O-p-Tolyl Chlorothioformate

[937-63-3]  · C8H7ClOS  · O-p-Tolyl Chlorothioformate  · (MW 186.67)

(synthesis of alkenes from hindered alcohols;1 deoxygenation of alcohols7)

Physical Data: bp 52-53 °C; d 1.21 g cm-3.

Solubility: sol most common organic solvents.

Form Supplied in: commercially available as liquid (97% pure).

Analysis of Reagent Purity: GC.

Handling, Storage, and Precautions: moisture sensitive; keep cold; corrosive; toxic; use in a fume hood.

Synthesis of Alkenes.

Formation of thiocarbonate O-esters from sterically hindered alcohols, followed by pyrolysis, provides an alternative to the Chugaev reaction in the synthesis of alkenes. In the examples shown in eqs 1 and 2, pyrolysis of the corresponding xanthates gives lower yields.1,2

The pyrolysis of thiocarbonate O-esters has been utilized in the synthesis of several natural products. In an approach to the synthesis of (-)-acorenone (eq 3), pyrolysis of the xanthate gives consistently low yields.3 The favored pathway appears to be conversion to the dithiol carbonate. Alternatively, conversion to the thiocarbonate O-ester and subsequent pyrolysis gives the desired alkene in 68% yield. This methodology has also been successfully used in a total synthesis of (±)-silphenene (eq 4).4 Ordinary dehydration conditions lead to retroaldolization, while pyrolysis of the thiocarbonate O-ester gives the desired enone in 84% yield. An intermediate in the total synthesis of (-)-hibaene has been prepared by pyrolysis of the respective monothiocarbonate O-esters of both epimeric diols (eq 5).5

Deoxygenation of Alcohols.

Thiocarbonate esters of alcohols can be deoxygenated using the Barton-McCombie procedure.6 Several examples of this deoxygenation methodology in the synthesis of deoxyribose nucleosides have been cited (eq 6).7-9

[Heteroaryl(hydroxy)methyl]phosphonates are readily converted to O,O-thiocarbonates on treatment with O-p-tolyl chlorothioformate in MeCN/DMAP, while the reaction in pyridine/CH2Cl2 affords the isomeric O,S-thiocarbonates (eq 7).10 Homolytic cleavage with Tri-n-butylstannane/Azobisisobutyronitrile provides a convenient approach to dialkyl heteroarylmethylphosphonates.

1. (a) Gerlach, H.; Huong, T. T.; Müller, W. CC 1972, 1215. (b) Gerlach, H.; Müller, W. HCA 1972, 55, 2277.
2. Paquette, L. A.; Larvik, P. B.; Summerville, R. H. JOC 1977, 42, 2659.
3. Lange, G. L.; Neidert, E. E.; Orrom, W. J.; Wallace, D. J. CJC 1978, 56, 1628.
4. Paquette, L. A.; Leone-Bay, A. JACS 1983, 105, 7352.
5. Duc, D. K. M.; Fetizon, M.; Lazare, S. T 1978, 34, 1207.
6. Barton, D. H. R.; McCombie, S. W. JCS(P1) 1975, 1574.
7. Agathocleous, D. C.; Shaw, G. JCS(P1) 1991, 2317.
8. Hiebl, J.; Zbiral, E.; Balzarini, J.; De Clercq, E. JMC 1992, 35, 3016.
9. Eschenhof, H; Strazewski, P.; Tamm, C. T 1992, 48, 6225.
10. Drescher, M.; &OOuml;hler, E.; Zbiral, E. S 1991, 362.

Judi A. McKinney

Tularik, South San Francisco, CA, USA

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