomeric selectivity (87% ee).
Scheme 1 855
88%(92% 88)
856
WiththenitroalQl2d92%~avrikble,tbeMgeWaS~tfOrFeductionofthenitrogrouptothe correspondingprimary amino functionality folloWed by alkylation with retention of the absolute
. contiguntlan . Thedcdledamvcrsioo
wasbcstcaniaioutbycatalytkhydrogcnationovcrI’Qfdlowcdby
drlitiwdrcetareIrrbowniaSc~5ploducing(SH-)_~of92%ain9096yield.
ltm5.a
catalyticuymmeeic syntbesiaof (A’)-(-)-pqranoId (92% ec) baabeen achievedin a t~wtcp scqucnccof
. teaaKmsst8rtingwith1(72%ovwallyicld).
F-,reayrtallicationoftheHclsaltofpropnadal
(929bae)fnmAcoEt-M6oH~touadtogivedreopticallypraedrug.
10% Pm& Ha MeOIi,rt,2hr thenSOY!,16hr
Scheme2
Table 1. Reactianof the Aldehyde 1 with Nitromthane may
cataly!sta
=lve!lt -PC0
lb La-(R)-BINOL THF 2C La-(R)-BINOL THP 3&e 3 tolutulcd 4&e 4 toluell&t sb*= g toluened
-25 -50 -20 -20
-m
vllearrlylt(lOmol%)wnnmalia~“c!H#@(lomd qdv)mrawd. ‘cH*(sod eqtdv)wmuld
time@)
yieW%) d’k)
17 60 19 72
62 80 41 60
72
36
~TOtWWWrrpand~bOtllEmoltmiubhlDlVQL
lW(1Jmdoquiv~dle-
dt)V~USd.
87 0 920 230 160
3(R)
858
RefaunusandNotee 1.
ODhVCfNXUUpjoha-
2.
a) Sdmch,
D.; Chin,
.
Limited, Tsukuba, Japan.
E. W.; Lehr, F.; Wekr, T., Chhdu, 1979.33.1.
b) Rosini, 0.; BalIhi, R, Synthesis, 1988,833. 3.
RccentIymmepotcnt&-adtwqka8onisuwue&vcI~
sac:
a) Bloom, J. D.; Dutia, M. D.; Johnson, B. D.; Wirsacr, k, Burns, M. 0.; Lacgis, E. E, Dolan, J. A.; CIaus, T. I-L,J. Med. Gem., 1992.35.3081. b) Howe, R; Rae, B. S.; HoIIoway, B. R.; Stribling, D., J. hfed. Chn., 1992,35.1751. 4.
Askin. D.; Wake,
M. A.; Vacca, J. P.; Rcamex, R. A.; VoIantc, R P.; Shinkai, I., J. Org. Chem.. 1992.
57.2771. 5.
Ohfmw, Y.. Act. Chem. R-es., 1992925,360.
6.
Sasaj R; Suzuki, T.; Arai. S.; hi.
7.
noncqmaticasymmctricsyntIxsihsee: Far=-tIynpmedpreperatmof(Qpropnndolby a) Bedhat& H. S.; Banaji, A. A., J. Org. Chtm., 1991.56.5372. b) Takahhi,
T.; Shibaaaki. M., 1. Am. Chem. Sot., 1992,114,4418.
K; Sakumba, S.; Takcda, R; Achiwa, K, /. Am. Ch.
Sot., 19!)0,112,5876.
c) Khmder, J. M.; Ko, S. Y.; Shmpless. K. B., J. Org. Chem., 19&&51.3710 and rdsnccs
cited
tkcin. 8. 9. 10. 11.
Dumriy kL; vo-Quang, Y.; vo-Quang. L; eoffic, I? L., synthesis, 1989.64. Sasai, K, Suzuki, T.; Itoh, N.; Shibasaki, M., Tetruhedron L&Z., the pnxeding paper in this issue. The optical purity was determined by HPLC analysis (DAICEL CHIRALPAK AS or AD). a) @donna, S.; Re. A.; Wynbcrg, H.. J. Chem. Sot. Perkin Tmns. 1,19gl, 547. b) Corm. R S. H; Lovdi, A. V.; Kady. S.; Weinstak
L M., 1. Org. Ckm., lw16.51.4710.
c) Scra, A.; Takagi. K.; Katayama, H.; Yamada, )t, Matsumoto. K., J. Org. Ckm., 1988.53.1157. 12.
Inthecasednitrotthane,boththedias~~andenantiomericexcesses~imprwedat-40oC: syn (82% cc)/anti (52% cc) = 2.7:1
13. TheabrdPte~~onofthecarbonsdjacenttothehydroxylgroupwasdeterminedtobeS
(HIXC)
by compntison with opticxliy active 8a derived from 2 in three steps (silylation, methylxtion xnd deprw&n).
The absolute configuration of the xsymmeUic center adjacent to the nit10 group xnd the
~~coafiguratioasof&and8bwereelucidatedbydrecouplingcoas~~oftheviciaal~~and the NOE experiments as shown below.
(Received in Japan 25 September 1992)
0040-4039,93 36.00 + .OO PU8unOn h‘S Ltd
Letters. VoL 34. No. 5. pp. 85858.1993
FrimdinGnatB~
Catalytic Asymmetric Nitroaldol Reaction: An Efficient Synthesis of (s) Propranolol Using the Lanthanum Binaphthol Complex
Nitmaldol maction (Henry xeactioa~ is one d the power&Y synth&
methods in organic syntksis.
because oitl0aldols are easily tmnsfarmed into vatioususefulderivativessuchu&aminoakoholrandahydroxycarbonylcompounds. fMminoalcoholsrrefoundubqnxtantpartial sauumesofmanybioaaive compound8 such as a@-adrena@ agonists or antagonist&3 HIV pmtease inhibiton and an&mgal or autibactaMpepddes.~ Inrpiotofthis~~~nitroalQlructioruhavenotkensowell~~unoil reantly cqcially
ia asymmetric control. We have abeady qorted
that the optically active lanthanum
akoxide is a versatile catalyst for C-C bond-fcxming rc(Lctiolu which involve an asymmetric niaolldd reaction.~ In this paper, as an effective utikatioa
of our Ian&mum binaphthol complex. a convenient
preparation of optically active (S) propmnolol, which is a representative of bioactive B-amino alcohol compotmd&isptesented. As orher B_blockers, the optically active (S) propranolol shows cardiovascular diseases than both its (R) form and racemate. l’kefoq
Stronger
fl-blocking efficacy in
many methods of (.V)propranolol
prquation have been published.7 However, thue has been no sport in which a niax&iol twction is used as a key step. We planned to apply a catalytic asymmetric nitroaldol reaction using the lanthanum-(R)-(+)binaphthol complex to a new synthetic approach to (A’)pmpranolol. The requisite aldehyde 1 wasfirst ptepamd from a-naphthol in two steps.8 After several attempts. we wete pleased to find that treatment of 1 with nitromethane at -50 “C in the presence of the asymmetric catalyst (10 moi %), which was pnpared iknn LaCl3-7Hfl. dilithium (R)-(+)-binaphthoxide(1 mol cquiv), NaO-r-Bu( 1 mol equiv) and Hfl4
mol equiv) in TI@ gave the nitma&
(Scheme 1). Even at -25 % using this lanthanum-@)-(+>biiphthol
2 of 92% eel0 io 80% yield
complex, the niaoaldol2 was obtained
maintaining the high enantiomeric selectivity (87% ee).
Scheme 1 855
88%(92% 88)
856
WiththenitroalQl2d92%~avrikble,tbeMgeWaS~tfOrFeductionofthenitrogrouptothe correspondingprimary amino functionality folloWed by alkylation with retention of the absolute
. contiguntlan . Thedcdledamvcrsioo
wasbcstcaniaioutbycatalytkhydrogcnationovcrI’Qfdlowcdby
drlitiwdrcetareIrrbowniaSc~5ploducing(SH-)_~of92%ain9096yield.
ltm5.a
catalyticuymmeeic syntbesiaof (A’)-(-)-pqranoId (92% ec) baabeen achievedin a t~wtcp scqucnccof
. teaaKmsst8rtingwith1(72%ovwallyicld).
F-,reayrtallicationoftheHclsaltofpropnadal
(929bae)fnmAcoEt-M6oH~touadtogivedreopticallypraedrug.
10% Pm& Ha MeOIi,rt,2hr thenSOY!,16hr
Scheme2
Table 1. Reactianof the Aldehyde 1 with Nitromthane may
cataly!sta
=lve!lt -PC0
lb La-(R)-BINOL THF 2C La-(R)-BINOL THP 3&e 3 tolutulcd 4&e 4 toluell&t sb*= g toluened
-25 -50 -20 -20
-m
vllearrlylt(lOmol%)wnnmalia~“c!H#@(lomd qdv)mrawd. ‘cH*(sod eqtdv)wmuld
time@)
yieW%) d’k)
17 60 19 72
62 80 41 60
72
36
~TOtWWWrrpand~bOtllEmoltmiubhlDlVQL
lW(1Jmdoquiv~dle-
dt)V~USd.
87 0 920 230 160
3(R)
858
RefaunusandNotee 1.
ODhVCfNXUUpjoha-
2.
a) Sdmch,
D.; Chin,
.
Limited, Tsukuba, Japan.
E. W.; Lehr, F.; Wekr, T., Chhdu, 1979.33.1.
b) Rosini, 0.; BalIhi, R, Synthesis, 1988,833. 3.
RccentIymmepotcnt&-adtwqka8onisuwue&vcI~
sac:
a) Bloom, J. D.; Dutia, M. D.; Johnson, B. D.; Wirsacr, k, Burns, M. 0.; Lacgis, E. E, Dolan, J. A.; CIaus, T. I-L,J. Med. Gem., 1992.35.3081. b) Howe, R; Rae, B. S.; HoIIoway, B. R.; Stribling, D., J. hfed. Chn., 1992,35.1751. 4.
Askin. D.; Wake,
M. A.; Vacca, J. P.; Rcamex, R. A.; VoIantc, R P.; Shinkai, I., J. Org. Chem.. 1992.
57.2771. 5.
Ohfmw, Y.. Act. Chem. R-es., 1992925,360.
6.
Sasaj R; Suzuki, T.; Arai. S.; hi.
7.
noncqmaticasymmctricsyntIxsihsee: Far=-tIynpmedpreperatmof(Qpropnndolby a) Bedhat& H. S.; Banaji, A. A., J. Org. Chtm., 1991.56.5372. b) Takahhi,
T.; Shibaaaki. M., 1. Am. Chem. Sot., 1992,114,4418.
K; Sakumba, S.; Takcda, R; Achiwa, K, /. Am. Ch.
Sot., 19!)0,112,5876.
c) Khmder, J. M.; Ko, S. Y.; Shmpless. K. B., J. Org. Chem., 19&&51.3710 and rdsnccs
cited
tkcin. 8. 9. 10. 11.
Dumriy kL; vo-Quang, Y.; vo-Quang. L; eoffic, I? L., synthesis, 1989.64. Sasai, K, Suzuki, T.; Itoh, N.; Shibasaki, M., Tetruhedron L&Z., the pnxeding paper in this issue. The optical purity was determined by HPLC analysis (DAICEL CHIRALPAK AS or AD). a) @donna, S.; Re. A.; Wynbcrg, H.. J. Chem. Sot. Perkin Tmns. 1,19gl, 547. b) Corm. R S. H; Lovdi, A. V.; Kady. S.; Weinstak
L M., 1. Org. Ckm., lw16.51.4710.
c) Scra, A.; Takagi. K.; Katayama, H.; Yamada, )t, Matsumoto. K., J. Org. Ckm., 1988.53.1157. 12.
Inthecasednitrotthane,boththedias~~andenantiomericexcesses~imprwedat-40oC: syn (82% cc)/anti (52% cc) = 2.7:1
13. TheabrdPte~~onofthecarbonsdjacenttothehydroxylgroupwasdeterminedtobeS
(HIXC)
by compntison with opticxliy active 8a derived from 2 in three steps (silylation, methylxtion xnd deprw&n).
The absolute configuration of the xsymmeUic center adjacent to the nit10 group xnd the
~~coafiguratioasof&and8bwereelucidatedbydrecouplingcoas~~oftheviciaal~~and the NOE experiments as shown below.
(Received in Japan 25 September 1992)