Table 1. [Rh((R,R)-R-sms-phos)(MeOH)2]BF4-Catalyzed Hydrogenation of S1-S7a
a The catalyst was prepared in situ from [Rh(nbd)2]BF4. Runs were carried out under 1 bar of H2 (10 bar for S7) at rt in MeOH (0.5 mmol of substrate
in 7.5 mL MeOH) with a S/C ) 100 (S/C ) 1000 for S1) for the time indicated (100% conversion) if not stated otherwise and are unoptimized. Typical
isolated yields were >90%. Ee’s were determined by chiral GC (prior to analysis the carboxylic group of hydrogenation product of S7 was esterified with
TMSCHN2). With (R,R)-R-SMS-Phos, S-configured products were obtained except with S6. b In the presence of Et3N (1.1 equiv). c 78% conversion. d 59%
conversion.
hydrogenation of an indicative set of olefinic reference
substrates S1-S7 (Table 1). Within the adopted systematic
bulkiness modification of the R groups, valuable changes in
reactivity and enantioselectivity of the Rh(I)-(R-SMS-Phos)
catalysts were noticeable. Operating with a S/C 100 in
methanol at rt under 1 bar of H2, methyl R-acetamidoacry-
late (S1: MAA) and cinnamate (S2: MAC) were hydro-
genated invariably with >99% ee’s within minutes.
However, the best hydrogenation results of methyl (Z)-
3-acetamidobut-2-enoate (S3: (Z)-MAB) and its (E)-isomer
(S4: (E)-MAB) were achieved with 3-Pen-SMS-Phos and
t-Bu-SMS-Phos furnishing 84.4% and 97.3% ee, respec-
tively. Further on, the hydrogenation of R-acetamidosty-
rene (S5: AS) and dimethyl itaconate (S6: DMI) also
proceeded smoothly within minutes with an incremental
increase in the ee, reaching, respectively, the maxima of
99.3% and 99.8% with t-Bu-SMS-Phos. Interestingly
enough, the bulkiest 3-Pen-SMS-Phos and t-Bu-SMS-Phos
designs afforded hydratropic acid from atropic acid (S7:
AA) with reasonably good ee’s, with up to 94.7% ee being
attained with t-Bu-SMS-Phos. Hydratropic acid constitutes
the basic model of nonsteroidal antiarthritics.6 Thus,
among the screened ligand set, the t-Bu-SMS-Phos ligand
emerged as being superior. Hence, the Rh(I)-(t-Bu-SMS-
Phos) catalyst was screened under mild hydrogenation
conditions against a selection of a broad diversity of
conventional, more challenging benchmark and new
classes of olefins S8-S19 (Table 2).
High reaction rates coupled with excellent ee’s were
reached in the hydrogenation of virtually all of the
considered various olefin groups.7 In particular, the
representative standard test substrate MAC (S2) was
hydrogenated (100% conversion) in 99.8% ee within 5.5 h
using a S/C 30000. ꢀ,ꢀ-Disubstituted dehydro-(N-acetyl)-
alaninates (S8 and S9) were hydrogenated equally well
under 3 bar of H2 in >99% ee within 2 h using a S/C
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(7) For indicative literature data regarding Rh-catalyzed hydrogenation
of these substrates with representative phosphines, see the Supporting
Information.
ˇ
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