2
R.M. APPA ET AL.
mechanism and large scope for the invention of potential synthetic methods are the
inborn futures of ultrasound-assisted synthesis.
The chiral tert-butanesulfinylimines developed by Ellman et al. become prevailed sub-
strates in organic synthesis. These are proved as effective auxiliaries in several reports
for making chiral amine-containing precursors and biologically significant complex mol-
ecules.[3] Moreover, (S)- and (R)-tert-butanesulfinamides and (S)- and (R)-a-methylben-
zylamines are widely accepted chiral ammonia equivalents among all the chiral amine
substrates.[4] In the beginning, Ellman et al. synthesized tert-butanesulfinimines by
MgSO4 catalyzed condensation of chiral tert-butanesulfinamides with aldehydes.[5] In
addition to the condensation of sulfinamides with carbonyl compounds, oxidative con-
densation of alcohols, thiols, ethers, sulfides and disulfides with tert-butanesulfina-
mides[6] are the other and less widely used approach for the construction of chiral tert-
butanesulfinimines. But, due to the wide scope of catalysts and substrates, the condensa-
tion of aldehydes with sulfinamides is a simple and routine practice to access these imi-
nes.[6b] In this connection, CuSO4,[7] Ti(OEt)4,[7,8] Cs2CO3,[9] KHSO4,[10] Yb(OTf)3,[11]
NaOH/tBuOK,[12] BnZnBr,[13] Amberlist-15,[14] pyrrolidine-4Å MS,[15] TiCl4,[16]
[21]
B(OCH2CF3)3,[17] B(OiPr)3,[18] TPA,[19] HBF4ꢀDEE[20] and I2
were also developed as
catalysts in addition to MgSO4. Nevertheless, these methods required toxic and expen-
sive organic solvent as media and many of these require a large quantity of catalysts (up
to 3 mol ratios). Hence, it is highly inevitable to develop mild and convenient protocols
for the synthesis of tert-butanesulfinimines.
Solid acid catalysts especially those based on silica support are widely used in organic
synthesis and have substantial benefits like easy preparation from inexpensive materials,
simple separation of the catalyst after the completion of the reaction by filtration, the pos-
sibility of recyclability and high substrate selectivity.[22] In the green chemistry point-of-
view, the synthetic process may be green when no (toxic) solvent is employed.[23] The
ecological pollution may be decreased by the application of solvent-free conditions in syn-
thesis since about 85% of the chemicals used in pharmaceutical industry are solvents and
their recovery rate is hardly about 50–80%.[24] Inspired by this ideology, we report herein
a convenient and effective method for the synthesis of chiral tert-butanesulfinyl aldimines
in the presence of silica supported p-tlouenesulfonic acid (pTSAꢀSiO2) as an efficient cata-
lyst under solvent-free and aerobic conditions. Furthermore, this is the first report to use
ultrasound for the synthesis of tert-butanesulfinimines under solvent-free conditions. For
the best of our knowledge, there are only a few reports exists for the use of pTSAꢀSiO2 as
a sole catalyst and all of them deals the dehydration of secondary and tertiary alcohols.[25]
This protocol further establishes the scope of the catalysis of pTSAꢀSiO2.
Results and discussion
Initially we have studied the imine formation reaction of benzaldehyde (1a) (1 mmol)
with (R)-tert-butanesulfinamide (2) (1.05 mmol) under ultrasound irradiation using
pTSAꢀSiO2 (100 mg, 1.6 mol%)[25] in 5 ml of THF, DCM or methanol and found 73%,
50% and 35% of (R)-tert-butanesulfinylimine (3a) in 1 h (Table 1, entries 1–3). No
improvement was observed by increasing catalyst load to 2.0 mol% (Table 1,
entries 4–6).