Скачиваний:
28
Добавлен:
15.08.2013
Размер:
997.62 Кб
Скачать

23. The thiocarbonyl group

1415

In situ combination of Lawesson reagent and anthracene allows reactive thioaldehydes to be formed and subsequently trapped as Diels-Alder cycloadducts, as illustrated in the case of pentafluorothiobenzaldehyde289 (equation 43), which is very reactive and polymerizes rapidly.

 

 

C6 F5

S

 

 

 

H

 

C6 F5

52/anthracene

 

 

 

 

 

O

 

 

(C6 F5CHS)n

 

 

H

benzene

 

 

(43)

Several groups have developed a range of modified Lawesson reagents, such as 56 introduced by Sandstrom¨ and coworkers290 and employed in the synthesis of twisted push pull ethylenes290,291. Reagent 56 is somewhat more stable than 52 and these authors recommend DME as the solvent of choice. The groups of Heimgartner292 and of Nicolaou293 have modified Yokoyama’s reagents (54, 55) by preparing analogs 57 59 which have been used primarily for the thionation of amides292 and lactones293. Finally, Davy has reported a number of bis(alkylthio) derivatives of 57 which have found wide application in the preparation of dithioesters294,295.

S

S

R P P R

S

S

(56) R = SCH3

S

S

R S P P S R

S

S

(57)R = CH3 2 9 2

(58)R = F 2 9 3

(59)R = Cl2 9 3

d.Other reagents. In addition to phosphorus sulfides, boron sulfides such as B2S3 have been used as mild sulfuration reagents. This reagent is generated in situ by treatment of

BCl3 with bis(tricyclohexyltin) sulfide296,297 and it has been applied to the thionation of nonenolizable diketones298. On the other hand, dimethylthioformamide was employed in the preparation of naphthothiopyranopyranthiones299 (equation 44).

Another reagent with limited application in thionation reactions has been S2Cl2, which afforded intermediates leading to 1,3,4-oxadithiolanes300. However, among the different thionating reagents developed in recent years the most successful has been bis(trimethylsilyl) sulfide, which in the presence of a catalyst affords thioaldehydes

1416 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

and thioketones under mild conditions. The selection of the catalyst is important

and CoCl2.6H2O for thioaldehydes301,302 and trimethylsilyl triflate for thioketones are preferred302,303 (equation 45).

 

CH3

 

 

 

 

CH3

 

O

 

S

 

 

 

O

 

 

H

N

Me

 

 

 

(44)

 

Me

 

 

S

 

 

 

 

 

O

 

 

 

 

 

S

 

 

 

 

 

S

 

 

O

 

 

 

S

 

 

R

R1

(Me

3 Si)2 S

R

R1

 

(45)

catalyst

 

 

 

 

 

 

R1 = H,SiMe3 , catalyst: CoCl2 . 6H2 O

R1 = alkyl, vinyl, catalyst:TfOSiMe3

As usual, thioaldehydes were trapped in situ as Diels-Alder adducts and the intramolecular version of this strategy using a catalytic amount of butyllithium has also been reported304.

2. Acetals

Dimethyl acetals have been treated with hydrogen sulfide in the presence of zinc chloride to afford tautomerically pure aliphatic thioketones 60 (equation 46)305.

 

MeO

 

 

S

 

SH

R1

OMe

H

S

R1

R1

 

 

 

2

 

R3

 

R3

 

R3

0.05 0.10 eq. ZnCl2

 

R2

R2

R2

 

H

 

 

 

 

 

 

H

 

 

 

R1 , R2 , R3 = alkyl

 

 

(60)

(61)

(46)

 

 

 

 

 

 

 

 

 

 

Enethiols 61 are tautomerically stable isomers of thioketones 60 and, in contrast to enols, enethiols have been isolated and characterized. This method provides a route for the selective synthesis of enethiols by deprotonation of 60 and quenching with trimethylchlorosilane, since under these conditions no isomerization takes place.

3. Imino derivatives

This approach is illustrated by the reaction of several immonium salts, obtained by Vilsmeier reaction with sodium hydrogen sulfide (equation 47) to afford a series of stable enamino thioaldehydes306.

R

CO2 Me

 

R

CO2 Me

 

R

CO2 Me

 

 

POCl3

 

 

NaHS

 

 

NH2

H

DMF

+

 

NH2

CHS

 

NH2

CH NMe2

 

 

 

 

 

 

 

 

(47)

23. The thiocarbonyl group

1417

S

 

Me2 N

S

N N

 

(62)

(63)

Other examples include the preparation of pyrazolinethiones307 62 and cyclopropenethiones308 63.

4. Halogen exchange

Optically active ˛-alkoxycarbonylthioaldehydes were prepared from the corresponding ˛-dichloroacetates by treatment with bis(tributyltin)sulfide and tetrabutylammonium fluoride309; 8-arylmenthols were used as chiral auxiliaries and the thioaldehydes underwent asymmetric hetero-Diels-Alder cycloaddition (equation 48).

 

 

 

S

 

 

 

(Bu3 Sn)2 S

R1O

 

 

S

Cl2 CHCO2 R1

TBA F

 

 

THF

 

H

 

 

 

 

 

 

 

 

 

 

 

 

 

O

 

 

 

 

 

 

CO2 R1

R1 = 8-arylmenthyl

 

+

 

 

 

 

 

 

 

 

 

 

CO2 R1

 

 

 

 

S

(48)

D. Addition Reactions to Alkynes and Alkenes

The addition of lithium hydrosulfide to acetylene affords enethiol systems310 and the addition of elemental sulfur to diethylaminoacetylenes yields ˛-dithiocarbonyl compounds311,312 (equation 49).

PhS

 

 

 

NEt2

S8

 

 

 

 

 

 

PhCl

 

 

 

 

 

 

 

 

PhS S

(49)

S NEt2

Two reactions which involve addition of sulfur reagents to alkenes have been reported for the first time. In the first, a mercapto[15]annulenone can be prepared from an annulenone by heating with sodium sulfide and elemental sulfur313 (equation 50). In the second, addition of sulfur to cyclic cumulenes gave rise to a series of interesting cyclizations, the

1418 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

final products being the tricyclic thiones in 22 27% yield314 (equation 51).

 

 

 

 

S

 

 

 

 

H

O

 

 

O

O

 

O

Na2 S

 

(50)

 

S8

 

 

 

O

 

O

 

 

 

Ar

 

Ar

Ar

S

 

 

 

 

Ar

 

 

S8

/ DBU

(51)

 

 

 

DMF

 

 

 

 

Ar

Ar

Ar

Ar

DBU = 1,8-Diazabicyclo[5.4.0]undec-7-ene

E. Elimination Reactions

1. C,C cleavage

The reaction of thiiranes with BF3ž Et2O results in the formation of cyclopentenethiones, by a new type of cyclization via the initially generated thioallyl cations315,316 (equation 52).

S

 

 

 

 

BF3

 

Ph

 

S

 

BF3 .Et2 O

 

 

 

 

 

Ph

 

Ph

 

 

+

TMS

 

 

 

TMS

Ph

 

 

 

(52)

S

TMS Ph

Ph

Photodissociation of thiophene yields several products among them thioketene, CH2DCDS, produced by C,C cleavage317. More synthetic utility possesses the thiocyanohydrins which, by vacuum-gas phase dehydrocyanation, yield the corresponding reactive thioaldehydes318 (equation 53). These thiocyanohydrins can be monoand

23. The thiocarbonyl group

dialkylated and also have been applied to the synthesis of thioketones319.

H

NC

 

CH

 

Cl

A qNaSH

NC-CH-SH

Gas-phase

 

 

 

 

dehydrocyanation

R

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

R

 

 

 

R

 

 

 

 

 

 

 

 

 

 

2. C,S cleavage

1419

S + HCN

(53)

Cleavage of a C S bond to give a thiocarbonyl derivative can be induced thermally, photochemically or by appropriate reagents1. Thermolysis has been carried out for mechanistic studies rather than for synthetic purposes and has been applied to the preparation of propynethial starting from propargyl sulfide in a flow system320 (equation 54).

 

 

 

 

 

 

 

 

 

 

 

 

T

S

HC

 

C

 

CH2

 

S CH2

 

C

 

CH

 

(54)

 

 

 

 

 

 

 

 

 

 

CH C C

 

 

 

 

 

H2 C

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

C

 

CH2

H

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Photolysis of a thiophene anhydride in an argon matrix at 12 K yielded a mixture of a thioketene and a thioaldehyde321 (equation 55).

 

O

 

 

 

 

 

 

hν

H

 

H

 

O

• • • S

+

• • • O

 

CO2

 

 

H

 

 

 

 

 

 

 

S

O

 

 

S

H

 

 

 

 

(55)

As mentioned earlier, flash vacuum thermolysis (FVT) is a very useful technique for the synthesis of reactive species20. It has been applied to the synthesis of thioketenes288 (equation 56), such as propadienethione, which were trapped by reaction with dimethylamine.

R1

SMe

 

R1

 

 

 

650 ° C

 

• S

(56)

 

 

−Μ eSSiMe

3

R2

 

R2

 

SSiMe3

 

 

Highly reactive thiocarbonyl derivatives have been prepared by photochemical Norrish- II-type cleavage of phenacyl sulfides 64 (equation 57). This mild and flexible route has been used by the group of Vedejs in key steps for the synthesis of natural products such as cytochalasans322 and macrolide antibiotics323. In the first case, a reactive thioaldehyde was generated by photolysis using the fragmentation of a phenacyl sulfide and the carbonyl compound was trapped in situ as Diels-Alder adduct in 66% yield322. On the other hand, a similar approach yielded a reactive thioketone which was trapped in a 1,3-dipolar cycloaddition323.

1420 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

 

O

 

R1

HO

Ph

H

CPh

 

 

 

hν

 

S +

 

 

 

C

(57)

R1R2 C

CH2

 

 

 

 

 

 

2

 

CH2

 

S

 

R

 

 

 

 

 

 

 

(64)

 

 

 

 

In addition to pyrolysis or photolysis, S,C cleavage may be induced by nucleophiles (or bases) in substrates with an electrophilic (or acidic) center and a leaving group next to the sulfur1. This is exemplified in the treatment of a bridged thiocyanate with potassium tert-butoxide leading to an ˛-oxo thioketone which spontaneously dimerizes (equation 58)324.

H

S

SCN t-BuOK

O O

(58)

dimerization

S

S

O

O

100%

Similarly, the S CN bond in thiocyanates can be cleaved affording the corresponding thiolate anions which may be protonated to enethiols325 (equation 59).

H

H

 

H

H

 

 

a. NaOH (15 min)

(59)

C

C

 

C C

 

 

 

b. HBF4

 

NCS

CO2 Me

 

HS

CO2 H

This approach has also been applied to heterocyclic systems such as thiazolidine- 2,5-dithiones, which by treatment with base in the presence of a nucleophile afford a number of pyrroline thiones326. Thiopyrilium salts also undergo ring cleavage to yield thiobenzophenones in low yield327. Applications to thioquinanthrene salts have also been reported328. Finally, it is interesting to note that a thioketone has been invoked as intermediate in the W(CO)6-mediated desulfurdimerization of dithioketals329 which represents an unprecedented type of fragmentation of the dithiolane moiety. This result can be explained considering that group 6 metal carbonyls are thiophilic and C S bond cleavage is thus favoured329 (equation 60).

23. The thiocarbonyl group

1421

S

S[W]

S

S

 

W(CO)6

 

 

(60)

S[W]

 

S

 

+ H2 C=CH2

Another new application has been the use of complexes such as Ni(acac)2 and Pd(acac)2, as catalysts in the fragmentation of dialkyl sulfoxides, which yielded reactive thials isolated by reaction with 1,3-dienes330 (equation 61).

O

RCH2 SCH2 RNi(acac)2

H2 O

R = Alkyl, Aryl

3. S,N cleavage

 

S

 

R C

+ RCH

 

CH2

(61)

 

 

 

H

 

The cleavage of the S N bond in a phthalimidesulfenyl derivative may be achieved with base yielding a thiocarbonyl compound, which is trapped either as [2 C 4] cycloaddition product331 or in a 1,3-dipolar reaction332 (equation 62).

O

 

 

 

 

+

 

CO2 R +

N

N S

BocNH

 

 

N

O

 

O

 

 

 

 

(62)

 

N

 

BocHN

S

 

N

 

 

 

O

CO2 R

 

 

 

R = Alkyl

N-Alkylisothiazolium salts undergo ring

cleavage when treated with complex

metal hydrides (NaBH4, LiAlH4) affording

high yields of ˇ-enaminothioketones333

1422 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

(equation 63). Many functional groups remain unchanged.

R

 

Me

 

 

 

 

 

NaBH4 or

 

 

N

 

 

 

 

 

LiA lH4

Me

 

+

Et

S

 

 

BF4

 

 

 

 

R = H, I, CN, NO2 , CO2 Et

R Me

Me

NHEt

(63)

S

8293%

The S,N cleavage can also be accomplished by matrix photolysis of several heterocycles which undergo extrusion of N2 and CO to afford heterocumulenes334 (equation 64), characterized by UV and IR spectra (see Section II).

 

O

 

 

 

 

 

 

 

 

 

 

 

 

 

 

N

S

 

 

 

 

 

 

 

 

 

 

 

 

 

 

N

 

N

hν

S

 

C

 

C

 

C

 

C

 

S

(64)

 

 

 

 

 

 

 

 

2N2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

S

N

 

2CO

 

 

 

 

 

 

 

 

 

 

 

 

O

An organometallic-based strategy for the cleavage of isoxazoles catalyzed by Co2(CO)8 has been reported by de Wang and Alper335.

4. S,Si cleavage

Ripoll and coworkers288 have reported the cleavage of silylated ketene dithioacetals under flash vacuum thermolysis (FVT) conditions20, which allowed the synthesis of propadienethione by combining this process along with the retro-Diels-Alder reaction (see Section III.F.5). Propadienethione was not isolated, but it underwent addition of the nucleophiles present in the reaction mixture288 (equation 65).

°

 

 

 

 

 

 

 

650 C

H2 C

 

C

 

C

 

S

 

 

 

 

anthracene

 

 

 

 

 

 

 

 

 

 

 

(65)

MeSSiMe3

 

 

 

 

 

SMe

SSiMe3

5. S,S cleavage

The cleavage of a S S bond has been extensively used for the preparation of thiocarbonyl compounds and this elimination can be induced thermally or by base

23. The thiocarbonyl group

1423

(E1cB mechanism)1. Thus, 9-thiofluorenone was prepared from the corresponding p- toluenethiosulfonate336 (equation 66).

A rSO2 SK

Br

H SSO2 Ar

A rSO2 H

(66)

S

Thioacylthioketenes are formed by FVT of various 1,2-dithiole or dithietane derivatives337,338 (equation 67) via a free radical mechanism.

S

S

S• S •

 

 

 

Ph

 

 

 

 

 

 

 

C C S

 

 

 

 

 

S

Ph

(67)

Ph

S

Ph

S

 

 

 

 

Ph

Ph

 

 

 

S

 

Another classical strategy involves the use of Bunte salts 65 to generate diethyl thioxomalonate339 (equation 68) or several transient thioaldehydes340, which undergo smooth cycloaddition with many dienes339, including the dienic system of thebaine340. In this case, transformation of the adducts gave rise to a variety of opiate agonists.

EtO2 C

CO2 Et + Na2 S2 O3

EtO2 C

CO2 Et

Et3 N

EtO2 C

CO2 Et

 

 

Cl

 

SSO3Na+

 

 

S

 

 

(65)

 

 

(68)

 

 

 

 

 

 

Disulfides treated with DABCO afforded thioketenes which were trapped with cyclopentadiene341 and photolysis of polysulfides produced a range of thione342 and dithione343 derivatives in low yields.

6. S,Se cleavage

An interesting reaction has been reported by Glass and coworkers344 consisting of the attack of a selenium heterocycle, Ebselen oxide 66, by ˛-toluenethiol (equation 69). In this reaction thiobenzaldehyde has been invoked as intermediate and could be trapped with cyclopentadiene. In the absence of a diene, dibenzyl disulfide is isolated instead of

1424 M. T. Molina, M. Ya´nez,˜ O. Mo,´ R. Notario and J.-L. M. Abboud

the thial along with selenenic acid 67.

O

 

 

 

 

 

 

 

 

 

N

 

Ph

CONHPh

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PhCH2 SH

 

 

 

Se

 

 

 

 

SeSCH2 Ph

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

O

O

 

 

PhCH2 SH

(69)

(66)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CONHPh

 

 

 

 

 

 

+

(PhCH2 S)2

SeOH

(67)

7. S,halogen cleavage

The elimination of HCl from the corresponding sulfenyl chlorides has been used in the synthesis of thioacetaldehyde182. The removal of HCl was accomplished by photolysis of ethanesulfenyl chloride in an argon matrix at 12 K (equation 70).

 

 

 

 

 

 

 

 

 

 

 

S

 

CH3

 

CH2

 

S

 

Cl

hν

CH3

 

C

+ HCl

(70)

 

 

 

366 nm

 

 

 

 

 

 

 

 

 

 

 

H

 

 

 

 

 

 

 

 

 

 

 

 

 

Related compounds such as alkanesulfonyl chlorides by treatment with base afford sulfene intermediates, which undergo attack by nucleophiles (H2O, alcohols, amines,

. . .) present in the reaction mixture. Although sulfenes have been the subject of intense studies345,346 it has been impossible so far to succeed in the isolation of even one of them.

Other labile thioaldehydes, such as EtO2CCHDS, have been prepared and trapped with anthracene347 (equation 71). On the other hand, a 1,6-elimination of HCl featured as key step in the generation of highly reactive monothioquinone S, S-dioxides 68 as depicted in equation 72348. the final products being the corresponding sulfonic acids.

 

H

EtOOCCH2SCl C Et3N ! [EtOOCCHDS]

(71)

 

 

 

 

 

 

 

 

 

 

 

Cl

O

 

 

 

 

O

 

 

 

 

OH

 

 

 

 

 

 

 

 

Cl

 

 

 

Cl

Cl

 

 

 

Cl

Cl

 

 

 

 

 

 

 

 

 

Base

 

 

 

 

H2 O

(72)

 

 

 

 

 

 

 

 

 

 

 

 

OSO

 

 

 

 

OSO

 

 

 

 

SO3

 

Cl

 

 

 

 

(68)

 

 

 

 

 

Соседние файлы в папке Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups