Methyl Phenylsulfonylacetate

[34097-60-4]  · C9H10O4S  · Methyl Phenylsulfonylacetate  · (MW 214.26)

(soft nucleophile which undergoes palladium(0)-catalyzed additions to allylic acetates, pivalates, tosylates, and epoxides; desulfonation affords aliphatic (4E)-enoates)

Alternate Name: (methoxycarbonyl)methyl phenyl sulfone.

Physical Data: bp 165 °C/0.05 mmHg; d 1.282 g cm-3.

Form Supplied in: liquid/oil; widely available.

Palladium(0)-Catalyzed Addition to Allylic Systems.

Methyl phenylsulfonylacetate has been used as a soft nucleophile in a variety of palladium(0)-catalyzed additions to allylic acetates, allylic pivalates, and allylic epoxides to afford alkyl 2-phenylsulfonyl (4E)-enoates. Addition to allylic acetates1,2 followed by desulfonation3 leads to the construction of trans-4-enoates (eq 1). Addition to allylic tosyl systems can be achieved, giving vinylcyclopropanes (eq 2).4

Cyclopentadiene monoepoxide can undergo palladium-catalyzed ring opening to give a palladium p-allyl complex which reacts with methyl phenylsulfonylacetate to afford cis-4-substituted 2-cyclopenten-1-ols5,6 after desulfonation using Sodium Amalgam (eq 3).7 The cyclopentenols can also be prepared in an optically active form starting from cis-4-acetoxy-1-hydroxy-2-cyclopentene.8

Methyl phenylsulfonylacetate can be alkylated using p-allyl complexes to afford alk-4-ene functionalities which can be treated with a palladium catalyst to form vinylcyclopropane ring systems. The phenylsulfonyl group can be removed by Na(Hg) reduction and the ester converted to aldehyde by reduction followed by oxidation to give a 60:40 mixture of cis- and trans-cyclopropanecarbaldehydes (eq 4).9

Alkylation with 5-bromo-1-pentene or 5-bromo-1-pentyne gives the alkenyl and alkynyl derivatives which can undergo palladium-catalyzed cyclization followed by a Heck reaction to give cyclopentanes or vinylidenecyclopentanes (eqs 5 and 6).10,11

The palladium cyclization reaction using the soft nucleophilic properties of the phenylsulfonylacetate system has been extended to the construction of macrocyclic ring systems.12,13 Methyl phenylsulfonylacetate can be deprotonated with Potassium t-Butoxide in t-butanol/DMSO and added, via Michael addition, to the unsaturated ketone. Macrocyclization is effected with Tetrakis(triphenylphosphine)palladium(0) and N,O-Bis(trimethylsilyl)acetamide in THF at reflux (eq 7).

Methyl phenylsulfonylacetate also undergoes a reductive addition to dienes in the presence of palladium(0) catalysts14 under basic conditions to give functionalized alkenes (eq 8).

1. Thompson, W. J.; Tucker, T. J.; Schwering, J. E.; Barnes, J. L. TL 1990, 31, 6819.
2. Cooper, J. A.; Cornwall, P.; Dell, C. P.; Knight, D. W. TL 1988, 29, 2107.
3. Brown, A. C.; Carpino, L. A. JOC 1985, 50, 1749.
4. Stolle, A.; Salaũn, J.; deMeijere, A. TL 1990, 31, 4593.
5. Trost, B. M.; Molander, G. A. JACS 1981, 103, 5969.
6. Deardorff, D. R.; Myles, D. C.; MacFerrin, K. D. TL 1985, 26, 5615.
7. Trost, B. M.; Arndt, H. C.; Strege, P. E.; Verhoeven, T. R. TL 1976, 17, 3477.
8. Deardorff, D. R.; Linde, R. G., II; Martin, A. M.; Shulman, M. J. JOC 1989, 54, 2759.
9. Colobert, F.; Genet, J.-P. TL 1985, 26, 2779.
10. Fournet, G.; Balme, G.; Gore, J. T 1990, 46, 7763.
11. Fournet, G.; Balme, G.; Gore, J. T 1991, 47, 6293.
12. Marshall, J. A.; Andrews, R. C. TL 1986, 27, 5197.
13. Marshall, J. A.; Andrews, R. C.; Lebioda, L. JOC 1987, 52, 2378.
14. Trost, B. M.; Zhi, L. TL 1992, 33, 1831.

Dinos Santafianos

Bristol-Myers Squibb Pharmaceutical Research, Princeton, NJ, USA

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