Tellurium (Te) in Organic Synthesis

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Tellurium (Te) in organic synthesis

Reporter: Lin Deng Supervisor: Guangbin Dong Date: Jan 28. 2014

Petragnani, N.; Stefani, H. A. Tellurium in Organic Synthesis, 2nd ed.; Academic Press: London, 2007. Else_TOS-PETRAGNANI_ch001.qxd 12/4/2006 5:46 PM Page 1

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Introduction

1.1 SOME PHYSICAL PROPERTIES OF TELLURIUM

The Pauling electronegativities of carbon and tellurium are, respectively, 2.5 and 2.1. This, in addition to the large volume of the tellurium atom (atomic radius 1.37, ionic radius 2.21), promotes easy polarization of Te–C bonds. The ionic character of the bonds increases in the order C(sp3)ϪTeϾC(sp2)ϪTeϾC(sp)ϪTe, in accordance with the electronegativity of carbon accompanying the s character (Table 1.1). BriefThe TeϪC bondintroduction therefore exhibits a high reactivity, to Tellurium as demonstrated typically (Te by )the easy heterolytic cleavage towards nucleophilic reagents.

1.2 RELEVANT MONOGRAPHS AND REVIEW ARTICLES

1. Rheinboldt, H. in Houben-Weyl-Methoden der Organischen Chemie (ed. E. Muller). 4th edn, Vol. IX. Georg Thieme, Stuttgart, 1955. 2. Petragnani, N.; Moura Campos, M. Organomet. Chem. Rev. 1967, 2, 61. 3. Cooper, W. C. (ed.). Tellurium. Van Nostrand Rheinhold, New York, 1971. 4. Irgolic, K. J.; Zingaro, R. in Organometallic Reactions (eds. E. Becker; M. Tsutsui). Wiley, New York, 1971. 5. Irgolic, K. J. The Organic Chemistry of Tellurium. Gordon and Breach, New York, 1974. 6. Irgolic, K. J. J. Organomet. Chem. 1975, 103, 91. lrgolic, K. J. J. Organomet. Chem. 1977, 130, 411. Irgolic, K. J. J. Organomet. Chem. 1978, 158, 235; Irgolic, K. J. J. Organomet. Chem. 1980, 189, 65. Irgolic, K. J. J. Organomet. Chem. 1980, 203, 368.

Table 1.1

Some physical properties of the VIA family of elements Element Atomic Atomic Electronic Pauling Ionization Ionic Atomic number mass configuration electronegativity potential radius radius

O 8 15.99 1s22s22p4 3.5 13.61 1.40 0.66 S 16 32.06 2s22p63s23p4 2.5 10.36 1.84 1.04 Se 34 78.96 3s23p63d104s24p4 2.4 9.75 1.98 1.17 Te 52 127.6 4s24p64d105s25p4 2.1 9.01 2.21 1.37

• 2.5 for carbon & 1large volume atom • easily polarize Te-C bonds • Highly reactive 2 Tellurium (Te) in organic synthesis

• Several important types of reactions • Reductions • Tellurium-Mediated Formation of anion species and their reactions with electrophiles • Organotellurium-based ring closure reactions

• Remove the Tellurium • With formation of new C-C bonds • With formation of other functionalities

• Application of Tellurium chemistry • Vinylic tellurides • Free radical chemistry

3 with deuterium, 100%PhCHDOD is Reductions observed

aliphatic ketones and esters are not • Reduction of carbonyl compounds applicable • Using hydrogen telluride

Kambe, N.; Kondo, K.; Morita, S.; Murai, S.; Sonoda, N. Angew. Chem. 1980, 92, 1009. • Using phenyl telluride

(1) Akiba, M.; Cava, M. P. Synth. Commun. 1984, 12, 1119. (2) Aso, Y.; Ogura, F. et al. Nippon Kagaku Kashi 1987, 1490.

Aliphatic ketones and esters are not applicable

4 Reductions • Using phenyl telluride

Q1: Why the reaction will give ether instead of alcohol as product in the presence of zinc iodide?

Nagakawa, K.; Osuka, M.; Sasaki, K.; Aso, Y.; Otsubo, T.; Ogura, F. Chem. Lett. 1987, 1331.

5 Reductions • Using other tellurides

Ti (III) as reducing reagent; DCM Coupling mechanism is unclear

Suzuki, S. H.; Manabe, H.; Enokiya, R.; Hanazaki, Y. Chem. Lett. 1986, 1339.; Suzuki, H.; Hanazaki, Y. Chem. Lett. 1986, 549.

Me N O

H NMP

Suzuki, H.; Nakamura, T. J. Org. Chem. 1993, 58, 241.

• Deuterium experiments

• Mechanism involves radical intermediate generate Ti(III) to reduce the carbonyl group

6 Reductions

• Selective Reduction of α,β-unsaturated carbonyl compounds

Kambe, N.; Kondo, K.; Morita, S.; Murai, S.; Sonoda, N. Angew. Chem. 1980, 92, 1009.; Akiba, M.; Cava, M. P. Synth. Commun. 1984, 12, 1119 • Reduction of conjugated arylalkenes and arylalkynes

• Works well with terminal alkenes

acceptable yield

(1) Akiba, M.; Cava, M. P. Synth. Commun. 1984, 12, 1119. (2) Aso, Y.; Ogura, F. et al. Nippon Kagaku Kashi 1987, 1490.

7 Reductions

• Reduction of imines and enamines

Kambe, N.; Inagaki, T.; Miyoshi, N.; Ogawa, A.; Sonoda, N. Chem. Lett. 1987, 7, 1275. • Reductive desulphuration and reduction of nitro groups

Suzuki, H.; Manabe, H.; Kawaguchi, T.; Inouye, M. Bull. Chem. Soc. Jpn. 1987, 60, 771

8 Reductions • Reductive desulphuration and reduction of nitro groups

• Protic solvent — higher reducing ability

• Aprotic solvent — Azo compounds

• Steric hindered nitro compounds are easier to be reduced

• More practical condition

Suzuki, H.; Manabe, H.; Inouye, M. Chem. Lett. 1985, 1671. Osuka, A.; Shimizu, H.; Suzuki, H. Chem. Lett. 1983, 1373.

Akiba, M.; Cava, M. P. Synth. Commun. 1984, 14, 1119. Uchida, S.; Yanada; K.; Yamaguchi, H.; Meguri, H. Chem. Lett. 1986, 1069. 9 Reductions • Debromination

• Application of this reactions

Kambe, N.; Tsukamoto, T.; Miyoshi, N.; Murai, S.; Sonoda, N. Bull. Chem. Soc. Jpn. 1986, 59, 3013. 10 Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 147

4.2 TELLURIUM-MEDIATED FORMATION OF ANIONIC SPECIES 147

Chemistry.p. 309. Plenum Press, London, 1973. Mathai, I. M.; Schug, K.; Miller, S. I. J. Org. Chem. 1970, 35, 1733. Gordon, J. E.; Chang, V. S. K. J. Org. Chem. 1973, 38, 3062 and references therein. 42. Moura Campos, M.; Petragnani, N. Tetrahedron Lett. 1960, 5. 43. Suzuki, H.; Kondo, A.; Osuka, A. Bull. Chem. Soc. Jpn. 1985, 58, 1335. 44. Butcher, T. S.; Detty, M. R. J. Org. Chem. 1998, 63, 177. 45. Leonard, K. A.; Zhou, F.; Detty, M. R. Organometallics 1996, 15, 4285. 46. Petragnani, N.; Moura Campos, M. Chem. Ber. 1961, 94, 1759. 47. Ramasamy, K.; Kalyanasundaram, S. K.; Shanmugam, P. Synthesis 1978, 311. 48. Suzuki, S.; Inouye, M. Chem. Lett. 1985, 225. 49. Huang, K.; Hou, Y. Q. Synth. Commun. 1988, 18, 2201. 50. Engman, L. Tetrahedron Lett. 1982, 23, 3601. 51. Li, C. J.; Harp, D. N. Tetrahedron Lett. 1990, 31, 6291. 52. Einstein, F. B. W.; Jones, C. H. W.; Jones, T.; Sharma, R. D. Can. J. Chem. 1983, 61, 2611. 53. Engman, L.; Bystrom, S. E. J. Org. Chem. 1985, 50, 3170. 54. Kambe, N.; Tsukamoto, T.; Miyoshi, N.; Murai, S.; Sonoda, N. Bull. Chem. Soc. Jpn. 1986, 59, 3013. 55. Bargues, V.; Blay, G.; Fernandez, J.; Pedro, J. R. Synlett 1996, 655. 56. See methods reported in refs. 57–60. 57. Osuka, A.; Suzuki, H. Chem. Lett. 1983, 119. 58. Clive, D. L. J.; Beaulieu, P. L. J. Org. Chem. 1982, 47, 1124. 59. Engman, L.; Cava, M. P. J. Org. Chem. 1982, 47, 3946. 60. Li, C. J.; Harp, D. N. Tetrahedron Lett. 1991, 32, 1545. 61. Mack, W. Angew. Chem. 1967, 6, 1083. 62. Luppold, E.; Winter, W. Chem. Ztg. 1977, 101, 303. 63. Osuka, A.; Takechi, K.; Suzuki, H. Bull. Chem. Soc. Jpn. 1984, 57, 303. 64. Suzuki, H.; Takaoka, K.; Ogura, A. Bull. Chem. Soc. Jpn. 1985, 58, 1067. 65. Huang, X.; Pi, J. H. Synth. Commun. 1990, 20, 2297. 66. Huang, X.; Pi, J. H.; Huang, Z. Phosphorus Sulfur Silicon 1992, 67, 177. 67. Padmanabhan, S.; Ogawa, T.; Suzuki, H. J. Chem. Res. (S) 1989, 266. 68. Li, C. J.; Harpp, D. N. Tetrahedron Lett. 1993, 34, 903. 69. Li, C. J.; Harpp, D. N. Tetrahedron Lett. 1992, 33, 7293.

4.2 TELLURIUM-MEDIATED FORMATION OF ANIONIC SPECIES AND THEIR REACTIONS WITH ELECTROPHILES

4.2.1Formation Reformatsky-type of reactionsanion species and their reactions Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 148 By treatment with sodium telluride,with bromoacetic electrophiles esters react with aromatic and non-eno- lizable• Reformatsky aldehydes in aprotic-type solvents, reactions giving α,β-unsaturated esters.1,2

Na Te/DMF/THF R 1 2 Br CO2R + RCHO 1 In accordance 148-10°C (37-73%) 4. TELLURIUM IN COORGANICR SYNTHESIS 2 with normal mechanism, 1 O In accordanceR = Me, withEt; R a = Reformatsky Ph, o -Me, reactionp -Me2N, mechanism, p -Cl, p -FC the6H 4 telluride, ion attacks theTe(-2) as bromine atom to generate an ester enolate which reacts in sequence Owith the aldehyde to PhCH = CH, Me2CPh, Me2C=CH(CH2)2CMe=CH anion afford the α,β-unsaturated ester.

O- O O- 2- 1 1 Te Br CO2R - R OR -TeBr R1O R O

+ O H3O R OR1

TeBr- Te + Br-

The reaction exhibits the following features: chloroacetates give lower yields than bro- moacetates; the E configuration is observed for the formed CϭC bond; α,β-unsaturated carbonyl compounds• E configuration lead only to 1,2-addition of double products; bond; ketones are unreactive under the described conditions;• for αa ,largeβ-unsaturated excess of the carbonylbromoacetate, only and 1,2-additionsodium telluride is required to assure high conversions.• ketone is not applicable • need large excess of bromoacetate and sodium telluride 1 Reformatsky-type reaction (typical procedure). To a solution of Na2Te (prepared from tellurium (0.7 g, 4 mmol), NaH (0.20 g, 8.6 mmol) and DMF (7 mL) by heating at 140°C for 30 min under N , is added dropwise at −20°C a solution of benzaldehyde (0.10 g, 1 mmol) 2 Suzuki, S.; Inouye, M. Chem. Lett. 1986, 403. in THF (1.5 mL) followed by ethyl bromoacetate (0.67 g, 4 mmol) in THF (1.5 mL). 11 Tellurium precipitates instantaneously. After stirring for 1 h, 0.5 M H2SO4 (5 mL) satu- rated with NaCl is added followed by Et2O (10 mL). Excess Na2Te is destroyed by expos- ing the mixture to air and stirring for 1 h. The mixture is filtered through Celite®,the

organic phase is separated, and the aqueous layer extracted twice with Et2O. The combined extracts are washed with brine, dried (Na2SO4) and evaporated, leaving a yellow oil, which is purified by Kügelrohr distillation under reduced pressure to give ethyl cinnamate (0.10 g (60%); b.p. 95–110°C/1.5 torr). Haloacetonitrile and p-cyanobenzyl bromide react similarly, leading to α,β-unsaturated nitriles2 accompanied by minor amounts of the alcohols.

Na2Te/DMF/THF X CN + RCHO R CN ( + ROH) 0°C (31-70%) O X = Cl, Br; R = Ph, p -ClC6H4, PhCH=CH, O

same Br C H CN-p + RCHO R C6H4CN-p 6 4 conditions O R= O

The previously described diisobutyl telluride/titanium(IV) system (see Section 4.1.1.3) also promotes similar Reformatsky-type reactions.3 In this case, however, the products are Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 148

148 4. TELLURIUM IN ORGANIC SYNTHESIS

In accordance with a Reformatsky reaction mechanism, the telluride ion attacks the bromine atom to generate an ester enolate which reacts in sequence with the aldehyde to afford the α,β-unsaturated ester.

O- O O- 2- 1 1 Te Br CO2R - R OR -TeBr R1O R O

+ O H3O R OR1

TeBr- Te + Br-

1 Reformatsky-type reaction (typical procedure). To a solution of Na2Te (prepared from tel- Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 149 lurium (0.7 g, 4 mmol), NaH (0.20 g, 8.6 mmol) and DMF (7 mL) by heating at 140°C for 30 min under N2, is added dropwise at −20°C a solution of benzaldehyde (0.10 g, 1 mmol) in THF (1.5 mL) followed by ethyl bromoacetate (0.67Else_TOS-PETRAGNANI_Ch004.qxd g, 4 mmol) in THF (1.5 mL). 12/12/2006 6:51 PM Page 149 Tellurium precipitates instantaneously. After stirring for 1 h, 0.5 M H SO (5 mL) satu- Else_TOS-PETRAGNANI_Ch004.qxd2 4 12/12/2006 6:51 PM Page 149 rated with NaCl is added followed by Et2O (10 mL). Excess Na2Te is destroyed by expos- ing the mixture to air and stirring for 1 h. The mixture is filtered through Celite®,the organic phase is separated,4.2 TELLURIUM-MEDIATED and the aqueous layer FORMATION extracted twice OF ANIONIC with Et O. SPECIES The combined 149 Formation of anion species2 and their reactions extracts are washed with brine, dried (Na2SO4) and evaporated, leaving a yellow oil, which is purified by Kügelrohr distillation under reduced pressure to give4.2 ethyl TELLURIUM-MEDIATED cinnamate (0.10 FORMATION OF ANIONIC SPECIES 149 β-chloroesters. with electrophiles g (60%); b.p. 95–110°C/1.5 torr). 4.2 TELLURIUM-MEDIATED FORMATION OF ANIONIC SPECIES 149 Haloacetonitrile and• pReformatsky-cyanobenzyl bromide-type react reactions similarly, leading to -unsaturated -chloroesters.α,βCl 2 i -Br2Te/TiClβ 4 nitriles accompanied by minor amounts of the alcohols. CO2Et Br CO2Et + RCHO β-chloroesters.Ph CH Cl / /(66%) 2 2 Cl Na Te/DMF/THF i -Br2Te/TiCl4 Cl CO Et 2 i -Br2Te/TiCl4 2 X CN R CN ( + ROH) Br CO2Et + RCHO Ph CO2Et The described+ RCHO protocol was later improved by the use of the systemBr PhTeLi/CeCl CO2Et + RCHO3. Ph CH2Cl2/ /(66%) 0°C (31-70%) CH2Cl2/ /(66%) PhTeLi (5.0O mmol)-CeCl (2.5 mmol) Suzuki,OH H.; Manabe, H.; Enokiya, R.; Hanazaki, Y. Chem. Lett. 1986,1339. X = Cl, Br; R = Ph, p -ClC H 1, PhCH=CH, The3 describedThe described protocol1 protocol was was later later improved improved byby the useuse of of the the system system PhTeLi/CeCl PhTeLi/CeCl3. 3. EtO2CCH2Br +6 RR4 CO R RC CH2CO2Et Oether, 0°C - r.t., 1 h PhTeLi (5.0 mmol)-CeCl (2.5 mmol) OHOH (47-95%) 1 PhTeLi (5.0 mmol)-CeCl33 (2.5 mmol) 1 1 EtO2CCH2Br +1 RR CO R RC1 CH2CO2Et R = Ph; R = Me, Et same EtO2CCH2Br + RR CO ether, 0°C - r.t., 1 h R RC CH2CO2Et Br C6H4CN-p + RCHO1 R C6H4CN-p ether, 0°C - r.t., 1 h R = Me; R = C5H11conditions (47-95%) R = Ph; R1 = Me, Et (47-95%) 1 1 R, R = (CH2)5, O R = Ph; R = Me,1 Et O R = Me; R = C5H11 R = Me; R11 = C H R= R, R = (CH52)511, O O R = R1 = PhCH2, i -pr 1 R, R = (CH2)5, O R = R1 = PhCH2, i -pr Suzuki, H.; Manabe, H.; Inouye, M. Nippon Kagaku Kaishi 1987, 1485. 1 The previously describedR, diisobutyl R = telluride/titanium(IV) system (seeR =Section R1 = PhCH 4.1.1.3)2, i -pr also promotes similar Reformatsky-type reactions.3 In this case, however, theR, products R1 = are The following scheme rationalizes the reaction.4 R, R1 = The following scheme rationalizes the reaction.4

CeCl3 1 CeCl 4 O OCeCl The followingRRC schemeCOEt rationalizes3 the reaction. 1 H 2 H O OCeCl2 RRC COEt H CC Br C C 2 O Br CO C • applicableH2CC to ketoneO O OEt OEt Ce CeClOEt3 OEt Ce H OH • LessOCeCl eq. of 1RRC COEt H 2 Cl Cl 1 Cl :TePhCl R C R1 :TePh R C R Br C C Hbromoacetate2CC and O O OEt OOEt O H Ce sodium tellurideR 1RHC CH CO Et R1RHC CH CO PhTeLiEt 1 Cl 2Cl 2 PhTeLi :TePhPhTeBr2 2 PhTeTePhR C R OH PhTeBr PhTeTePh OH O R1RHC CH CO Et 4.2.2 Knoevenagel-typePhTeLi reaction 2 2 4.2.2 Knoevenagel-typeFukuzawa, S.reaction I.; Irai, K. J. Chem. Soc. Perkin Trans. 1 1993PhTeBr, 1963. PhTeTePh OH Tellurium tetrachloride is an efficient catalyst in the Knoevenagel reaction of non-enoliz-12 Tellurium tetrachloride is an efficient catalyst in4.2.2 the Knoevenagelable Knoevenagel-type aldehydes reactionwith active of methylenereaction non-enoliz- compounds.5 5 able aldehydes with active methylene compounds. CN TeCl4 CN ArCHO + H C ArCH C Tellurium tetrachloride is an efficient2 Rcatalyst80°C, 20-75in the min KnoevenagelR reaction of non-enoliz- CN TeCl4 CN 5 (82-95%) ArCHO + H C able aldehydesArCH Cwith active methylene compounds. 2 R R 80°C, 20-75 min Ar = Ph and substituted Ph, 2-furyl, E -C6H5CH=CH (82-95%) R = CO2Et, CN,CN CONH2 TeCl4 CN ArCHO + H C ArCH C 2 R R Ar = Ph and substituted Ph, 2-furyl, ETypical-C6H5 procedureCH=CH .5 A mixture of the carbonyl80°C, 20-75 compound min (0.01 mol), the active methylene (82-95%) R = CO2Et, CN, CONH2 compound (0.01 mol) and tellurium(IV) tetrachloride (0.001 mol) was thoroughly mixed at room temperature.Ar = After Ph and being substituted stirred for Ph, 5 2-furyl,min, the E -CmixtureH CH=CH was heated and continu- Typical procedure.5 A mixture of the carbonyl compound (0.01 mol), the active methylene 6 5 ously stirred at 80°RC = in CO an2 Et,oil bathCN, CONH(20–752 min). The reaction was cooled at room temper- compound (0.01 mol) and tellurium(IV) tetrachlorideature (0.001 and mol) treated was with thoroughly a solution of mixed 1% aqueous alcohol. The product was extracted with Typical procedure.5 A mixture of the carbonyl compound (0.01 mol), the active methylene at room temperature. After being stirred for 5 min, themethylene mixture chloride, was heated washed and with continu- water. After drying over Na2SO4 the solvent was ously stirred at 80°C in an oil bath (20–75 min).compound The reactionremoved (0.01 inwas vaccuomol) cooled andover attellurium(IV) rotatory room temper-evaporator tetrachloride to obtain the (0.001 product mol) in high was purity. thoroughly mixed ature and treated with a solution of 1% aqueousat alcohol. room temperature. The product After was beingextracted stirred with for 5 min, the mixture was heated and continu- ously stirred at 80 C in an oil bath (20–75 min). The reaction was cooled at room temper- methylene chloride, washed with water. After drying over Na° 2SO4 the solvent was removed in vaccuo over rotatory evaporator to obtainature and the treatedproduct with in high a solution purity. of 1% aqueous alcohol. The product was extracted with methylene chloride, washed with water. After drying over Na2SO4 the solvent was removed in vaccuo over rotatory evaporator to obtain the product in high purity. Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 149

4.2 TELLURIUM-MEDIATED FORMATION OF ANIONIC SPECIES 149

β-chloroesters.

Cl i -Br2Te/TiCl4 CO2Et Br CO2Et + RCHO Ph CH2Cl2/ /(66%)

The described protocol was later improved by the use of the system PhTeLi/CeCl3.

PhTeLi (5.0 mmol)-CeCl (2.5 mmol) OH 1 3 1 EtO CCH Br + RR CO R RC CH2CO2Et 2 2 ether, 0°C - r.t., 1 h (47-95%) R = Ph; R1 = Me, Et 1 R = Me; R = C5H11 1 R, R = (CH2)5, O

R = R1 = PhCH2, i -pr

R, R1 =

The following scheme rationalizes the reaction.4

CeCl3 O OCeCl 1RRC COEt Else_TOS-PETRAGNANI_Ch004.qxdH 12/12/2006 6:51 PM2 Page 153 Br C C H2CC O O OEt OEt H Ce Cl Cl Else_TOS-PETRAGNANI_Ch004.qxd:TePh 12/12/2006 6:51R CPMR 1 Page 150 O R1RHC CH CO Et PhTeLi 2 2 PhTeBr PhTeTePh OH

REFERENCES 153 Formation4.2.2 Knoevenagel-type of anion reaction species and their reactions

Telluriumbenzyl tetrachloride chloride (0.632 iswith an g, efficient 5 mmol) electrophiles incatalyst THF (3 in mL) the isKnoevenagel added and the reaction mixture of kept non-enoliz- at 90°C for 5 h. After cooling the solvent is evaporated 5under reduced pressure and the residue • Knoevenagel-type150able aldehydes with active reaction methylene compounds. 4. TELLURIUM IN ORGANIC SYNTHESIS treated with aqueous NH4Cl and benzene. The organic phase is evaporated after filtration ® through Celite and worked up asCN usual toTeCl give4 benzyl p-tolyl sulphoneCN (0.179 g (75%); ArCHO + H C ArCH C 4.2.3m.p. Pinacol 143–145 reaction°C). 2 R 80°C, 20-75 min R activated (82-95%) methylene 10 Method B. To a solution of (EtO)2P(O)TeNa (5 mmol) in EtOH (10 mL) is added a Tellurium powder/KOHAr is= Phan andefficient substituted system Ph, 2-furyl,for the E pinacolization-C6H5CH=CH of aromaticis required carbonyl solution of benzeneR =sulphonyl CO Et, CN, chloride CONH (0.88 g, 5 mmol) in THF (10 mL) under N2. An compounds.instantaneous6 reaction occurs2 and the colour2 of the mixture changes from colourless to TypicalThe methoddeep procedure black. is advantageousAfter.5 Khan,A stirringmixture R. H.; Mathur, for of over 20the R. min, K.; carbonylothers Ghosh, a solution A.since C.compound Synth. itof isCommun.benzyl a very(0.01 chloride1996 fast mol),, 26, reaction.683. (0.64 the activeg, 5 mmol) methylene and catalytic amounts of BzEt NϩClϪ (0.01 g) in THF (10 mL) is added. The mixture is • Pinacolcompound reaction (0.01 mol) and tellurium(IV)3 tetrachloride (0.001 mol) was thoroughly mixed refluxed for 4 h. After evaporating the solvent under reduced pressure, the residue is at room temperature. After being stirredTe/KOH for 5 min, theH mixture was heated and continu- treated with CHCl (50ArCOR mL). After filtration,Ar(R) the organicC CH(R)Ar phase is evaporated to dryness. ously stirred at 80°C in3 an oil bathMeOH, (20–75 r.t. min). The reaction was cooled at room temper- The crude product is recrystallized from EtOH, givingOH theOH pure product (1.93 g (82.4%); ature and treated with a solution of10-15 1% minaqueous alcohol. The product was extracted with m.p. 145–147°C). (85-95%) • very fast reaction methylene chloride, washed with water. After drying over Na2SO4 the solvent was removed in vaccuo over rotatoryR = H; Ar evaporator = Ph and substitutedto obtain the Ph product in high purity. 4.2.6 Telluride-mediatedR = Me; Araldehyde = Ph, p-MeC methylenation6H4

TypicalIn procedure the presence.6 Benzaldehyde of Khan, dibutyl R. H.; Mathur,telluride, (0.53R. K.; iodomethyl Ghosh, g, 5 A. mmol) C. Synth. triphenylphosphonium Commun.was dissolved 1997, 27, 2193. in iodide methanol reacts (15with mL), • Wittig-typetelluriumaldehydes, powder reaction in (1.276 accordance g, 10 with mmol) a Wittig-type and KOH olefination, (1.40 g, giving 25 mmol)methylenation were products.added and11 the reaction mixture was stirred. The reaction became vigorous immediately after the addition n -Bu2Te + - + - of KOH. The reactionPh P I mixtureI was filteredPh P toI removeTeBu2-n theI tellurium powder[Ph3P=CH and2] water (50 3 THF, 80°C 3 -n-Bu2TeI2 mL) was added to the filtrate. A solid precipitated out which was filtered off under pres- R sure. Some of theRCHO diol was obtained by extracting the filtrate with CH2Cl2 (3×20 mL), dry- - + O R ing with anhydrous Na2PhSO3P4 and then-Ph3PO concentrated using a vacuum rotatory evaporator. (51-87%)

R = Ph, p -Cl, p -Br, p-FC6H4, PhCH=CH, 2-naphthyl, n -C9H19 4.2.4 Alkylidenation of aldehydes and cyclopropanation of -unsatu- Li, S. W.; Huang, Y. Z.; Shi, L. L. Chem.11 Ber. 1990, 123, 1441. α,β Methylenationrated carbonyl reaction compounds (typical procedure) with. Adibromomalonic mixture of iodomethyl esters triphenylphospho- 13 nium iodide (0.530 g, 1.0 mmol), dibutyl telluride (0.242 g, 1.0 mmol) and p-bromoben- zaldehyde (0.096 g, 0.5 mmol) in THF (5 mL) is heated under reflux for 30 h, then cooled Dibromomalonatesand filtered. The react residue with is aldehydes purified by underTLC, giving the assistance p-bromostyrene of dibutyl (0.080 telluride g (87%)). (2 equiv) to afford alkylidene malonates.7

REFERENCES H Br CO R1 H CO R1 2 Bu2Te (2 equiv) 2 1. Suzuki,R S.; OInouye,+ M. Chem. Lett.1 1986, 403. 1 Br CO2R r.t. (47-87%) R CO2R 2. Suzuki, H.; Manabe, H.; Inouye, M. Nippon Kagaku Kaishi 1987, 1485. 3. Suzuki,R H.;= Ph, Manabe, n-hexyl, H.; CHEnokiya,2=CH, R.; MeCH=CH, Hanazaki, Y. CH Chem.2=CMe, Lett. trans 1986,1339.-PhCH=CH 4. Fukuzawa,R1 = Me,S. I.; EtIrai, K. J. Chem. Soc. Perkin Trans. 1 1993, 1963. 5. Khan, R. H.; Mathur, R. K.; Ghosh, A. C. Synth. Commun. 1996, 26, 683. 6. Khan, R. H.; Mathur, R. K.; Ghosh, A. C. Synth. Commun. 1997, 27, 2193. Otherwise,7. Matsuki, dibromomalonates T.; Hu, N. X.; Aso, Y.; (and Otsubo, nitriles) T.; Ogura, react F. Bull. with Chem. α-unsaturated Soc. Jpn. 1989 , carbonyl62, 2105. compounds in8. the Padmanabhan, presence S.; of Ogawa, only 1T.; equiv Suzuki, of H. dibutyl Bull. Chem. telluride, Soc. Jpn. giving 1989, 62, cyclopropane 1358. derivates.

R Br Y Bu2Te R + CO2R Br Y r.t. (32-94%) CO2R

R = CO2Me, CO2Et, CO2Bu, COMe, CN; Y = CO2Me, CO2Et, CN

These reactions have been rationalized as involving the addition of an intermediate tellurium enolate to the carbonyl group or to the β-carbon, respectively, followed by a Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 150

150 4. TELLURIUM IN ORGANIC SYNTHESIS Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 150 4.2.3 Pinacol reaction

Tellurium powder/KOH is an efficient system for the pinacolization of aromatic carbonyl compounds.6 The method is advantageous over others since it is a very fast reaction. 150 4. TELLURIUM IN ORGANIC SYNTHESIS Te/KOH H ArCOR Ar(R) C CH(R)Ar MeOH, r.t. OH OH 4.2.3 Pinacol reaction 10-15 min (85-95%) R = H; Ar = Ph and substituted Ph Tellurium powder/KOH is an efficient system for the pinacolization of aromatic carbonylR = Me; Ar = Ph, p-MeC6H4 compounds.6 6 The method is advantageous over others since it is a veryTypical fast reaction. procedure. Benzaldehyde (0.53 g, 5 mmol) was dissolved in methanol (15 mL), tellurium powder (1.276 g, 10 mmol) and KOH (1.40 g, 25 mmol) were added and the reaction mixture was stirred. The reaction became vigorous immediately after the addition Te/KOH H ArCOR Ar(R) C CH(R)Ar MeOH, r.t. of KOH. The reaction mixture was filtered to remove the tellurium powder and water (50 OH OHmL) was added to the filtrate. A solid precipitated out which was filtered off under pres- 10-15 min (85-95%) sure. Some of the diol was obtained by extracting the filtrate with CH2Cl2 (3×20 mL), dry- R = H; Ar = Ph and substituted Ph ing with anhydrous Na2SO4 and then concentrated using a vacuum rotatory evaporator. R = Me; Ar = Ph, p-MeC6H4

6 Typical procedure. Benzaldehyde (0.53 g, 5 mmol) was 4.2.4dissolved Alkylidenation in methanol (15 of mL), aldehydes and cyclopropanation of α,β -unsatu- tellurium powder (1.276 g, 10 mmol) and KOH (1.40 g, 25 mmol)rated were carbonyl added andcompounds the with dibromomalonic esters reaction mixture was stirred. The reaction became vigorous immediately after the addition of KOH. The reaction mixture was filtered to remove theDibromomalonates tellurium powder and react water with (50aldehydes under the assistance of dibutyl telluride (2 equiv) mL) was added to the filtrate. A solid precipitated out whichto afford was alkylidenefiltered off malonates. under pres-7 sure. Some of the diol was obtained by extracting the filtrate with CH2Cl2 (3×20 mL), drying with anhydrous Na2SO4 and then concentrated using a vacuum rotatoryH evaporator. 1 1 Br CO2R Bu Te (2 equiv) H CO2R + 2 R O Br 1 1 Formation of anion species andCO2R theirr.t. (47-87%) reactionsR CO2R 4.2.4 Alkylidenation of aldehydes and cyclopropanation of α,β -unsatu- R = Ph, n-hexyl, CH2=CH, MeCH=CH, CH2=CMe, trans -PhCH=CH rated carbonyl compounds with dibromomalonicwith electrophiles estersR1 = Me, Et • AlkylidenationElse_TOS-PETRAGNANI_Ch004.qxd of aldehydes and 12/12/2006 cyclopropanation 6:51 PM Page of α151,β -unsaturated carbonyl Dibromomalonatescompounds react with aldehydes with dibromomalonic under the assistance Otherwise,esters of dibutyl dibromomalonatestelluride (2 equiv) (and nitriles) react with α-unsaturated carbonyl com- to afford alkylidene malonates.7 pounds in the presence of only 1 equiv of dibutyl telluride, giving cyclopropane derivates.

H 1 1 R Br CO2R Bu Te (2 equiv) H CO2R Br Y Bu Te 2 + 2 CO R R O + 1 1 R 2 Br CO2R r.t. (47-87%) R CO2R Br Y r.t. (32-94%) CO2R

R = Ph, n-hexyl, CH4.22=CH, TELLURIUM-MEDIATED MeCH=CH, CH2=CMe, trans FORMATION-PhCH=CH OF ANIONIC SPECIES 151 R = CO2Me, CO2Et, CO2Bu, COMe, CN; R1 = Me, Et Y = CO2Me, CO2Et, CN telluride-assisted elimination step or by an intramolecular cyclopropanation. Otherwise, dibromomalonates (and nitriles) react with Theseα-unsaturated reactions carbonyl have been com- rationalized as involving the addition of an intermediate pounds in the presence of only 1 equiv of dibutyl telluride,tellurium giving cyclopropane enolate to the derivates. carbonyl group or to the β-carbon, respectively, followed by a Br 1 Bu2TeO 1 R CO2R 1 Br CO2R + _ RCHO CO2R BuBr2Te Y+ Bu2Te Bu2Te Br Br + 1 CO R 1 1 R Br CO R 2 CO R R CO2R Br Y r.t. (32-94%)2 2 Br CO2R TeBu2 R = CO Me, CO Et, CO Bu, COMe, CN; - + 2 2 2 Bu2Te(Br)O + Bu2Te Br 1 R CO2R Y = CO2Me, CO2Et, CNR 1 H CO2R R 1 OH These reactions have been rationalizedR asCO involving2R the addition of an intermediateH2O _ 1 CO R + Bu TeBr Bu2Te tellurium enolate to the carbonyl group or to CO the2 Rβ-carbon, respectively,2 2 followed2 by a Br Br CO2R

Alkylidenation of aldehydes with dibromomalonates (typical procedure).7 A mixture of diethyl dibromomalonate (0.48 g, 1.5 mmol) and acrylaldehyde (0.087 g, 1.5 mmol) is treated with dibutyl telluride (0.73 g, 3 mmol) under argon and with stirring. After 30 min the mixtureMatsuki, is extracted T.; Hu, N. withX.; Aso, CHCl Y.; Otsubo,3 (30 T.; mL),Ogura, F. washed Bull. Chem. with Soc. H Jpn.2O, 1989 dried, 62, (MgSO2105. 4) and con- 14 centrated in vacuo. The residue is diluted in hexane (20 mL), insoluble material is filtered

off and the filtrate chromatographed on an SiO2 column (88–125 mesh, elution with CHCl3), giving dibutyltellurium dibromide (0.03 g (5%)) and then diethyl 2-propenyli- denemalonate (0.26 g (87%)), which is purified by Kügelrohr distillation (b.p. 65°C/0.12 torr).

Cyclopropanation of α,β-unsaturated carbonyl compounds with dibromomalonates (typical procedure).7 To a mixture of diethyl dibromomalonate (0.95 g, 3 mmol) and methyl vinyl ketone (0.27 g, 3.1 mmol) is added dibutyl telluride (0.73 g, 3 mmol) under argon and with stirring. The exothermic reaction is completed within 1 h. The mixture is

chromatographed on an Al2O3,column (70–230 mesh,elution with EtOAc), giving dibutyltellurium dibromide (1.01 g, 84%) and then 1-acetyl-2,2-bis(ethoxycar- bonyl)cyclopropane, which is purified by Kügelrohr distillation (0.59 g (86%); b.p. 88–90°C/0.08 torr).

4.2.5 Telluride-assisted sulphenylation and sulphonylation reactions

α-Phenylthiocarbonyl compounds and alkyl aryl sulphones are of great synthetic importance.8–10 New methods for their preparation are therefore the object of great interest. These two classes of compounds can be prepared by treating diphenyl disulphide8 and aryl sulphonyl chlorides9 with sodium telluride followed, respectively, by α-halocarbonyl compounds and alkyl halides. These methods involve the polarity reversal of the formerly electrophilic thio reagents, giving the thiolate and sulphinate anions through an electron transfer from the Organotellurium-based ring closure reactions

• General expression of ring closure reactions

• Tellurolactonization of unsaturated carboxylic acids • With aryltellurium trichlorides

Moura Campos, M.; Petragnani, N. Chem. Ber. 1960, 93, 317. ; Comasseto, J. V.; Petragnani, N. Synth. Commun. 1983, 13, 889

15 Organotellurium-based ring closure reactions

• Tellurolactonization of unsaturated carboxylic acids • With aryltellurium trichlorides

Without clear explanation

Moraes, D. N.; Santos, R. A.; Comasseto, J. V. J. Braz. Chem. Soc. 1998, 9, 397. H Ph Cl Ph O Ph O Ph

O TeAr O Cl Cl 16 Organotellurium-based ring closure reactions

• Tellurolactonization of unsaturated carboxylic acids • With benzenetellurenyl nitrobenzenesulphonate

Yoshida, M.; Suzuki, T.; Kamigata, N. J. Org. Chem. 1992, 57, 383. • With diaryl tellurium dihalides

Leonard, K. A.; Zhou, F.; Detty, M. R. Organometallics 1996, 15, 4285. • With phenyltellurenyl chloride

Xu, Q.; Huang, X.; Yuan, J. J. Org. Chem. 2005, 70, 6948. 17 Organotellurium-based ring closure reactions

• Reductive detelluration of tellurolactones

constitutes tributyltin hydride (TBTH)

TBTH: tributyltin hydride

Sn H

a formal protective method for γ,δ - unsaturated acids

Comasseto, J. V.; Ferraz, H. M. C.; Brandt, C. A.; Gaeta, K. K. Tetrahedron Lett. 1989, 30, 1209.; Comasseto, J. V.; Petragnani, N. Synth. Commun. 1983, 13, 889.

18 Organotellurium-based ring closure reactions

• Cyclotelluroetherification of unsaturated alcohols and allylphenols • With aryltellurinyl acetates

hygroscopicity and intractable nature

Some structures are problematic

• Moderate yield. • Small amount of 7-membered ring product Hu, N. X.; Aso, Y.; Otsuba, T.; Ogura, F. Tetrahedron Lett. 1987, 28, 1281.; Hu, N. X.; Aso, Y.; Otsuba, T.; Ogura, F. J. Org. Chem. 1989, 54, 4391.; Hu, N. X.; Aso, Y.; Otsuba, T.; Ogura, F. Phosphorus Sulfur 1988, 38, 177.

In accordance with the Baldwin rules

19 Organotellurium-based ring closure reactions

• With aryltellurium trichlorides the advantages of stability and easy separability of the formed crystalline dichlorotelluro derivatives compared to the preceding tellurinyl acetate method

The yields and the reaction times are close to those observed for the cyclization of the corresponding alcohols. The stereochemistry of the reaction is low

thiourea dioxide

Advantages: • Similar yield • stable • Less stereoselectivity • easy to separate

O TUDO: thiourea dioxide S NH O 2

NH2

Comasseto, J. V.; Ferraz, H. M. C.; Petragnani, N.; Brandt, C. A. Tetrahedron Lett. 1987, 28, 5611.; Comasseto, J. V. Grazini, M. V. A. Synth. Commun. 1992, 22, 949. Comasseto, J. V.; Ferraz, H. M. C.; Brandt, C. A.; Gaeta, K. K. Tetrahedron Lett. 1989, 30, 1209. 20 Organotellurium-based ring closure reactions • With benzenetellurenyl nitrobenzenesulphonate

hygroscopicity and intractable nature

Some structures are problematic

Yoshida, M.; Suzuki, T.; Kamigata, N. J. Org. Chem. 1992, 57, 383.

• With TeO2/HOAc/LiCl or TeO 2/HCl

Bergman, J.; Engman, L. J. Am. Chem. Soc. 1981, 103, 5196.; Engman, L. Organometallics 1989, 8, 1997. 21 Organotellurium-based ring closure reactions • With diaryl tellurium dihalides

hygroscopicity and intractable nature

Some structures are problematic

Leonard, K. A.; Zhou, F.; Detty, M. R. Organometallics 1996, 15, 4285.

• Synthetic applications

Comasseto, J. V.; Ferraz, H. M. C.; Brandt, C. A.; Gaeta, K. K. Tetrahedron Lett. 1989, 30, 1209.;Hu, N. X.; Aso, Y.; Otsuba, T.; Ogura, F. J. Org. Chem. 1989, 54, 4391 22 Organotellurium-based ring closure reactions

• Tellurocyclofunctionalization of alkenyl-substituted β-dicarbonyl compounds

• exo-mode • through enolate

Compare with Se: Much O higher yield and shorter Te reaction time CO2Et

Ferraz, M. H. C.; Comasseto, J. V.; Borba, E. B. Quim. Nova 1992, 15, 298.; Ferraz, M. H. C.; Sano, M. K.; Scalfo, A. C. Synlett 1999, 5, 567.; Stefani, H. A.; Petragnani, N.; Brandt, C. A.; Rando, D. G.; Valduga, C. J. Synth. Commun. 1999, 29, 3517. 23 Organotellurium-based ring closure reactions

• Tellurocyclization of olefinic carbamates

pyrrolidine and piperidine derivatives

Hu, N. X.; Aso, Y.; Otsuba, T.; Ogura, F. Chem. Lett. 1987, 1327. 24 Remove the Tellurium

• With formation of new C-C bonds

1 eq. of Bergman, J. Tetrahedron 1972, 28, 3323. Bergman, J. Org. Synth. 1977, 57, 18. metal

Bergman, J. Tetrahedron 1972, 28, 3323. Bergman, J. Org. Synth. 1977, 57, 18.

Bergman, J.; Engman, L. Tetrahedron 1980, 36, 1275.

Catalytic amount

Han, L. B.; Tanaka, M. Chem. Commun. 1998, 47. 25 Remove the Tellurium

• With formation of new C-C bonds

Coupling methods will be further discussed in application part

Kang, S. K.; Lee, S. W.; Ryu, H. C. Chem. Commun. 1999, 2117. Kang, S. K.; Hong, Y. T.; Kim, D. H.; Lee, S. W. J. Chem. Res. (S) 2001, 283.

Utilizing hypervalent iodonium salts

Kang, S. K.; Lee, S. W.; Kim, M. S.; Kwon, H. S. Synth. Commun. 2001, 31, 1721. 26 Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 199

4.6 CONVERSION OF ORGANOTELLURIUM COMPOUNDS 199

mixture was stirred for 5 h at 50°C, and then extracted. The reaction mixture was extracted with diethyl ether (3×20 mL). The organic layer was dried over anhydrous sodium sulphate and evaporated in vacuo. The crude product was separated by SiO2 column chromatography (EtOAc/hexanes, 1:30, Rf ϭ0.42) to afford 3-nitrobiphenyl (91 mg, 76%). 4.6.1.8 Palladium-catalysed cross-coupling of organotellurium compounds with hypervalent iodonium salts Diaryltellurium dichlorides can be readily coupled with iodonium salts in the presence of 13 palladium catalyst (PdCl2, 10 mol%) and MeONa in MeCN/MeOH.

PdCl (10 mol%), MeOH (3 equiv) + - 2 Ar2TeCl2 + RIPh ]X Ar-R MeCN/MeOH (1:1), r.t., 7 h (70-88%)

Ar = Ph, p -MeOC6H4 R = p -MeOC6H4, 2-thyenyl, (E )-PhCH=CH X = -OTs, -OTf, -BF4 Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 200 13 Typical procedure. To a stirred solution of Ph2TeCl2 (716 mg, 1.40 mmol), PdCl2 (25 mg, 0.14 mmol) and NaOMe (220 mg, 4.20 mmol) in CH3CN/MeOH (20 mL) under nitrogen atmosphere was added p-methoxyphenyl(phenyl)iodonium tetrafluoroborate (556 mg, 1.40 mmol) at room temperature. The reaction mixture was stirred at room temperature for 7 h. The reaction mixture was extracted with diethyl ether (3×20 mL). The organic layer was dried over anhydrous sodium sulphate and evaporated in vacuo. The crude product

200was separated by SiO2 column chromatography 4. TELLURIUM (hexane, IN ORGANICRf ϭ 0.17)SYNTHESIS to afford the coupled product (219 mg, 85%).

(p-MeOC64.6.1.9H4)2CO. The Detellurative alkaline extract carbonylation is acidified andof organotellurium extracted with ether. compounds: Evaporation preparation of of this ether extract gives p-MeOC H CO H (0.45 g (52%)). carboxylicRemove acids6 4 2 the Tellurium DetellurativeAryltellurium carbonylation trichlorides of diaryltellurium and diaryltellurium dichlorides dichlorides (typical react procedure) with nickel.14 tetracarbonyl

Following inthe DMF, above givingprocedure, benzoic Ni(CO) acids.4 (1.5 Small mL, amounts 11.5 mmol) of anddiaryl di- ptellurides-methoxyphenyl- and diaryl ketones are • With formation of new C-C bonds14 tellurium by-products dichloride (2.0 of these g, 4.8 reactions. mmol) furnish p-MeOC6H4CO2H (1.05 g (71%)), (p-MeOC H ) Te (0.25 g (15%)) and a trace amount of (p-MeOC H ) CO. 6 4 2 1) DMF, 70°C, 24 h 6 4 2 Carboxylic acidsArTeCl are3 also+ 2 producedNi(CO)4 through the detellurativeArCO carbonylationH + NiCl + NiTeof several + 7 CO + HCl 2) H O (52, 35%) 2 2 types of telluride by treatment with carbon2 monoxide at atmospheric pressure and room temperature in theAr presence = p -MeOC of6 HPd(II)4, 2-naphthyl salts, in various solvents.∗,15 These reactions are of particular interestsame since conditions the corresponding sulphur and selenium Ar TeCl + Ni(CO) 2 ArCO2H + NiTe + 2 CO + 2 HCl compounds give unsatisfactory2 2 results.4 (71, 58%)

Among the systemsAr = p-MeOC examined,6H4, Ph that of PdCl2/Et3N/MeOH provides the best results, furnishing the methyl esters directly. A black precipitate is formed during the reaction. Bergman, J.; Engman, L. J. Organomet. Chem. 1979, 175, 233. Detellurative carbonylation of aryltellurium trichloride: Ni(CO)4 method (typical proce- 14 dure). Ni(CO)4 (2.6CO(1 mL, atm)/PdCl 20 mmol)2 is added to p-methoxyphenyltellurium trichloride (2.0 g, RTeAr RCO2Me + ArCO2Me 5.9 mmol) in dry DMFEt N/MeOH (50 mL) under N . After 24 h at 70 C the excess Ni(CO) is evap- 3 A 2 B ° sulphur and 4 orated off in a stream of N . The mixture is then poured into H O (200 mL) containing 2 selenium2 48% HBr Ar(10 mL). The productR is extractedPercentage with etheryield (3×75 mL), and the ether solution extracted with 2 M NaOH. The ether solutionA containingB non-acidcompounds products give is dried Ph n -C12H25 22 98 unsatisfactory (CaCl2) and evaporated, giving (p-MeOC6H4)2Te (0.15 g, (15%)) and a trace amount of Ph Ph 92 results. p -MeOC H 6 4 p -MeOC6H4 99

These reactionsOhe, K.; can Takahashi, be performed H.; Uemura, catalytically S.; Sugita, N. in J. Org.PdCl Chem.2 if a 1987 suitable, 52, 4859. reoxidant such as CuCl2 is present.

Detellurative methoxycarbonylation of diorganyl tellurides. (a) PdCl2 stoichiometric Q2: Intermediates 15 method (general procedure). PdCl2 (0.177 g, 1.0 mmol) and the telluride (1.0 mmol) are and Products? flushed with CO from a CO balloon connected to the reaction flask at 25°C, to which dry MeOH (10 mL) and Et3N (0.202 g, 2.0 mmol) are added by a syringe. After stirring for 5 h at 25°C the black precipitate formed is filtered off, and the filtrate is poured into aqueous NH4Cl and extracted with ether (3×30 mL). The products are determined by GLC (using an EGSS-X 3% (1 m) column).

(b) PdCl2 catalytic procedure. PdCl2 (0.017 g, 0.1 mmol), CuCl2 (0.270 g, 2.0 mmol) and the telluride (1.0 mmol)Han, L. B.; are Kambe, flushed N.; withRyu, I.; CO Sonoda, from N. a Chem.CO balloon Lett. 1993 connected, 561. to the reaction 27

flask at 25°C, to which dry MeOH (10 mL) and Et3N (0.303 g, 3.0 mmol) are added by a syringe. After stirring for 75 h at 25°C, during which time the green colour turns dark brown, the brown solid is filtered off. The filtrate is poured into aqueous NH4Cl and extracted with ether (3×30 mL). The products are isolated by preparative TLC or Kügelrohr distillation, or determined by GLC (using an EGSS-X 3% (1 m) column with an appropriate inner standard).

*Similar reactions with vinyl tellurides will be discussed in Section 4.9.3.5. Remove the Tellurium

• With formation of other functionalities • By hydroxy group

An electrophilic mechanism is plausible for these reactions, on the basis of the depend- ence on para-electron- releasing groups and the enhancement by F− ions (forming ArTeCl3F22− or

Dabdoub, M. J.; Viana, L. H. Synth. Commun. 1992, 22, 1619. • By halogens

Retention of stereochemistry

Uemura, S.; Miyoshi, H.; Okano, M. Chem. Lett. 1979, 1357.

electrophilic mechanism is plausible

Hu, N. X.; Aso, Y.; Otsuba, T.; Ogura, F. Chem. Lett. 1987, 1327. 28 Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 209

4.6 CONVERSION OF ORGANOTELLURIUM COMPOUNDS 209 which also proceeds by using alkyl phenyl selenides, therefore contrasts sharply with the well-known selenoxide (and with the less familiar telluroxide) elimination leading to olefins. Improved yields are obtained by the similar treatment of telluroxides (prepared by hydrolysis of the parent dibromides)33 and different alcohols such as ethanol, propanol and isopropanol can be employed to give the corresponding ethers (method B). The detellurative methoxylation of the telluroxides also proceeds in high yields by treat- 32 ment with trifluoroperoxyacetic acid (generated in situ from TFA and H2O2) (method C). 34 Finally, alkyl phenyl tellurones (prepared by oxidation of telluroxides with NaIO4 are susceptible to similar conversions32 (method D).

(method A) MCPBA (3-5 equiv)/MeOH, r.t. RTePh ROMe (45-86%) Remove the Tellurium R=n -C12H25,PhCH2CH2, n -C12H25CHCH3, OMe • Withcycloheptyl, formation of otherElse_TOS-PETRAGNANI_Ch004.qxd functionalities 12/12/2006 6:51 PM Page 210 • By methoxy group 1 (1) Br2/CCl4 (method B) MCPBA (2 equiv)/R OH, r.t. 1 - RTe(O)Ph.H2O ROR (2) OH /H2O (65-95%) 1 R=n-C12H25;R =Me,Et,n-Pr, i-Pr 1 R=C8H17CH(OMe)CH2;R =Me NaIO4 MeOH/H2O (method C) F CCO H/H O /MeOH, r.t.210 4. TELLURIUM IN ORGANIC SYNTHESIS 3 2 2 2 ROMe (88%) R=n-C H 12 (2-hydroxy)cyclohexyl25 phenyl telluride (prepared by the opening of cyclohexenoxide with O (method D) MCPBA (2 equiv)/MeOH, r.t.the phenyltellurolate ion, see Section 3.1.3.2) are converted by the above-described proce- RTePh ROMe dure into the dimethyl acetals of the ring-contracted aldehydes, in contrast, therefore, to O (87%) R=n-C12Hthe25 detellurative methoxylation of the tetrahydronaphthalene derivative (see above). The difference in stability between the cyclic six- and seven-membered methoxy tel- In the above procedures, the telluroxide syn-elimination (see Section 4.7.1) was luroxides is noteworthy. Indeed, while the cyclohexane derivative is stable and isolable, observed as a competitive interference only in the case of cycloheptyl phenyl telluride, giving ring contraction on treatment with 1 equiv of MCPBA,Rearrangement the cycloheptane derivative where cycloheptene is formed in a yield of 45%. is unstable, suffering telluroxide elimination (like cycloheptenecould happen formation from cyclohep- When a phenyl group is linked at a vicinal position to tellurium, the tylreplacement phenyl telluride), of tel- as will be shown in Section 4.7. lurium by the methoxy group is accompanied by phenyl migration.31,32

MCPBA (2-5 equiv) OR OMe + MCPBA (1 equiv) O MeOH, r.t. H3O R R + MeOH, r.t. H3O () CHO TePh Ph Ph ()n TePh (77, 90%) ()n OMe n Ph MeO 1 R R1 (73-90%) R1 R =MeO n =1 R=Me,H 1 R = H; R =Me,MeO MCPBA (1equiv)/ 1 R=Me;R =MeO (1) Br2/CCl4 OR MeOH,r.t. - MCPBA (1 equiv)/ (2) HO /H2O n = 1 (84%) () (1) Br2/CCl4 R MeOH,r.t. n Te(O)Ph - Ph Te(O)Ph (2) HO /H O 1 (73-84%) 2 R OR MCPBA (1 equiv)/MeOH, r.t. OR 1 R=H,Me;R =OMe n =2 TePh -PhTeOH (2-Methoxy)cyclohexyl phenyl telluride and cycloheptyl phenyl telluride (easily acces- R = Me O (40%) sible by methoxy telluration of the corresponding cycloalkenes, see Section 4.4.8.3) and Uemura, S.; Fukuzawa, S. I. Tetrahedron Lett. 1983, 24,Detellurative 4347. Uemura, methoxylationS.; Fukuzawa, S. ofI. J. alkyl Chem. phenyl Soc. Perkin tellurides Trans. (typical1 1985, 471. procedure) .32 2-Methoxy

Detty, M. R. J. Org. Chem. 1980, 45, 274 3-phenyltelluro-1,2,3,4-tetrahydronaphthalene (1.85 g, 5 mmol) is treated with MCPBA 29 (3.3 g, 15 mmol) in MeOH (30 mL) at 25°C with stirring. After 1 h the mixture is treated with aqueous Na2S2O3 followed by aqueous NaHCO3 and extracted with ether (3×30 mL). The extract is dried (MgSO4) and evaporated, to leave a residue which is purified by SiO2 TLC (eluting with hexane/EtOAc, 4:1) to afford pure trans-2,3-dimethoxy-1,2,3,4-tetrahydronaphthalene (0.37 g, 1.94 mmol) and the cis-isomer (0.15 g, 1.76 mmol (54%)). Detellurative methoxylation of alkyl phenyl telluroxides (typical procedure).32 To a hetero- geneous solution of dodecyl phenyl telluroxide (0.82 g; 2 mmol) in MeOH (10 mL) is added solid MCPBA (80% purity, 0.88 g, 4 mmol) at 25°C with stirring. The resulting solution becomes homogeneous after 1 h, when it is treated with aqueous Na2S2O3 followed by aqueous NaHCO3. The mixture is treated with ether (3×30 mL), and the extract dried (MgSO4) and evaporated to leave a pale yellow oily residue which is purified by SiO2 column chromatography (eluting with hexane/EtOAc, 5:1) to afford pure dodecyl methyl ether (0.38 g (95%)).

(b) Correlate reaction – synthesis of α-arylpropanoic acids The title compounds, important anti-inflammatory pharmaceuticals, can be synthesized starting from aromatic ketones, as depicted in the accompanying scheme, involving the above-described detellurative methoxylation in the key step.35,36 In an analogous sequence using the corresponding selenides, the yield of the substitu- tion of the bromine for the phenylseleno group is higher. This result depends on the Vinylic tellurides • Vinylcuprates by copper–tellurium exchange • Conjugate addition of enones

R1 and the vinyl group should be different in migrative property

Comasseto, J. V.; Berriel, G. N. Synth. Commun. 1990, 20, 1681.; Tucci, F. C.; Chiefﬁ, A.; Comasseto, J. V. Tetrahedron Lett. 1992, 33, 5721. 30 Vinylic tellurides

• Further functionalization

Marino, J. P.; Simonelli, F.; Stengel, P. G.; Ferreira, J. T. B. J. Braz. Chem. Soc. 1998, 9, 345

Moorhoff, C. M.; Schneider, D. F. Tetrahedron 1998, 54, 3279; Lee, K.; Wiemer, D. F. Tetrahedron Lett. 1993, 34, 2433.

Moraes, D. N.; Barrientos-Astigarraga, R. E.; Castelani, P.; Comasseto, J. V. Tetrahedron 2000, 56, 3327.

Barrientos-Astigarraga, R. E.; Moraes, D. N.; Comasseto, J. V. Tetrahedron Lett. 1999, 40, 265. 31 Vinylic tellurides • Reaction with epoxides

Tucci, F. C.; Chiefﬁ, A.; Comasseto, J. V.; Marino, J. P. J. Org. Chem. 1996, 61, 4975.

1,4- & 1,2- openning of epoxides

32 Vinylic tellurides • Application in Total synthesis

Marino, J. P.; McClure, M. S.; Holub, D. P.; Comasseto, J. V.; Tucci, F. C. J. Am. Chem. Soc. 2002, 124, 1664.

• Reaction with bromoalkynes

(Z)-enynes & (Z)-enediynes

Araujo, M. A.; Comasseto, J. V. Synlett 1995, 1145. 33 Vinylic tellurides • Exchange with Zinc and Aluminum

Stabilization from phenyl, ester or SiMe3 is required

Terao, Y.; Kambe, N.; Sonoda, N. Tetrahedron Lett. 1996, 37, 4741. Dabdoub, M. J.; Dabdoub, V. M.; Marino, J. P. Tetrahedron Lett. 2000, 41, 433.

Stüdemann, T.; Gupta, V.; Engman, L.; Knochel, P. Tetrahedron Lett. 1997, 38, 1005. • trapping experiments shows no organometallic intermediates • Radical intermediate?

Terao, J.; Kambe, N.; Sonoda, N. Synlett 1996, 779. 34 Vinylic tellurides • Coupling reactions • Pd(II)-catalysed coupling of vinyl tellurides

Nishibayashi, Y.; Cho, C. S.; Ohe, K.; Uemura, S. J. Organomet. Chem. 1996, 526, 335.; Uemura, S.; Takahashi, H.; Ohe, K. J. Organomet. Chem. 1992, 423, 19.

Retention of stereochemistry

Nishibayashi, Y.; Cho, C. S.; Uemura, S. J. Organomet. Chem. 1996, 507, 197.

35 Vinylic tellurides

• Ni(II)- or Cu(I)-catalyzed cross-coupling with Grignard reagents

substrate control

Uemura, S.; Fukuzawa, S. I.; Patil, S. R. J. Organomet. Chem. 1983, 243, 9.

Double bond stereochemistry retention

Huang, X.; Zhao, C. Q. Synth. Commun. 1997, 27, 237.

36 Vinylic tellurides

• Ni(II)- or Pd(II)-catalyzed Sonogashira-type cross-coupling

enyne units Double bond important in several stereochemistry anti-tumour agents retention & anti-biotics.

Zeni, G.; Perin, G.; Cella, R.; Jacob, R. G.; Braga, A. L.; Silveira, C. C. Synlett 2002, 10, 1. Zeni, G.; Comasseto, J. V. Tetrahedron Lett. 1999, 40, 4619.

Zeni, G.; Menezes, P. H.; Moro, A. V.; Braga, A. L.; Silveira, C. C. Synlett 2001, 9, 1473. Silveira, C. C.; Braga, A. L.; Vieira, A. S.; Zeni, G. J. Org. Chem. 2003, 68, 662. Raminelli, C.; Prechtl, M. M. G.; Santos, L. S.; Eberlin, M. N.; Comasseto, J. V. Organometallics 2004, 23, 3990.

heteroaromatic tellurium dichlorides

Braga, A. L.; Lüdtke, D. S.; Vargas, F.; Donato, R. K.; Silveira, C. C.; Stefani, H. A., Zeni, G. Tetrahedron Lett. 2003, 44, 1779.. 37 Vinylic tellurides

• Pd/Cu-catalysed cross-coupling with organyl zinc reagents

Dabdoub, M. J.; Dabdoub, V. M.; Marino, J. P. Tetrahedron Lett. 2000, 41, 433. Dabdoub, M. J.; Dabdoub, V. M.; Marino. J. P. J. Org. Chem. 2000, 41, 437. 38 Vinylic tellurides • Palladium catalyzed detellurative carbonylation

Double bond stereochemistry retention

Oxidant can also be CuCl2 , CuCl/O2 , FeCl3 , Ce(IV) salts or benzoquinone; CuCl2 is most efficient.

Ohe, K.; Takahashi, H.; Uemura, S.; Sugita, N. J. Org. Chem. 1987, 52, 4859. 39 Free Radical Chemistry

• Telluride-ion-promoted coupling of allylic halides

Allylic radical

Clive, D. L. J.; Anderson, P. C.; Moss, N.; Singh, A. J. Org. Chem. 1982, 47, 1641.

40 Free Radical Chemistry • Organyl tellurides as exchangers of carbon radicals

Q3: Mechanism? Initiator: N- acetoxy-2- thiopyridone

Synthesis of antibiotic showdomycin

Barton, D. H. R.; Ramesh, M. J. Am. Chem. Soc. 1990, 112, 891. 41 Free Radical Chemistry

• Intramolecular radical cyclizations

SPy R

Barton, D. H. R.; Ramesh, M. J. Am. Chem. Soc. 1990, 112, 891.

Barton, D. H. R.; Gero, S. D.; Sire, B. Q.; Samadi, M.; Vincent, C. Tetrahedron 1991, 47, 9383.

42 Free Radical Chemistry • Telluroesters as source of acyl radicals

Telluroesters: excellent sources of acyl radicals [upon photolysis with a 250 W tungsten lamp, or thermal process (benzene at reflux) in the dark.]

Crich, D.; Chen, C.; Hwang, J. T; Yuan, H.; Papadatos, A.; Walter, R. I. J. Am. Chem. Soc. 1994, 116, 8937. 43 Free Radical Chemistry

Achieve 7,8- membered ring with strained substrate

The importance of conjugated olefin or aromatic ring

Crich, D.; Chen, C.; Hwang, J. T; Yuan, H.; Papadatos, A.; Walter, R. I. J. Am. Chem. Soc. 1994, 116, 8937. 44 Free Radical Chemistry • 2-Allyloxy alkyl tellurides as precursors of tetrahydrofuran derivatives

The control of DB configuration is not satisfying

Engman, L.; Gupta, V. J. Chem. Soc. Chem. Commun. 1995, 2515. Engman, L.; Gupta, V. J. Org. Chem. 1997, 62, 157. 45 Free Radical Chemistry

• Synthesis of indole derivatives via radical cyclization

important target in medicinal and agricultural chemistry

Ueda, Y.; Watanabe, H.; Uemura, J.; Uneyama, K. Tetrahedron Lett. 1993, 34, 7933. 46 Free Radical Chemistry • Organotellurium compounds as initiators for controlled living radical polymerization

Advantages: • Easy to synthesize a tailor-made initiator • Easy to modify the polymer end-group

diblock and triblock copolymer synthesis

ditelluride-capping mechanism

Yamago, S.; Lida, K.; Yoshida, J. I. J. Am. Chem. Soc. 2002, 124, 2874. Yamago, S.; Lida, K.; Yoshida, J. I. J. Am. Chem. Soc. 2002, 124, 13666. 47 Thanks for your attention! Q1 answers

Q1: For the following reactions, please give an explanation to the observed result that ether instead of alcohol is the main product in the existence of zinc iodide.

Nagakawa, K.; Osuka, M.; Sasaki, K.; Aso, Y.; Otsubo, T.; Ogura, F. Chem. Lett. 1987, 1331. 49 Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 201

Q2 answers 4.6 CONVERSION OF ORGANOTELLURIUM COMPOUNDS 201 Q2: From bis(oxoalkyl)tellurium dichlorides, we can synthesize enones and cyclopropanes. The mechanism involves the intermediacy of a bis-ylide4.6.1.10 which Synthesis further of enones reacts and cyclopropanes with aldehydes from bis(oxoalkyl)tellurium or enone. Please fill out the missing structures in Graph.1. dichlorides The sequential treatment of bis(2-oxomethyl)tellurium dichlorides with 2 equiv of LDA in THF at −78°C and 2 equiv of an aldehyde, followed by heating at 25°C, affords the enones with E geometry in good yields. The same reaction performed with methyl vinyl ketone gives rise to the cyclopropane.16 These reactions involve the intermediacy of a bis-ylide which undergoes a Wittig-type reaction with aldehydes or a Michael 1,4-addition to the enone.

O O O O Cl Cl LDA 2 equiv R R1CHO 2 equiv Te Te R R R R R1 THF, -78°C O THF, -78 -25°C 30 min O 3 h (42-89%)

R = Me, i -pr, i -Bu, t -Bu, Ph, p -MeOC H 6 4 2.5 equiv R1 = Ph, n-C H 8 17 O + R Te O Cl Cl O R R PhCHO (2 eq), THF O Te LDA (2 eq), THF O O o o o R = t -Bu 69% -78 C, 30 min -78 C~ 25 C, 3 h - MeO OMe O Moreover, if R is an aryl or t-butyl group, by warming at room temperature after the O treatment with LDA at −78°C, triacyl-substituted cyclopropanes are formed via a Michael addition involving the intermediates bis-ylide and bis-acylethylene.16

2.5 eq

O Cl Cl O LDA 2 equiv O O R Te Te R R R THF, -78°C R R O 30 min O

R = t -Bu, Ph, p -MeOC6H4, 1-adamanthyl, 1-MeC-prop O R

O O

RR (46-89%)

4.6.1.11 Conversion of telluroesters into ketones Han, L. B.; Kambe, N.; Ryu, I.; Sonoda, N.By Chem. treatment Lett. 1993with ,dialkylcuprates, 561. telluroesters are easily converted into ketones50 in high yields.17

R2CuLi/ether, -78°C RCOTePh ArCOR R = Me (1.1 equiv; 15 min, 87%) R = n -Bu (1.2 equiv; 30 min, 97%) Else_TOS-PETRAGNANI_Ch004.qxd 12/12/2006 6:51 PM Page 262

262 4. TELLURIUM IN ORGANIC SYNTHESIS

alkyl anisyl telluride, to afford methyl anisyl telluride and a new alkyl radical. In the presence of an electrophilic olefin, the alkyl radical is trapped, giving a relatively electrophilic radical, which in turn reacts with the thiocarbonyl function of the starting reagent to afford a tandem adduct, and reforming the methyl radical, thus beginning a new cycle.3,4

hυ . +CO2 +Me N S (W) N S. O Me O

AnTeR + Me. AnTeMe + R.

. X R + X R .

X R X N . R . S N S +Me + CO2 O Me O An = p -MeOC6H4

The radical chemistry discussed above is very useful for the manipulation or synthesis Else_TOS-PETRAGNANI_Ch004.qxdof complex products. 12/12/2006 6:51 PM Page 262 4.10.2.1 Tellurium-mediated addition of carbohydrates to olefins Carbohydrate anisyl tellurides areQ3 easily answersprepared by treatment of the corresponding mesy- lates or tosylates with the anisyl tellurolate anion. By irradiation of these tellurocarbohy- Q3: In the presentation, we have talked about the free radical chemistry of organyl tellurides. drates in the presence of N-acetoxythiopyridone and the electrophilic olefin, the tandem Reactions using N-acetoxy-2-thiopyridone as initiator have shown to be useful in the synthesisadduct of is antibiotics. formed. The Please oxidative draw elimination the mechanism of the thiopyridine for the following moiety leads reaction. to the trans- olefins.4 262 4. TELLURIUM IN ORGANIC SYNTHESIS

alkyl anisyl telluride,AcO to afford methyl anisylN tellurideS and aO new alkyl radical. In the pres- O OAc H ence of an electrophilic olefin,TeAn the+ alkylR radical is trapped, giving a relativelyN electrophilic CH Cl , 5 C, AcO 2 2 ° OAc S radical, whichAcO in turnOAc reactsH with the thiocarbonylhυ,10min function of the starting reagent to afford . R 3,4 a tandem adduct, and reforming the methyl(-Me radical,, -CO2) thus beginning a new cycle. O N O (86%) R = SO2Ph, (76-82%) MCPBA Me hυ . CO2+COMe, 2 +Me N sameS procedure(W) N S.COPh O Me AcO AcO O O O H H AcO AcO AcO OAc AcO OAc . . AnTeRO +N MeO AnTeMe + R R Me . X R + X R .

X R X N . R . S N S +Me + CO2 O Me O An = p -MeOC6H4 Barton, D. H. R.; Ramesh, M. J. Am. Chem. Soc. 1990, 112, 891. 51 The radical chemistry discussed above is very useful for the manipulation or synthesis of complex products.

4.10.2.1 Tellurium-mediated addition of carbohydrates to olefins Carbohydrate anisyl tellurides are easily prepared by treatment of the corresponding mesy- lates or tosylates with the anisyl tellurolate anion. By irradiation of these tellurocarbohy- drates in the presence of N-acetoxythiopyridone and the electrophilic olefin, the tandem adduct is formed. The oxidative elimination of the thiopyridine moiety leads to the trans- olefins.4

AcO N S O O OAc H TeAn + R N CH Cl , 5 C, AcO 2 2 ° OAc S AcO OAcH hυ,10min . R (-Me , -CO2) O N O (86%) R = SO2Ph, (76-82%) MCPBA Me CO2Me, same procedure COPh AcO AcO O O H H AcO AcO AcO OAc AcO OAc O N O R Me