[851-06-9]  · C14H14N2O4S3  · Bis[N-(p-toluenesulfonyl)]sulfodiimide  · (MW 370.46)

(can act as an enophile in ene reactions4-6 and as a dienophile in Diels-Alder reactions;2,10-12 participates in [2 + 2]4 and [3 + 2]15,16 cycloaddition reactions; cycloadds to ynamines17)

Physical Data: bright yellow solid; mp 48-50 °C.

Solubility: sol benzene, toluene, chloroform, and methylene chloride.

Preparative Methods: a convenient in situ method for the synthesis of bis[N-(p-toluenesulfonyl)]sulfodiimide (1a) is by treating N-Sulfinyl-p-toluenesulfonamide with dry Pyridine in benzene (eq 1).2 An alternative procedure is the reaction of SCl2 or S2Cl2 with p-toluenesulfonamide in the presence of a base such as pyridine or triethylamine (eq 2).3

Handling, Storage, and Precautions: extremely sensitive to moisture and should be stored in a desiccator and handled only in a dry box or glove bag. Typically the title compound is generated and used in situ.

Ene Reaction or Allylic Amination.

Some years ago it was discovered that sulfur diimide (1a) is a highly reactive enophile, converting a wide variety of alkenes into sulfinamides under mild conditions. For example, (1a) reacts with allylbenzene at 10 °C to afford sulfinamide (3) in 91% yield (eq 3).4,5 This reactive intermediate spontaneously undergoes a [2,3]-sigmatropic rearrangement to produce the diaminosulfane (4). It was also shown that the N-S-N bond is readily cleaved using Na2SO3 to give the allylic sulfonamide (5) in excellent yield.5a

In a similar study, cyclic compounds, such as methylenecyclohexane, were shown to react with sulfur diimide (1a) to give principally disulfenamide (7) and initial ene product (6) as a minor component (eq 4).6 These sulfenamide intermediates are slowly hydrolyzed with K2CO3 to the corresponding allylic sulfonamides.

The allylic amination sequence has been applied to an elegant total synthesis of racemic gabaculine (11).7 Treatment of cyclohexenyl derivative (8) with (1a) followed by basic hydrolysis affords predominantly allylic sulfonamide (9) (eq 5).

In similar fashion, the allylic sulfonamide moiety was also introduced in a synthesis of N-tosyldaunosamine (12), a derivative of the carbohydrate daunosamine (eq 6).8

In a unique synthesis of functionalized 1,2,5-selenadiazole rings, homoallylic sulfonamide (13) was combined with (1a) to give bis(sulfonamide) (14) in 50% yield (eq 7).9 This sequence represents an extension of the methodology of Sharpless and Kresze to an alkenic substrate which already contains a sulfonamide group on the homoallylic carbon (see above).

Diels-Alder Reactions.

Sulfur diimide (1a) is a highly reactive dienophile in regioselective [4 + 2] cycloadditions of unsymmetrical dienes.1b,2,10 For instance, the Diels-Alder reaction of (1a) with (E)-piperylene (eq 8) and isoprene (eq 9) afforded C-3 and C-5 substituted 3,6-dihydrothiazin-1-imines, respectively, while chloroprene gave the 5-substituted cycloadduct (eq 10).11

As an application of this methodology, (E,E)-2,4-hexadiene and (1a) react in benzene to produce a separable mixture of 3,6-dihydrothiazin-1-imines (15a) and (16a) (91%) in a 1.1:1 ratio,12 while the cycloaddition with the bis(carbamate) (1b) afforded a 1:8 mixture of adducts (15b) and (16b), respectively (eq 11).13 This Diels-Alder strategy was also applied to isomeric (E,Z)-2,4-hexadiene. Reaction of this diene with (1a) gave a 1:7 mixture of cycloadducts (17a) and (18a) (75%), while addition of bis(carbamate) (1b) to (E,Z)-2,4-hexadiene yielded 2.4:1 mixture of adducts (17b) and (18b) (65%) (eq 12).

The 3,6-dihydrothiazin-1-imines generated from these hetero Diels-Alder processes were shown to be valuable intermediates in the stereocontrolled synthesis of unsaturated vicinal diamines.12 Refluxing cis-dihydrothiazine-1-imines (15) and (17) (in either the sulfur diimide series or the bis(carbamate) series) in benzene stereoselectively produced stable thiadiazolidines (19) and (21) (eqs 13 and 14), respectively, via a novel transannular [2,3]-sigmatropic process.13 Reduction of (19) and (21) with Sodium Borohydride gave (E)-threo vicinal diamine derivative (20) and (E)-erythro compound (22), respectively, in excellent yields.

In contrast, trans-dihydrothiazin-1-imines (16) and (18) (in both the sulfur diimide and bis(carbamate) series) reacted with Phenylmagnesium Bromide to give initial allylic sulfinimine products which underwent facile [2,3]-sigmatropic rearrangement through an envelope-like transition state to afford sulfenamides (23) and (24) (eqs 15 and 16), respectively.13 Desulfurization of sulfenamides (23) and (24) with Trimethyl Phosphite cleanly afforded the corresponding protected diamines in good yields.

The methodology for the stereoselective synthesis of unsaturated vicinal diamines was also applied in an attempted total synthesis of biotin (25).14 The Diels-Alder cycloaddition of (E,E)-diene (26) with (1b) occurred in high yield to produce a 7.7:1 mixture of epimeric 3,6-dihydrothiazin-1-imines (27) and (28) (eq 17). Heating adducts (27) and (28) in toluene induced the [2,3]-sigmatropic rearrangement, giving thiadiazolidines (29) and (30) in quantitative yield (eq 18). The mixture was readily separated and thiadiazolidine (29) was reduced, cyclized, and protected to afford urea (31) which unfortunately could not be converted to biotin.

Other Cycloaddition Reactions.

Sulfur diimide (1a) and vinyl ether (32) combine to afford an unstable [2 + 2] cycloadduct which spontaneously undergoes a [1,5]-hydrogen shift to produce substituted diaminosulfane (33) (eq 19).4

It has been shown that the periselectivity between ene reactions and [2 + 2] cycloadditions is delicately influenced by alkene geometry and stereoelectronic effects of the substituents.1a However, the periselectivity between a [2 + 2] and a [3 + 2] cycloaddition pathway was found to be dependent on the reaction temperature. For instance, if (1a) is added to diphenylketene at -15 °C, a reversible [2 + 2] cycloaddition takes place (eq 20), but at higher temperatures a [3 + 2] cycloaddition was observed (eq 21).15

Another illustration of a rare [3 + 2] cycloaddition of (1a) is the reaction with diphenylfulvene to give cycloadduct (34), albeit in only 30% yield (eq 22).16

Sulfur diimide (1a) also cycloadds to ynamines in a [2 + 2] process in a novel synthesis of 1,4-diaza-1,3-butadienes (eq 23).17


Sulfur diimide (1a) and the corresponding selenodiimide (see Bis[N-(p-toluenesulfonyl)]selenodiimide) have been utilized to synthesize N-tosylimines, but both procedures can occasionally suffer a lack of chemoselectivity since these reagents both also undergo Diels-Alder and ene reactions. Trost has developed an analogous procedure using tellurodiimide (36) (eq 24)18 which does not undergo these undesired side reactions. Tellurodiimide (36), generated from Tellurium metal and Chloramine-T, was combined with aldehyde (35) to afford N-tosylimine (38), presumably via a cycloaddition to a four-membered ring (37) followed by cycloreversion (eq 24).

Related Reagents.

Bis[N-(p-toluenesulfonyl)]selenodiimide; N-Sulfinyl-p-toluenesulfonamide.

1. (a) Bussas, R.; Kresze, G.; Muensterer, H.; Schwoebel, A. Sulfur Rep. 1983, 2, 215. (b) Boger, D. L.; Weinreb, S. M. In Hetero Diels-Alder Methodology in Organic Synthesis; Academic: Orlando, 1987; Chapter 1. (c) Zibarev, A. V.; Yakobson, G. G. RCR 1985, 54, 1706.
2. Wucherpfennig, W.; Kresze, G. TL 1966, 1671.
3. (a) Levchenko, E. S.; Bal'on, Ya. G.; Kirsanov, A. V. JOU 1967, 3, 2014. (b) Levchenko, E. S.; Bal'on, Ya. G.; Kirsanov, A. V. JOU 1967, 3, 2083.
4. Schönberger, N.; Kresze, G. LA 1975, 1725.
5. For a variety of examples see: (a) Bussas, R.; Kresze, G. LA 1980, 629. (b) Muensterer, H.; Kresze, G.; Lamm, V.; Gieren, A. JOC 1983, 48, 2833.
6. Sharpless, K. B.; Hori, T. JOC 1976, 41, 176.
7. Singer, S. P.; Sharpless, K. B. JOC 1978, 43, 1448.
8. Dyong, I.; Friege, H.; zuHöne, T. CB 1982, 115, 256.
9. Bertini, V.; Lucchesini, F. S 1979, 979.
10. Levchenko, E. S.; Balon, Y. G. JOU 1965, 1, 146, 295.
11. For earlier examples of the Diels-Alder cycloaddition of (1a) with the three isomeric 2,4-hexadienes, see: Mock, W. L.; Nugent, R. M. JACS 1975, 97, 6521.
12. Weinreb, S. M. ACR 1988, 21, 313.
13. Natsugari, H.; Whittle, R. R.; Weinreb, S. M. JACS 1984, 106, 7867.
14. (a) Turos, E.; Parvez, M.; Garigipati, R. S.; Weinreb, S. M. JOC 1988, 53, 1116. (b) For a similar example, see: Natsugari, H.; Turos, E.; Weinreb, S. M.; Cvetovich, R. J. H 1987, 25, 19.
15. Grill, H.; Kresze, G. TL 1970, 1427.
16. Saito, T.; Musashi, T.; Motoki, S. BCJ 1980, 53, 3377.
17. (a) Gotthardt, H.; Loehr, T.; Brauer, D. J. CB 1987, 120, 747. (b) Gotthardt, H.; Loehr, T.; Brauer, D. J. CB 1987, 120, 751.
18. Trost, B. M.; Marrs, C. JOC 1991, 56, 6468.

Steven M. Weinreb & Robert M. Borzilleri

The Pennsylvania State University, University Park, PA, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.