Efficient amide-directed catalytic asymmetric hydroboration

Article abstract of DOI:10.1021/ja710492q

A series of acyclic β,γ-unsaturated amides are shown to undergo highly regio- (>95%) and enantioselective (93-99% ee) rhodium-catalyzed hydroboration with pinacolborane (PinBH) using simple chiral monophosphite or phosphoramidite ligands in combination wi

Full text of DOI:10.1021/ja710492q

Published on Web 03/01/2008
Efficient Amide-Directed Catalytic Asymmetric Hydroboration
Sean M. Smith, Nathan C. Thacker, and James M. Takacs*
Department of Chemistry, UniVersity of Nebraska-Lincoln, Lincoln, Nebraska 68588-0304
Received November 20, 2007; E-mail: jtakacs1@unl.edu
Rhodium-catalyzed hydroboration has attracted much interest,
in part, because certain substrates react with complementary regio-
and diastereoselectivity as compared to the noncatalyzed reaction.1
The novel regiocontrol is exemplified by the rhodium-catalyzed
hydroboration of styrene which introduces boron at the benzylic
position yielding, after oxidation, predominately the R-aryl alcohol,
1-phenylethanol. The catalytic asymmetric variant of catalyzed
hydroboration is generally limited to the reactions of vinyl arenes.2
We recently reported that two simple TADDOL-derived phosphite
and phosphoramidite ligands afford high levels of enantioselectivity
(90-96% ee) in the rhodium-catalyzed asymmetric hydroborations
across a series of styrenes 1 (R ) OMe, CH3, H, CF3, Cl, F) (Figure
1).3,4 We now find that acyclic â,γ-unsaturated amides also undergo
regio- and enantioselective rhodium-catalyzed hydroboration with
pinacolborane (PinBH) using simple chiral monophosphite or
phosphoramidite ligands.
Figure 2. Highly enantioselective amide-directed catalytic asymmetric
hydroboration of â,γ-unsaturated amides (E)- and (Z)-1.
peroxide, intermediate 2 affords beta-hydroxy amide (S)-3 in good
yield and remarkably high enantiomeric purity (80% yield, 99%
ee).12
Many catalytic asymmetric reactions prove rather intolerant of
changes in the structure of the substrate. It is therefore interesting
to find that the diastereomeric (E)- and (Z)-isomers of 1 afford (S)-3
in the same yield and high enantiomeric purity. The reaction
proceeds with good regiocontrol regardless of the alkene geometry;
only 3-4% of the γ-hydroxy amide is formed. A variety of BINOL
and TADDOL13 derivatives were examined; the efficiencies and
enantioselectivities vary widely (see the Supporting Information).
Certain ligands derived from the TADDOL scaffold also afford
catalysts that exhibit quite high enantioselectivity. For example,
the parent TADDOL-derived phenylphosphite 5a affords 3 in 85%
ee and the corresponding (3′,5′-dimethyl)phenyl analogue 5b gives
93% ee.14 In the latter case, however, the yield of the â-hydroxya-
mide is only 60% due to competing formation of the γ-isomer (ca.
20%).
The isopropyl-, isobutyl-, and phenethyl-substituted amides 6a-c
also react with high enantioselectivity using phosphoramidite 4
(93-99% ee) although somewhat longer reaction times are required
for these more sterically congested alkenes. Hydroboration of
the trisubstituted alkene in amide 8 proceeds to less than 50%
conversion under similar reaction conditions. It might be possible
to push the reaction to completion by raising the catalyst load or
resorting to even longer reaction times; however, a simpler solution
was found. The (4′-tert-butyl)phenyl analogue, phosphite 5c, gives
a more active catalyst with this substrate. Hydroboration of 8 using
5c proceeds in good yield (79%) and high enantioselectivity (97%
ee). Again, only 3-4% of the γ-isomer is formed under the
conditions described for each substrate.
Figure 1. Use of chiral phosphites and phosphoramidites in the rhodium-
catalyzed asymmetric hydroboration of 4-substituted styrenes.
Evans and co-workers discovered that rhodium- and iridium-
catalyzed hydroborations of certain â,γ-unsaturated amides proceed
with novel regiocontrol affording predominantly the â-hydroxy
carbonyl derivatives in preference to the γ-isomers.5 The observed
regiocontrol is attributed to directing by the amide moiety;6 that
is, the reaction is apparently facilitated by favorable two-point
binding of the amide and alkene moieties to rhodium. Two-point
substrate binding also plays an important role in rhodium-catalyzed
asymmetric hydrogenation,7 an important catalytic asymmetric
reaction for which simple chiral monophosphites and phosphora-
midites are very effective ligands.8 Thus, it seemed reasonable that
rhodium-catalyzed asymmetric hydroboration also stood a good
chance of success using such ligands. Our results bear out this
expectation.9
After exploring several catalyst systems and reaction conditions,10
it was found that rhodium-catalyzed hydroboration of (E)-1 with
PinBH (0.5 mol % Rh(nbd)2BF4, 1.1 mol % BINOL-derived phos-
phoramidite 4, THF, 40 °C, 2 h) affords the â-substituted amide 2
(Figure 2). Organoboronates are useful intermediates for a variety
of subsequent reactions,11 the most common of course being the
oxidative B-to-O conversion to give the corresponding alcohol with
a retention of configuration. After oxidation with basic hydrogen
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C O M M U N I C A T I O N S
material; 2 equiv of PinBH are required for complete reaction. 11
B
NMR experiments suggest that competing formation of borate
dimers accounts for the low yield obtained with CatBH and need
for excess PinBH under these reaction conditions.16
In summary, boronate esters are useful intermediates in organic
synthesis, but the current routes to chiral boronates in high
enantiomeric purity are relatively limited.17 The efficient catalytic
asymmetric hydroboration of â,γ-unsaturated amides adds to the
synthetic arsenal as illustrated by their conversion to the â-hy-
droxycarbonyl derivatives in good yield and high enantiomeric
purity. Further studies are in progress.
Acknowledgment. Financial support for this research from the
Nebraska Research Initiative and NSF (CHE-0316825) is gratefully
acknowledged. We thank T. A. George (UNL Chemistry) for the
loan of equipment, S. Koguchi and T. J. Fisher (UNL Chemistry)
for some key preliminary experiments, and the NSF (CHE-0091975,
MRI-0079750) and NIH (SIG-1-510-RR-06307) for the NMR
spectrometers used in these studies carried out in facilities renovated
under NIH RR016544.
Returning to the observation that the (E)- and (Z)-isomers of 1
react in nearly identical yield and enantioselectivity, one plausible
explanation for their similarity is that the two isomers rapidly
interconvert and/or are converted to a common intermediate during
the course of the reaction. Sampling and analyzing the reaction
mixtures from (E)- and (Z)-1 over the course of the reaction reveals
no evidence for competing E/Z isomerism of the starting material.
Alternatively, if isomerization to a common intermediate is an
important pathway in the reaction, a likely potential intermediate
is the corresponding R,â-unsaturated amide. To explore this latter
possibility, R,â-unsaturated amide 10 was prepared. However,
treating it with Rh(nbd)2BF4, phosphoramidite 4, and PinBH effects
reduction of the alkene not hydroboration.15 For reference, the data
for amides 12a and b are shown below. From sampling and
Supporting Information Available: Experimental details and
procedures. This material is available free of charge via the Internet at
http://pubs.acs.org.
References
(1) Ma¨nnig, D.; No¨th, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 878-879.
(2) (a) Carroll, A.-M.; O’Sullivan, T. P.; Guiry, P. J. AdV. Synth. Catal. 2005,
347, 609-631. (b) Vogels, C. M.; Westcott, S. A. Curr. Org. Chem. 2005,
9, 687-699. (c) Guiry, P. J.; Saunders, C. P. AdV. Synth. Catal. 2004,
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5026. (e) Burgess, K.; Ohlmeyer, M. J. Chem. ReV. 1991, 91, 1179-
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(3) Moteki, S. A.; Wu, D.; Chandra, K. L.; Reddy, D. S.; Takacs, J. M. Org.
Lett. 2006, 8, 3097-3100 and references cited therein.
(4) Simple chiral phosphoramidites have also been shown to be very effective
ligands for the palladium-catalyzed diboration of allenes. See: Burks, H.
E.; Liu, S.; Morken, J. P. J. Am. Chem. Soc. 2007, 129, 8766-8773.
(5) (a) Evans, D. A.; Fu, G. C. J. Am. Chem. Soc. 1991, 113, 4042-4043.
(b) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem. Soc. 1992,
114, 6671-6679. (c) Evans, D. A.; Fu, G. C.; Anderson, B. A. J. Am.
Chem. Soc. 1992, 114, 6679-6685.
(6) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. ReV. 1993, 93, 1307-
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(7) Landis, C. R.; Halpern, J. J. Am. Chem. Soc. 1987, 109, 1746-1754.
(8) Bernsmann, H.; van den Berg, M.; Hoen, R.; Minnaard, A. J.; Mehler,
G.; Reetz, M. T.; de Vries, J. G.; Feringa, B. L. J. Org. Chem. 2005, 70,
943-951 and references cited therein.
(9) The elegant work of Gevorgyan et al. in which a cyclopropene carboxylic
acid ester is shown to undergo efficient asymmetric desymmetrization
using a chiral diphosphine ligand is to our knowledge the only example
of efficient directed catalytic asymmetric hydroboration reported to date.
See: Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2003,
125, 7198-7199.
analyzing aliquots from their reactions, we find that the enantiose-
lectivity is essentially unchanged over the course of the reaction.
Several other factors are important to the success of the reaction
as revealed in the course of these preliminary studies. For example,
the nature of the acyl substituent is important. In contrast to the
N-phenyl amide (E)-1, the corresponding N-benzyl amides 12b and
14 react with somewhat lower regioselectivity, 5-20% of the
γ-isomer is formed, and with lower enantioselectivity using ligands
4 or 5b, 85-87% ee. The N,N-dibenzylamide 15 behaves similarly,
87% ee accompanied by 10-25% of the γ-isomer.
(10) Data summarizing the effectiveness of several chiral ligands and reaction
solvents are included in the Supporting Information.
(11) Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003, 4695-4712.
(12) The S absolute configuration was established by conversion of the known
(S)-methyl 3-hydroxyhexanoate to (S)-3 via treatment with AlMe3 and
aniline. (a) Preparation of (S)-methyl 3-hydroxyhexanoate: Taber, D. F.;
Deker, P. B.; Silverberg, L. J. J. Org. Chem. 1992, 57, 5990-5994. (b)
Amidation: Basha, A.; Lipton, M.; Weinreb, S. M. Tetrahedron Lett. 1977,
48, 4171-4174.
(13) Seebach, D. J. Org. Chem. 1995, 60, 1788-1799.
(14) It is interesting to note that while both the (E)- and (Z)-isomers of 1 react
to completion under the optimized reaction conditions (40 °C, 2 h), their
reaction rates differ significantly. At lower temperature (25 °C, 1 mol%
catalyst loading) (Z)-1 reacts 3-4 times faster than (E)-1 using the BINOL-
derived phosphoramidite 4 as the chiral ligand. In contrast, (E)-1 reacts
2-3 times faster than (Z)-1 using the TADDOL-derived phosphite 5b
(25 °C, 1 mol% catalyst loading).
(15) Evans and Fu had previously noted that R,â-unsaturated ketones, esters,
and amides undergo efficient rhodium-catalyzed conjugate reduction rather
than hydroboration, at least for substrates capable of adopting the s-cis
geometry. See: Evans, D. A.; Fu, G. C. J. Org. Chem. 1990, 55, 5678-
5680.
(16) Our observations are consistent with the report by Robinson; see: Hadebe,
S. W.; Robinson, R. S. Eur. J. Org. Chem. 2006, 4898-4904 and
references therein.
(17) Note added in proof: Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008,
47, 145-147.
The nature of the rhodium(I) catalyst precursor is also important
to the success of the reaction. Rh(nbd)2BF4 bears a readily
dissociable counterion and is an efficient catalyst precursor. In
contrast, [Rh(nbd)Cl]2 gives only low turnover. The nature of the
borane is also important. Catecholborane (CatBH) affords product
in low yield with poor enantioselectivity under the reaction
conditions examined. Furthermore, the reaction of (E)-1 using 1
rather than 2 equiv of PinBH leads to a much diminished yield of
the â-hydroxyamide 3 (ca. 30%) along with recovered starting
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