Jonathan LocknerBaran Group Meeting Bismuth in Organic Synthesis
Bismuth Factoids...
• mentioned as early as the 1450s as Wismutton or Bisemutum (old German for "white substance")
• employed in metallurgical purposes during 15th and 16th centuries (for instance, bismuth bronze was apparently used by Inca smiths)
"The decorative bronze handle of a tumi excavated at the Inca city of Machu Picchu, Peru, contains 18 percent bismuth and appears to be the first known example of the use of bismuth with tin to make bronze... The use of bismuth facilitates the duplex casting process by which the tumi was made and forms an alloy of unusual color." Science 1984 585
• specifically identified as a metallic element by 1753 (French chemist Claude François Geoffroy)
• heaviest "stable" element in periodic table, with only one "stable" isotope: 209Bi
It has long been suspected (on theoretical grounds) that 209Bi is radioactive, but it was not until 2003 that experiment proved this to be true. French physicists detected α-decay of 209Bi using the scintillating bolometer technique. Indeed, the α-decay of this element is very rare (half-life = 2 x 1019 years!) Nature 2003 876
• touted as an eco-friendly heavy metal (non-toxic and non-carcinogenic) (for instance, showcased at a 2006 IUPAC conference on green chemistry)
• relatively rare: 64th in abundance, comparable to Ag and Cd
• soft, heavy, lustrous, silver-white metal with an iridescent tinge
• serves as a suitable replacement for lead in fireworks, bullets, etc.
"Dragon's eggs are pyrotechnic stars which first burn for a period giving a visual effect then explode with a loud crackling report. Manufacture of this effect has become controversial due to the heavy metals involved in the process, particularly lead tetraoxide (Pb3O4). Nowadays, bismuth trioxide is commonly used as a more environmentally-friendly substitute for lead compounds in achieving the effect, and its occurence in fireworks displays has since become much more common." Wikipedia entry
• one of only two metals that expand on solidification, making its alloys suitable to manufacture of detailed metal castings
• PeptoBismol & Kaopectate, as well as cosmetics...
Ph3Sn Br BiI3−ZnR Rreplaced by:
Jonathan LocknerBaran Group Meeting Bismuth in Organic Synthesis
83rd element, the heaviest pnictogen (group 15)
ground state configuration: [Xe]4f145d106s26p3 (five valence electrons)
most common oxidation states: +3, +5
in water, forms insoluble basic salts
high nucleofugality -- like lead(IV) and iodine(III)
Ph3Bi is better leaving group than OTf, owing to facile BiV/BiIII redox
highly oxidizing, high Lewis acidity, especially for BiV centers
1934 ! Challenger (BiV)
1949 ! Rigby (NaBiO3, Bi2O3)
1960s ! industrial catalysts (Bi-Mo...)
late 1970s to 1980s ! Barton; Dodonov: oxidation & arylation with BiV
mid 1980s ! Wada; Dubac: Barbier-type allylation & aldol with BiIII
late 1980s ! bismuthonium salts and ylides...
1990s ! catalytic oxygenation, Friedel"Crafts acylation, etc.
monographs: Organobismuth Chemistry, Suzuki & Matano, Elsevier 2001
chapter: Main Group Metals in Organic Synthesis, Vol 2, Ch 14, Wiley 2001
R'RCHOH R'RC=O
CHO + CN
BiX3(moisture-sensitive,corrosive)
Bi metal ($0.28/gm)
BiR3 (air & light sensitive)BiX5
BiAr3 (stable crystalline solids)
Ar3BiX2
Ar3RBiX(bismuthonium salts)
Ar3Bi=R(bismuthonium ylides)
(stability depends on substituents)
Ph3Bi $1.90/gm
Ph3BiCl2 $12.60/gm
BiBiCl3BiBr3Bi(OTf)3Bi2O3Bi(OAc)3Bi(NO3)•5H2OBi2(SO4)3NaBiO3Zn(BiO3)2
Bu3BiPh3BiPh3BiCl2Ph3Bi(OAc)2Ph3BiCO3Ph4BiOCOCF3
7440-69-97787-60-2CAS #88189-03-11304-76-322306-37-210035-06-0CAS #12232-99-4CAS #
3692-81-7603-33-8594-30-97239-60-347252-14-283566-43-2
C, X, O, RC, X, R, M
OC, X, R, M
OX, O
C, X, O, MO
O, MO
C, XC, X, OC, X, OC, X, OC, X, OC, X, O
general reviews: Mohan, Tetrahedron 2002 8373; Suzuki, Synthesis 1997 249
C carbon-carbonX carbon-heteroatomO oxidationR reductionM miscellaneous
Ar3BiCl2
NK
O
(2 equiv)
NO
Bi
O
ArAr
ArPyr
N O
Ar
Chem. Lett. 2005 11 1496An Ullman-type coupling that doesn't involve copper, and even works with Ar = o-Tol For any sort of addition or rearrangement, consider using catalytic BiCl3 or Bi(OTf)3
$1.40
$8.00
Jonathan LocknerBaran Group Meeting Bismuth in Organic Synthesis
Oxidative cleavage of 1,2-diols (Barton, Tetrahedron 1986 5627)
Oxidative cleavage of !-ketols (J. Org. Chem. 1993 2196)
Alcohol oxidation (ACIE 2002 3028)
Oxidation of acyloins to !-diketones (Rigby, J. Chem. Soc. 1951 793)
Various oxidations using zinc bismuthate (Bull. Chem. Soc. Jpn. 1992 1131)
Catalytic oxidation of hydrocarbons: propylene (Adv. Catal. 1994 233)
O
OH
NaBiO3
AcOH"H2ORT, 12 h
H
O
OH
O
72%
OH
(o-Tol)3BiCl2"DBU
PhMe, RT, 30 min
CHO
94%
Ph3Bi (0.1 equiv)NBS, K2CO3
CH3CN, RT, 3 h(1% H2O)
72%
cf. Pb(OAc)4, NaIO4, MnO2
R
OH
R
OBi2O3
~100 °C, 15"30 minAcOH"EtOCH2CH2OH
R
O
R
O
(60"95%)
R1R2CHOH
RSH
R1SR2
R1R2C=NOH
Zn(BiO3)2
PhMe, reflux
R1R2C=O (60"100%)
(RS)2 (86"99%)
R1SOR2 (65"78%)
R1R2C=O (0"85%)
cf. BaMnO4, PCC
"superior to conventional oxidizing agents"presumed active species: Bi(OAc)3
O2
Bi"Mo"metal(s)"O
NH3
CHO
CN
Oxidation of cyclohexene (Chem. Lett. 1976 29)
Modified Prevost reaction (J. Chem. Soc., Chem. Comm. 1989 407)
Oxidative cleavage of epoxides with bismuth mandelate (Tetrahedron Lett. 1993 2601)
Bi2(SO4)3 (1.4 mol%)
EtCO2H, 65 °C, O2 (1 atm)via isomerization of peroxyradical?
CHO
90%
Bi(OAc)3, I2, AcOH
90 °C"reflux(dry system)
OAc
OAc
62"80%
Bi(OAc)3, I2, AcOH"H2O
90 °C"reflux(wet system)
OAc
OAc
70"95%+OAc
OH
cf. Ag, Hg, Tl
O
R1 R2
R1CO2H + R2CO2H
O
HO
10 mol% BiCl3t-BuOOH
CH3CN70 °C, 18 h
(80%)
O
HO O
Chemoselective allylic oxidation (Tetrahedron Lett. 2005 2581)
Dehydration (Tetrahedron Lett. 1994 5035)
OH Ph3BiBr2"I2
C6H12, RT2 h (87%)
cf. CrO3Cr(CO)6PDCRuCl3
toxic!
expensive!
BiIII"mandelate (10%)
DMSO, O2
(40"90%)
Ph3Bi(quant.)
OH
OH
O
O
+
"
"(4 h)
77%
Ph3Bi(quant.)
OH
OH
O
O
+
eg. of heterogeneous catalysis...
Jonathan LocknerBaran Group Meeting Bismuth in Organic Synthesis
F
Barbier/Grignard-type allylation (Wada Tetrahedron Lett. 1985 4211)• compatible with hydroxyl, carboxyl groups (Wada Tetrahedron Lett. 1986 4771)• can be conducted in aqueous media (Bull. Chem. Soc. Jpn. 1997 2265; Chem. Lett. 2002 376)• allyl alcohols can be employed (PBr3 or TMSCl!NaI; Bull. Chem. Soc. Jpn. 2000 689)
Mohan's variation: allylation of aldehydes (J. Org. Chem. 2005 2091)
Friedel!Crafts acylation (Tetrahedron Lett. 1997 8871; 2003 2037)
Mukaiyama!aldol reaction (Tetrahedron Lett. 1992 1053)
Mukaiyama!Michael addition (J. Org. Chem. 1993 1835)
Knoevenagel condensation (Chem. Lett. 1992 1945)
Diels!Alder cycloaddition (Dubac, J. Org. Chem. 1997 4880)
Erlenmeyer!Plochl synthesis of oxazolones (Synth. Comm. 2000 3167)
Rearrangement of epoxides (Tetrahedron Lett. 2001 8129)
Enone "-arylation (Tetrahedron Lett. 2001 781; J. Am. Chem. Soc. 2001 7451)
Enone #-arylation (Tetrahedron 2006 10594; J. Am. Chem. Soc. 2004 5350)
• see also Barton, J. Org. Chem. 1999 6915
Note: with BiIII, arylation at " position; with BiV, arylation at # position
HN
OO
O
(!)-paroxetinePaxil (GSK)
F
BnN
OPBu3(p-F-Ph)3BiCl2
i-Pr2NEtCH2Cl2!t-BuOH (9:1)
RT 3 h, 79%
BnN
O
R3
OH
R1 R2
BiCl3
Al, Zn or FeR3
O
X
R2
R1+
5% Bi(OTf)3•4H2O
solvent!free!
R
O+
XArH
R
O
Ar
Ph Ph
BiCl3!3NaI
CH2Cl2, )))Ph
Ph
OOTMS
+
OH O
R1
O
R2R1
BiCl3!3NaI
CH2Cl2, )))R4
OTMS
+
O
R3
HCl
MeOHR3
R2 O
R4
10% BiCl3
80 °C20!30 min
RE
O
E+E E
R
R2
R1
R3R4
O
10% BiCl3 or1% Bi(OTf)3
CH2Cl261-88%
R2
R1R3
R4
O
+
Ar
O
+
HNPh
OH
O
O
10% Bi(OAc)3
Ac2O, reflux 1 hN O
Ar O
Ph
OR1
Ar
R2
R3
0.1% Bi(OTf)3
CH2Cl2Ar
R3
O
R1R2
R1
OR2Bi(OTf)3
R1
OTMS+
R2OH or (R2OC)2O
(p-F-Ph)3BiCl2
BiCl3 Cl2p-F-PhMgBr
Ph3Bi
Rh(COD)2BF412 h 50 °C, air
THF-H2O (84%)
(65!78%)
O O
Ph
elemental Bi generated in situ
intermediacy of allyl bismuth species?
cf. AlCl3, etc.
HCl
MeOHNaI & ))) enhance catalytic power of BiCl3
BiCl3 $ soft Lewis acid catalyst for coupling and rearrangement reactions
#-amino acids
• higher reactivity/selectivity, comparable yields to Sc(OTf)3, Yb(fod)3, etc.• no polymerization (cf. strong LA's)• Bi(OTf)3 is not decomposed by H2O; can be recovered, reused• chiral Bi catalysts?? (TBD)
eg. of heterogeneous catalysis...
cf. BF3•Et2O
via aryl transfer to transient ("-phosphonio)enolate
Jonathan LocknerBaran Group Meeting Bismuth in Organic Synthesis
Reductive etherification (P. Andrew Evans, Org. Lett. 2003 3883)
Reductive etherification (J. Am. Chem. Soc. 2003 14702)
Synthesis of leucascandrolide A was reported at the ACS National Meeting, Sept 2006
Direct substitution of hydroxy group with amides (Angew. Chem. Int. Ed. 2007 409)
Biginelli reaction (Synlett 2001 863)
One-pot nucleoside synthesis (Synth. Comm. 1998 603)
Glycosylation via Ferrier rearrangement (Synthesis 2002 598)
Matano: oxazole synthesis via Bi ylides (J. Organomet. Chem. 2000 611 89)
Allylation of aldonitrones (New J. Chem. 2002 193)
Alkylation of amines via N-(alkylamino)benzotriazoles (Tetrahedron Lett. 1991 4247)
O
O
TESMeO OTBS
10 mol% BiBr3Et3SiH (1.4 equiv)
CH3CN, RT;then TBAF
93%
O
MeO OH(!)-centrolobine
MeO OTBS
"
"
complex mixture
O
O
TES
compare:
RO
OPMP
HO
O
BiBr3t-BuMe2SiH
CH3CN, 0 °C;
then 2,6-lutidineTMSOTf, 0 °C
93%
9O
OPMP
HO
9
(ds " 19:1)
(!)-mucocin
Me OR1
OOR2
CHO+ +H2N NH2
O
12 mol% BiCl3CH3CN
reflux, 5 h(72!95%)
NH
NH
OMe
R2
R1O
O
OOAc
AcO OAc
AcOTMSBr
5 mol% BiBr3CH2Cl2, 10 min
O
Br
AcO OAc
AcOO
base
AcO OAc
AcOsilylated base
BiBr3CH3CN, 4 h(65!80%)
ORO
RO
RO
+ R1
XH
(X = O, S)
5 mol% BiCl3
CH3CN, RT, 1!2 h(90!96%)
ORO
RO
XR1
R3 R1
OHR2
NuH (amide)5% Bi(OTf)3
5% KPF61,4-dioxane, RT
R3 R1
OHR2
"Bi"
R3 R1
NuR2
Ar3Bi
E
N
E
O
R
200 °C
5 min(92!96%)
O
N
R
E
E+ Ar3Bi
(quant.)
Bi powderNH4Cl (0.1 equiv)
DMF!H2OµW, 5 min (80!90%)
R3BrBiCl3!Al powder
THF!H2O, RT(34!87%)
Lewis acid or Bronsted acid catalysis?
solvolysis...
R1 R2
OSiR3 Ocat. BiBr3
Nu-SiR3 OR1
R2
NuOR1
NuR2
vs.
OCHO
O
+
Me
SiMe3 SiMe3
Me
OSiiPr3
BiBr3 (1 eq)CH3CN/CH2Cl2
Et3SiH, RT73%
O O
(ds " 99:1)
Tandem two-component etherification (J. Am. Chem. Soc. 2003 11456)
Sequential two-component cross-coupling followed by reductive etherification(J. Am. Chem. Soc. 2003 11456)
BiB
r 3 +
H2O
BiO
Br
+ H
Br
no preactivation (ROH # RX) required...
tolerates variety of FG's
$-anomer
cf. strong LA's (BF3•OEt2, SnCl4) and expensive triflates (Sc, Yb)
BiBr3 activates Si!X bond, converting TMSBr to halogenation reagent; then acts as LA catalyst, activating sugar for attack
better than using Hg
NN
N
NR1R2
NR1R2R3NN
N
OH
HNR1R2
! H2O
NOPh
ArH
+ BrN
OHPh
ArH
allylbismuth is generated, then treated with aldonitrone
Ar3BiCl2+
H2NCOR
KOtBu
CH2Cl2!50°C#RT
Ar3Bi=NCORDMAD
CH2Cl2RT!60°C
mechanism?
Jonathan LocknerBaran Group Meeting Bismuth in Organic Synthesis
OO
O
H OH
CH2OMe
H
(Ph3BiCl)2OCHCl3
RT 24 hno yield given
Cembranolide diterpenes (Aust. J. Chem. 1979 1273)
SS
HO
OH
OCOPh
Ph3BiCO3;
then NaBH4 HO
OH
S
S
H
OCOPh
25%
+HO
OCOPh
S
S
H
OH
50%
TMG, 85%
Maytansinoids: oxidative cleavage of vic-diol (Barton, JCSCC 1980 1089)
Carbapenems (Barton, ACIEE 1993 867)
N
MeO
S
Ph
OOTESTESO
TESOOTES
TBAF, THF, 0 °C;
then Ph3BiCO3CH3CN, reflux
N
MeO
CHO
S
Ph
O
N
MeO
CHO
Ph
O
+
mCPBACH2Cl2, 20°C;then PhMereflux, 80%
40%
20%
(D-glucosamine served as chiral auxiliary in Staudinger reaction for !-lactam synthesis)
"-arylation of phenols (Barton, Tetrahedron 1988 4483; JCSCC 1980 827)
OH
Me
Me
Me
Me
Ph5Bi
PhH, 82%
O
Me
Me
Me
Me
Ph
"-alkenylation of phenols and !-dicarbonyl compounds (Matano, J. Org. Chem. 2004 5505)
OH
Me MeO
MeMe
Ph
Ar3BiPh
BF4
NN
NH
PhMe(76%)
"-allylation of phenols and !-dicarbonyl compounds (Matano, Tetrahedron Lett. 1995 7475)
"-alkylation of phenols and !-dicarbonyl compounds (Matano, Organometallics 2000 2258)
[Ar3MeBi+][BF4#]
review of bismuthonium compounds: Bull. Chem. Soc. Jpn. 1996 2673
So far, bismuth has been under-utilized in natural product total synthesis. Prior to P. Andrew Evans' several total syntheses involving bismuth-mediated reductive etherification, only a few examples are to be found:
OO
O
CH2OMe
HO
mixture of 2° alcohols enone
"mild oxidant"
Ph3BiF2
BF3#OEt2CH2Cl2#78 °C
TMS
Ph3BiBF4
warm to RT(thermal decomp.)
Ph
source ofallyl electrophile
"...bismuth-mediated polarity inversion of allylsilanes."
nucleophile Nu
(e.g. e- rich arenes)
other Nu:PhS
Me2SPhSO2Ph3P
an exotic methylating agent?(high nucleofugality: Ph3Bi leaving ability is ~ 2X that of triflate)
Ph3BiCl2 + PhLi Ph5Bi(stable for months)
OPh4Bi
Ar3BiF2 + BF3•OEt2
R(HO)2B
NaBF4, H2O
Ar3BiPh
BF4
All of the above rely on the high nucleofugality of Ar3Bi (facile V $ III redox)
Ar3BiF2 + MeB(OH)2
BF3•OEt2
CH2Cl2
NaBF4
H2O