Bismuth in Organic Synthesis
Baran Group Meeting 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) Ph3Sn
R
replaced by:
Br
R
BiI3−Zn
• 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...
Jonathan Lockner
Bismuth in Organic Synthesis
Baran Group Meeting
Jonathan Lockner
Bi metal ($0.28/gm) general reviews: Mohan, Tetrahedron 2002 8373; Suzuki, Synthesis 1997 249
monographs: Organobismuth Chemistry, Suzuki & Matano, Elsevier 2001
BiX5
BiX3 (moisturesensitive, corrosive)
chapter: Main Group Metals in Organic Synthesis, Vol 2, Ch 14, Wiley 2001
BiR3 (air & light sensitive)
83rd element, the heaviest pnictogen (group 15) Ph3Bi $1.90/gm
ground state configuration: [Xe]4f145d106s26p3 (five valence electrons)
BiAr3 (stable crystalline solids)
most common oxidation states: +3, +5 in water, forms insoluble basic salts
Ph3BiCl2 $12.60/gm
Ar3BiX2
high nucleofugality -- like lead(IV) and iodine(III) Ph3Bi is better leaving group than OTf, owing to facile BiV/BiIII redox
Ar3RBiX (bismuthonium salts)
highly oxidizing, high Lewis acidity, especially for BiV centers
Ar3Bi=R (bismuthonium ylides)
(stability depends on substituents)
1934 ! Challenger (BiV) R'RCHOH
R'RC=O
1949 ! Rigby (NaBiO3, Bi2O3) 1960s ! industrial catalysts (Bi-Mo...)
CHO
+
late 1970s to 1980s ! Barton; Dodonov: oxidation & arylation with BiV
CN
$1.40 $8.00
mid 1980s ! Wada; Dubac: Barbier-type allylation & aldol with BiIII late 1980s ! bismuthonium salts and ylides... 1990s ! catalytic oxygenation, Friedel"Crafts acylation, etc.
N O K (2 equiv) Ar3BiCl2
O
N
Bi Ar O
Ar
Ar
Pyr
N Ar
O
Chem. Lett. 2005 11 1496 An Ullman-type coupling that doesn't involve copper, and even works with Ar = o-Tol
Bi BiCl3 BiBr3 Bi(OTf)3 Bi2O3 Bi(OAc)3 Bi(NO3)•5H2O Bi2(SO4)3 NaBiO3 Zn(BiO3)2
7440-69-9 7787-60-2 CAS # 88189-03-1 1304-76-3 22306-37-2 10035-06-0 CAS # 12232-99-4 CAS #
C, X, O, R C, X, R, M O C, X, R, M O X, O C, X, O, M O O, M O
Bu3Bi Ph3Bi Ph3BiCl2 Ph3Bi(OAc)2 Ph3BiCO3 Ph4BiOCOCF3
3692-81-7 603-33-8 594-30-9 7239-60-3 47252-14-2 83566-43-2
C, X C, X, O C, X, O C, X, O C, X, O C, X, O
C carbon-carbon X carbon-heteroatom O oxidation R reduction M miscellaneous
For any sort of addition or rearrangement, consider using catalytic BiCl3 or Bi(OTf)3
Bismuth in Organic Synthesis
Baran Group Meeting
Oxidation of cyclohexene (Chem. Lett. 1976 29) eg. of heterogeneous catalysis...
Oxidative cleavage of 1,2-diols (Barton, Tetrahedron 1986 5627) Ph3Bi (0.1 equiv) OH O NBS, K2CO3 Ph3Bi + (quant.) CH3CN, RT, 3 h OH (1% H2O) O 72% OH O " Ph3Bi + (quant.) " OH O (4 h) 77% O
NaBiO3 AcOH"H2O RT, 12 h
OH
Modified Prevost reaction (J. Chem. Soc., Chem. Comm. 1989 407)
cf. Ag, Hg, Tl
OH
Bi(OAc)3, I2, AcOH
OAc
90 °C"reflux (dry system)
OAc
Bi(OAc)3, I2, AcOH"H2O
OAc
62"80%
90 °C"reflux (wet system)
72%
O
90%
EtCO2H, 65 °C, O2 (1 atm) via isomerization of peroxyradical?
cf. Pb(OAc)4, NaIO4, MnO2
H
CHO
Bi2(SO4)3 (1.4 mol%)
Oxidative cleavage of !-ketols (J. Org. Chem. 1993 2196) O
Jonathan Lockner
OAc +
70"95% OH
OAc
Alcohol oxidation (ACIE 2002 3028) Oxidative cleavage of epoxides with bismuth mandelate (Tetrahedron Lett. 1993 2601)
(o-Tol)3BiCl2"DBU OH
CHO
PhMe, RT, 30 min
94% R1
Oxidation of acyloins to !-diketones (Rigby, J. Chem. Soc. 1951 793) O R
Bi2O3 R
OH
~100 °C, 15"30 min AcOH"EtOCH2CH2OH O
R
O
RSH
Zn(BiO3)2
(RS)2
R1SR2
PhMe, reflux
R1SOR2
HO (86"99%) (65"78%)
CHO
Bi"Mo"metal(s)"O NH3
CN
cf. BaMnO4, PCC Dehydration (Tetrahedron Lett. 1994 5035)
(0"85%)
Catalytic oxidation of hydrocarbons: propylene (Adv. Catal. 1994 233)
OH
O
10 mol% BiCl3 t-BuOOH CH3CN 70 °C, 18 h (80%)
(60"100%)
R1R2C=O
O2
R2CO2H
Chemoselective allylic oxidation (Tetrahedron Lett. 2005 2581)
R1R2C=O
R1R2C=NOH
+
DMSO, O2 (40"90%)
(60"95%)
Various oxidations using zinc bismuthate (Bull. Chem. Soc. Jpn. 1992 1131) R1R2CHOH
R1CO2H
R2
"superior to conventional oxidizing agents" presumed active species: Bi(OAc)3
O R
BiIII"mandelate (10%)
O
Ph3BiBr2"I2 C6H12, RT 2 h (87%)
HO
O
cf. CrO3 Cr(CO)6 toxic! PDC RuCl3 expensive!
Bismuth in Organic Synthesis
Baran Group Meeting
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) O + R1
R3
BiCl3
X
R3
Al, Zn or Fe
R2
Diels!Alder cycloaddition (Dubac, J. Org. Chem. 1997 4880) R1 + R2
OH
intermediacy of allyl bismuth species?
TMS
+
R1
X
+
5% Bi(OTf)3•4H2O
ArH
+
solvent!free !
Ph
BiCl3!3NaI
OTMS
R
OTMS
R1
R2
+
R4 R3
R
+
E
E
O
O
Ar
O
H N
Ph
OH
10% Bi(OAc)3
N
Ac2O, reflux 1 h
R1 O R2 0.1% Bi(OTf)3 R1 R2 R3 Ar Ar R3 CH2Cl2 O
CH2Cl2, )))
80 °C 20!30 min
E
Ph3Bi
O
#-amino acids
Ph
cf. BF3•Et2O
Ph
Ph NaI & ))) enhance catalytic power of BiCl3 O
HCl MeOH
O
Rh(COD)2BF4 12 h 50 °C, air THF-H2O (84%)
OH O
HCl
BiCl3!3NaI
10% BiCl3
O
Enone "-arylation (Tetrahedron Lett. 2001 781; J. Am. Chem. Soc. 2001 7451)
R2
O R4
R1 R3
BnN
PBu3 (p-F-Ph)3BiCl2
R
BiCl3 $ soft Lewis acid catalyst for coupling and rearrangement reactions
O
F
i-Pr2NEt BnN CH2Cl2!t-BuOH (9:1) RT 3 h, 79% via aryl transfer to transient ("-phosphonio)enolate
E (65!78%)
Ph
Enone #-arylation (Tetrahedron 2006 10594; J. Am. Chem. Soc. 2004 5350) • see also Barton, J. Org. Chem. 1999 6915
O
Knoevenagel condensation (Chem. Lett. 1992 1945) O
R4
Ar
Mukaiyama!Michael addition (J. Org. Chem. 1993 1835) O
R3
• 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)
Rearrangement of epoxides (Tetrahedron Lett. 2001 8129) eg. of heterogeneous catalysis...
cf. AlCl3, etc.
O
CH2Cl2, ))) MeOH
Ph
R2
O
Mukaiyama!aldol reaction (Tetrahedron Lett. 1992 1053) O
CH2Cl2 61-88%
R1
Friedel!Crafts acylation (Tetrahedron Lett. 1997 8871; 2003 2037)
R
+
Ar
R2OH or (R2OC)2O
O
R1
Erlenmeyer!Plochl synthesis of oxazolones (Synth. Comm. 2000 3167) O
OR2
Bi(OTf)3
10% BiCl3 or 1% Bi(OTf)3
O
Mohan's variation: allylation of aldehydes (J. Org. Chem. 2005 2091) O
R4
R3
elemental Bi generated in situ
R1 R2
Jonathan Lockner
p-F-PhMgBr
BiCl3
Cl2
O
O O
HN (!)-paroxetine Paxil (GSK)
(p-F-Ph)3BiCl2
Note: with BiIII, arylation at " position; with BiV, arylation at # position
F
Bismuth in Organic Synthesis
Baran Group Meeting
Jonathan Lockner
Biginelli reaction (Synlett 2001 863)
Tandem two-component etherification (J. Am. Chem. Soc. 2003 11456)
mechanism?
BiOBr + HBr
tolerates variety of FG's OSiR3
cat. BiBr3
O
R1
R2
vs.
Nu-SiR3
R1
O
R2 Nu
R1
O
Nu R2
O
+
Me
OR1
R2
CHO
O
+ H2N
Me
CHO
+
OSiiPr3 O Me SiMe3
O SiMe3
NH2
O
O
5 mol% BiBr3 OAc CH2Cl2, 10 min
AcO
AcO
NH
Me
BiBr3 CH3CN, 4 h (65!80%)
Br OAc
(ds " 99:1)
R2
R1O
One-pot nucleoside synthesis (Synth. Comm. 1998 603) $-anomer better than using Hg AcO AcO AcO OAc silylated base TMSBr O O
BiBr3 (1 eq) CH3CN/CH2Cl2 Et3SiH, RT 73%
O
reflux, 5 h (72!95%)
Lewis acid or Bronsted acid catalysis? Sequential two-component cross-coupling followed by reductive etherification (J. Am. Chem. Soc. 2003 11456)
BiBr3 + H2O
O
12 mol% BiCl3 CH3CN
N H
O
AcO
O
base
OAc
BiBr3 activates Si!X bond, converting TMSBr to halogenation reagent; then acts as LA catalyst, activating sugar for attack
Reductive etherification (P. Andrew Evans, Org. Lett. 2003 3883)
MeO
O TES
OTBS
compare: O TES
RO O
CH3CN, RT; then TBAF MeO 93%
O MeO
Glycosylation via Ferrier rearrangement (Synthesis 2002 598)
10 mol% BiBr3 Et3SiH (1.4 equiv)
O
RO OH
(!)-centrolobine
RO
R1
XH
5 mol% BiCl3
RO
O
CH3CN, RT, 1!2 h (X = O, S) (90!96%)
XR1
complex mixture OTBS
E
"
t
DMAD Ar3BiCl2 KO Bu Ar3Bi + Ar3Bi=NCOR CH Cl H2NCOR CH2Cl2 2 2 RT!60°C !50°C#RT
Reductive etherification (J. Am. Chem. Soc. 2003 14702) BiBr3 t-BuMe2SiH HO HO CH3CN, 0 °C; O O then 2,6-lutidine 9 RO 9 OPMP TMSOTf, 0 °C OPMP (ds " 19:1) 93%
(!)-mucocin
Direct substitution of hydroxy group with amides (Angew. Chem. Int. Ed. 2007 409) "Bi" R3
OH R2 R1
no preactivation (ROH # RX) required...
R3
Nu R2 R1
H
N
O
+
Br
N
Bi powder NH4Cl (0.1 equiv) DMF!H2O µW, 5 min (80!90%)
Ar
200 °C
E
Allylation of aldonitrones (New J. Chem. 2002 193)
Ph
Synthesis of leucascandrolide A was reported at the ACS National Meeting, Sept 2006
R3
+
O
Matano: oxazole synthesis via Bi ylides (J. Organomet. Chem. 2000 611 89)
"
solvolysis...
NuH (amide) OH 5% Bi(OTf)3 R2 R1 5% KPF6 1,4-dioxane, RT
cf. strong LA's (BF3•OEt2, SnCl4) and expensive triflates (Sc, Yb)
RO
R
5 min (92!96%)
R
O N
E E
O
allylbismuth is generated, then treated with aldonitrone Ph H
N
OH
Ar
Alkylation of amines via N-(alkylamino)benzotriazoles (Tetrahedron Lett. 1991 4247) N N N OH
HNR1R2
N
! H2O
N
R3Br BiCl3!Al powder
N NR1R2
THF!H2O, RT (34!87%)
R3
NR1R2
+
Ar3Bi (quant.)
Bismuth in Organic Synthesis
Baran Group Meeting
"-arylation of phenols (Barton, Tetrahedron 1988 4483; JCSCC 1980 827) OH Me
O Me
Me
Me
Ph5Bi
Me
PhH, 82%
Me
Ph3BiCl2 + PhLi
Ph Me
Ph4Bi
Ph5Bi (stable for months)
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: Cembranolide diterpenes (Aust. J. Chem. 1979 1273)
O
O
Me
Me
Me
Ar3Bi
N
Ph
N
O O H OH mixture of 2° alcohols
Ar3BiF2 + BF3•OEt2
BF4 O Me
(HO)2B
Me Ph
PhMe
(Ph3BiCl)2O CHCl3
O O
Ph
S
enone
"mild oxidant" Ph3BiCO3;
S
HO
OCOPh
then NaBH4 HO
OH
"-allylation of phenols and !-dicarbonyl compounds (Matano, Tetrahedron Lett. 1995 7475)
S
OH H OCOPh
Ph3BiF2
BF4
Ph3Bi BF3#OEt2 CH2Cl2 #78 °C
source of allyl electrophile
warm to RT (thermal decomp.)
nucleophile
(e.g.
e-
Nu
rich arenes)
HO
Ph other Nu: PhS Me2S PhSO2 Ph3P
Carbapenems (Barton, ACIEE 1993 867)
CH2Cl2
H2O
S 50%
Ph MeO
Ph MeO N
O TESO
S OTES
TBAF, THF, 0 °C;
O
then Ph3BiCO3 CH3CN, reflux
an exotic methylating agent? (high nucleofugality: Ph3Bi leaving ability is ~ 2X that of triflate) review of bismuthonium compounds: Bull. Chem. Soc. Jpn. 1996 2673
All of the above rely on the high nucleofugality of Ar3Bi (facile V $ III redox)
S
40% CHO + Ph
OTES O
[Ar3MeBi+][BF4#]
N
MeO TESO
Ar3BiF2 + MeB(OH)2
OCOPh H OH
TMG, 85%
"-alkylation of phenols and !-dicarbonyl compounds (Matano, Organometallics 2000 2258)
BF3•OEt2 NaBF4
S
+
S 25%
"...bismuth-mediated polarity inversion of allylsilanes." TMS
O
Maytansinoids: oxidative cleavage of vic-diol (Barton, JCSCC 1980 1089)
BF4 Ar3Bi
CH2OMe H
RT 24 h no yield given
NaBF4, H2O
(76%)
NH
R
O CH2OMe H
"-alkenylation of phenols and !-dicarbonyl compounds (Matano, J. Org. Chem. 2004 5505)
OH
Jonathan Lockner
mCPBA CH2Cl2, 20°C; then PhMe reflux, 80%
N
20% CHO (D-glucosamine served as chiral auxiliary in Staudinger reaction for !-lactam synthesis)
