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Home , Bismuth, Bismuth bronze

Baran Meeting in Organic Synthesis Jonathan Lockner

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 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 to make bronze... The use of bismuth facilitates the duplex process by which the tumi was made and forms an of unusual color." Science 1984 585

• specifically identified as a metallic element by 1753 (French chemist Claude François Geoffroy)

• heaviest "stable" element in , with only one "stable" : 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 (non-toxic and non-carcinogenic) (for instance, showcased at a 2006 IUPAC conference on green chemistry)

Ph Sn R replaced by: Br R 3 BiI3−Zn

• relatively rare: 64th in abundance, comparable to Ag and Cd

• soft, heavy, lustrous, silver- with an iridescent tinge

• serves as a suitable replacement for in fireworks, , etc.

"Dragon's eggs are pyrotechnic stars which first burn for a giving a visual effect then explode with a loud crackling report. Manufacture of this effect has become controversial due to the heavy 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... Baran Group Meeting Bismuth in Organic Synthesis Jonathan Lockner

Bi metal ($0.28/gm) general reviews: Mohan, Tetrahedron 2002 8373; Suzuki, Synthesis 1997 249

monographs: Organobismuth Chemistry, Suzuki & Matano, Elsevier 2001 BiX 5 BiX3 BiR3 (air & light sensitive) (moisture- chapter: Main Group Metals in Organic Synthesis, Vol 2, Ch 14, Wiley 2001 sensitive, corrosive)

83rd element, the heaviest (group 15)

14 10 2 3 ground state configuration: [Xe]4f 5d 6s 6p (five electrons) Ph3Bi $1.90/gm BiAr3 (stable crystalline )

most common oxidation states: +3, +5

in , forms insoluble basic salts Ph3BiCl2 $12.60/gm Ar3BiX2 high nucleofugality -- like lead(IV) and (III)

V III Ph3Bi is better leaving group than OTf, owing to facile Bi /Bi Ar3RBiX Ar3Bi=R highly oxidizing, high Lewis acidity, especially for BiV centers (bismuthonium salts) (bismuthonium ylides) (stability depends on substituents) 1934 ! Challenger (BiV) R'RCHOH R'RC=O

1949 ! Rigby (NaBiO3, Bi2O3)

1960s ! industrial catalysts (Bi-Mo...) CHO + CN Bi 7440-69-9 C, X, O, R $1.40 BiCl3 7787-60-2 C, X, R, M V late 1970s to 1980s ! Barton; Dodonov: oxidation & arylation with Bi BiBr3 CAS # O $8.00 Bi(OTf)3 88189-03-1 C, X, R, M C carbon-carbon mid 1980s ! Wada; Dubac: Barbier-type allylation & aldol with BiIII Bi2O3 1304-76-3 O Bi(OAc) X carbon-heteroatom 3 22306-37-2 X, O O oxidation Bi(NO )•5H O late 1980s ! bismuthonium salts and ylides... 3 2 10035-06-0 C, X, O, M R reduction Bi2(SO4)3 CAS # O M miscellaneous NaBiO3 12232-99-4 1990s ! catalytic oxygenation, Friedel"Crafts acylation, etc. Zn(BiO ) O, M 3 2 CAS # O Bu Bi 3 3692-81-7 C, X Ph3Bi 603-33-8 Ph3BiCl2 C, X, O N O O N 594-30-9 C, X, O Ph3Bi(OAc)2 7239-60-3 K Ar Ph BiCO C, X, O (2 equiv) Bi Ar 3 3 47252-14-2 Ar N O Ph4BiOCOCF3 C, X, O Ar3BiCl2 O 83566-43-2 Pyr Ar C, X, O Chem. Lett. 2005 11 1496 An 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 Baran Group Meeting Bismuth in Organic Synthesis Jonathan Lockner

Oxidative cleavage of 1,2-diols (Barton, Tetrahedron 1986 5627) Oxidation of cyclohexene (Chem. Lett. 1976 29) eg. of heterogeneous catalysis... Ph Bi (0.1 equiv) OH 3 O CHO NBS, K2CO3 Bi2(SO4)3 (1.4 mol%) Ph Bi + 3 90% CH3CN, RT, 3 h (quant.) EtCO2H, 65 °C, O2 (1 atm) OH (1% H2O) O via isomerization of peroxyradical? 72% OH O Modified Prevost reaction (J. Chem. Soc., Chem. Comm. 1989 407) " + Ph3Bi cf. Ag, Hg, Tl (quant.) " Bi(OAc)3, I2, AcOH OAc OH (4 h) O 77% 62"80% 90 °C"reflux Oxidative cleavage of !-ketols (J. Org. Chem. 1993 2196) (dry system) OAc O O NaBiO cf. Pb(OAc) , NaIO , MnO 3 H 4 4 2 Bi(OAc)3, I2, AcOH"H2O OAc OAc OH + 70"95% OH AcOH"H2O 72% 90 °C"reflux O OH RT, 12 h (wet system) OAc Alcohol oxidation (ACIE 2002 3028)

(o-Tol)3BiCl2"DBU Oxidative cleavage of epoxides with bismuth mandelate (Tetrahedron Lett. 1993 2601) CHO OH PhMe, RT, 30 min 94% O BiIII"mandelate (10%) R1CO2H + R2CO2H R1 R2 Oxidation of acyloins to !-diketones (Rigby, J. Chem. Soc. 1951 793) DMSO, O2 (40"90%) O O "superior to conventional oxidizing agents" Bi2O3 R presumed active species: Bi(OAc)3 R R ~100 °C, 15"30 min R Chemoselective allylic oxidation (Tetrahedron Lett. 2005 2581) OH (60"95%) AcOH"EtOCH2CH2OH O O O 10 mol% BiCl cf. CrO3 3 toxic! Various oxidations using bismuthate (Bull. Chem. Soc. Jpn. 1992 1131) t-BuOOH Cr(CO)6 PDC CH3CN RuCl3 expensive! R1R2CHOH R1R2C=O (60"100%) 70 °C, 18 h HO O HO (80%) RSH Zn(BiO ) (RS) (86"99%) 3 2 2 cf. BaMnO4, PCC R1SR2 PhMe, reflux R1SOR2 (65"78%) Dehydration (Tetrahedron Lett. 1994 5035)

R1R2C=NOH R1R2C=O (0"85%) OH Ph3BiBr2"I2 Catalytic oxidation of hydrocarbons: propylene (Adv. Catal. 1994 233)

C6H12, RT CHO 2 h (87%) O2

Bi"Mo"metal(s)"O CN NH3 Baran Group Meeting Bismuth in Organic Synthesis Jonathan Lockner

Diels!Alder cycloaddition (Dubac, J. Org. Chem. 1997 4880) Barbier/Grignard-type allylation (Wada Tetrahedron Lett. 1985 4211) • higher reactivity/selectivity, compatible with hydroxyl, carboxyl groups (Wada Tetrahedron Lett. 1986 4771) • comparable yields to Sc(OTf)3, can be conducted in aqueous media (Bull. Chem. Soc. Jpn. 1997 2265; Chem. Lett. 2002 376) 10% BiCl3 or R • R1 1 Yb(fod)3, etc. allyl alcohols can be employed (PBr3 or TMSCl NaI; Bull. Chem. Soc. Jpn. 2000 689) 1% Bi(OTf)3 R • ! + R 3 • no polymerization (cf. strong LA's) R 4 R4 R 3 CH Cl R2 • Bi(OTf)3 is not decomposed by OH 2 2 2 O O 61-88% O H2O; can be recovered, reused BiCl3 elemental Bi generated in situ chiral Bi catalysts?? (TBD) + R X • R 1 R3 3 Al, Zn or Fe intermediacy of allyl bismuth species? Erlenmeyer!Plochl synthesis of oxazolones (Synth. Comm. 2000 3167) R1 R2 R2 O Ar O O H Mohan's variation: allylation of aldehydes (J. Org. Chem. 2005 2091) Ph N 10% Bi(OAc)3 + OH N O #-amino OR Ar Ac O, reflux 1 h O Bi(OTf) 2 O 2 TMS 3 Ph + R R1 1 R2OH or (R2OC)2O Rearrangement of epoxides (Tetrahedron Lett. 2001 8129) eg. of heterogeneous catalysis... Friedel!Crafts acylation (Tetrahedron Lett. 1997 8871; 2003 2037) R cf. BF Et O R O R 0.1% Bi(OTf)3 R1 2 3• 2 1 2 R O cf. AlCl3, etc. Ar 3 5% Bi(OTf)3•4H2O O Ar R + ArH 3 CH2Cl2 R X O solvent!free R Ar ! Enone "-arylation (Tetrahedron Lett. 2001 781; J. Am. Chem. Soc. 2001 7451) Mukaiyama!aldol reaction (Tetrahedron Lett. 1992 1053) O Ph3Bi O

O OH O Rh(COD) BF OTMS BiCl3!3NaI HCl 2 4 + 12 h 50 °C, air Ph Ph Ph THF-H O (84%) Ph Ph CH2Cl2, ))) MeOH 2 NaI & ))) enhance Enone -arylation (Tetrahedron 2006 10594; J. Am. Chem. Soc. 2004 5350) catalytic power of BiCl3 # Mukaiyama!Michael addition (J. Org. Chem. 1993 1835) • see also Barton, J. Org. Chem. 1999 6915 O R O PBu F O OTMS BiCl 3NaI 2 O 3 O O F 3! HCl (p-F-Ph) BiCl O + 3 2 R1 R4 R1 R2 R4 CH2Cl2, ))) MeOH O R3 i-Pr2NEt R3 BnN BnN CH2Cl2!t-BuOH (9:1) HN Knoevenagel condensation (Chem. Lett. 1992 1945) RT 3 h, 79% (!)-paroxetine via aryl transfer to transient ("-phosphonio)enolate Paxil (GSK) O 10% BiCl3 E E BiCl Cl + E E 3 2 R (65!78%) p-F-PhMgBr (p-F-Ph)3BiCl2 80 °C R 20!30 min

Note: with BiIII, arylation at " position; with BiV, arylation at # position BiCl3 $ soft Lewis catalyst for coupling and rearrangement reactions Baran Group Meeting Bismuth in Organic Synthesis Jonathan Lockner

Tandem two-component etherification (J. Am. Chem. Soc. 2003 11456) Biginelli reaction (Synlett 2001 863) mechanism? tolerates variety of FG's r 12 mol% BiCl3 O R2 B cat. BiBr3

H OSiR3 O vs. CH3CN O O O R O NH + CHO 1 R Nu + + r R R Nu-SiR3 R O 2 R O R2 B 1 2 1 1 H N NH reflux, 5 h Nu R2 Me OR1 2 2 Me N O

O i (7295%) H

B Lewis acid or Bronsted acid catalysis?

Sequential two-component cross-coupling followed by reductive etherification One-pot nucleoside synthesis (Synth. Comm. 1998 603) (J. Am. Chem. Soc. 2003 11456) better than using Hg -anomer AcO AcO base AcO OAc silylated base O BiBr3 (1 eq) O TMSBr O

O

2 CH CN/CH Cl i 3 2 2 H + OSi Pr 3 5 mol% BiBr3 Br BiBr3 + CHO

3 Me O O Me Et3SiH, RT O O CH Cl , 10 min CH3CN, 4 h AcO OAc r AcO OAc 2 2 AcO OAc

B 73% (6580%) i SiMe3 SiMe3 (ds 99:1)

B BiBr3 activates SiX bond, converting TMSBr to halogenation reagent; then acts as LA catalyst, activating sugar for attack Reductive etherification (P. Andrew Evans, Org. Lett. 2003 3883) Glycosylation via Ferrier rearrangement (Synthesis 2002 598) cf. strong LA's (BF3•OEt2, SnCl4) and 10 mol% BiBr3 O RO RO expensive triflates (Sc, Yb) Et3SiH (1.4 equiv) O 5 mol% BiCl3 O RO XH TES CH CN, RT; + RO MeO OTBS 3 O R1 O then TBAF MeO OH CH3CN, RT, 12 h (X = O, S) 93% ()-centrolobine RO (9096%) XR compare: 1 O " Matano: oxazole synthesis via Bi ylides (J. Organomet. Chem. 2000 611 89) O complex mixture TES E MeO OTBS " KOtBu E 200 °C O E Ar3BiCl2 DMAD R solvolysis... Ar3Bi + Ar3Bi + Ar3Bi=NCOR (quant.) H NCOR CH Cl CH Cl N R 5 min N Reductive etherification (J. Am. Chem. Soc. 2003 14702) 2 2 2 2 2 (9296%) E 50°CRT RT60°C BiBr3 O t-BuMe2SiH HO HO CH CN, 0 C; 3 ° Allylation of aldonitrones (New J. Chem. 2002 193) O ()-mucocin allylbismuth is generated, O RO then 2,6-lutidine 9 then treated with aldonitrone 9 Bi powder OPMP TMSOTf, 0 °C OPMP Ph OH 93% (ds 19:1) Ph O NH4Cl (0.1 equiv) N N + Br Synthesis of leucascandrolide A was reported at the ACS National Meeting, Sept 2006 DMFH2O H H Ar µW, 5 min (8090%) Ar Direct substitution of hydroxy group with amides (Angew. Chem. Int. Ed. 2007 409) Alkylation of amines via N-(alkylamino)benzotriazoles (Tetrahedron Lett. 1991 4247)

NuH (amide) R3Br "Bi" N N OH 5% Bi(OTf) OH Nu HNR1R2 BiCl3Al powder 3 N N NR R R2 R R2 1 2 2 N R3 R3 R R3 N H2O THFH O, RT R1 5% KPF6 3 R1 R1 2 1,4-dioxane, RT OH NR1R2 (3487%) no preactivation (ROH RX) required... Baran Group Meeting Bismuth in Organic Synthesis Jonathan Lockner

So far, bismuth has been under-utilized in natural product total synthesis. Prior to P. Andrew "-arylation of phenols (Barton, Tetrahedron 1988 4483; JCSCC 1980 827) Evans' several total syntheses involving bismuth-mediated reductive etherification, only a few examples are to be found: OH O Ph3BiCl2 + PhLi Ph5Bi Ph (stable for months) Me Me Me Ph5Bi Me Ph Bi Cembranolide diterpenes (Aust. J. Chem. 1979 1273) 4 O O O Me Me PhH, 82% Me Me (Ph BiCl) O CH2OMe 3 2 CH2OMe H CHCl3 H "-alkenylation of phenols and !-dicarbonyl compounds (Matano, J. Org. Chem. 2004 5505) O O RT 24 h O OH O O Ar BiF + BF •OEt H no yield given BF 3 2 3 2 4 mixture of 2° alcohols enone OH Ar Bi O (HO)2B 3 Ph Me R Me Me Me Maytansinoids: oxidative cleavage of vic-diol (Barton, JCSCC 1980 1089) Ph NaBF , H O N N 4 2 OH OCOPh PhMe "mild oxidant" (76%) S S H H NH BF4 Ph BiCO ; 3 3 OCOPh OH Ar3Bi S + S Ph then NaBH HO OCOPh 4 HO HO S S OH "-allylation of phenols and !-dicarbonyl compounds (Matano, Tetrahedron Lett. 1995 7475) 25% 50% "...bismuth-mediated polarity inversion of allylsilanes." TMG, 85% TMS BF Ph BiF 4 3 2 Ph3Bi Ph Carbapenems (Barton, ACIEE 1993 867) Ph warm to RT BF3#OEt2 MeO CH Cl source of (thermal decomp.) 2 2 allyl electrophile S #78 °C other Nu: Ph N PhS MeO O nucleophile Nu TBAF, THF, 0 °C; CHO Me2S S 40% mCPBA - (e.g. e rich arenes) PhSO2 N O CH2Cl2, 20°C; Ph3P then Ph3BiCO3 + OTES CH CN, reflux then PhMe TESO 3 Ph reflux, 80% "-alkylation of phenols and !-dicarbonyl compounds (Matano, Organometallics 2000 2258) MeO TESO OTES N O BF3•OEt2 NaBF4 CHO + # 20% Ar3BiF2 + MeB(OH)2 [Ar3MeBi ][BF4 ] (D-glucosamine served as chiral auxiliary in Staudinger reaction for !-lactam synthesis) CH2Cl2 H2O 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)