Cation control of diastereoselectivity in iridium-catalyzed allylic substitutions. formation of enantioenriched tertiary alcohols and thioethers by allylation of 5H-oxazol-4-ones and 5H-thiazol-4-ones

Article abstract of DOI:10.1021/ja410650e

We report highly diastereo- and enantioselective allylations of substituted 5H-oxazol-4-ones and 5H-thiazol-4-ones catalyzed by a metallacyclic iridium complex. Enantioselective Ir-catalyzed allylation of substituted 5H-oxazol-4-ones occurs with high diastereoselectivity by employing the corresponding zinc enolates; enantioselective Ir-catalyzed allylation of substituted 5H-thiazol-4-ones occurs with the corresponding magnesium enolates with high diastereoselectivity. The allylation of substituted 5H-oxazol-4-ones provides rapid access to enantioenriched tertiary α-hydroxy acid derivatives unavailable through Mo-catalyzed allylic substitution. The allylation of substituted 5H-thiazol-4-ones provides a novel method to synthesize enantioenriched tertiary thiols and thioethers. The observed cation effect implies a novel method to control the diastereoselectivity in Ir-catalyzed allylic substitution.

Full text of DOI:10.1021/ja410650e

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Article
Cation Control of Diastereoselectivity in Iridium-Catalyzed Allylic
Substitutions. Formation of Enantioenriched Tertiary Alcohols and
Thioethers by Allylation of 5H-Oxazol-4-ones and 5H-Thiazol-4-ones
Wenyong Chen, and John F. Hartwig
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 02 Dec 2013
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Journal of the American Chemical Society
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Cation Control of Diastereoselectivity in Iridium-Catalyzed Allylic
Substitutions. Formation of Enantioenriched Tertiary Alcohols and
Thioethers by Allylation of 5H-Oxazol-4-ones and 5H-Thiazol-4-ones
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Wenyong Chen and John F. Hartwig*
Department of Chemistry, University of California, Berkeley, California 94720, and Division of Chemical Sciences,
Lawrence Berkeley National Laboratory, United States
ABSTRACT: We report a highly diastereo- and enantioselective allylation of substituted 5H-oxazol-4-ones and 5H-
thiazol-4-ones catalyzed by the metallacyclic iridium complex. Enantioselective Ir-catalyzed allylation of substituted 5H-
oxazol-4-ones occurs with high diastereoselectivity by employing the corresponding zinc enolates; enantioselective Ir-catalyzed
allylation of substituted 5H-thiazol-4-ones requires the corresponding magnesium enolates to achieve high diastereoselectivity. The
allylation of substituted 5H-oxazol-4-ones provides rapid access to enantioenriched tertiary α-hydroxy acid derivatives unavailable
through Mo-catalyzed allylic substitution. The allylation of substituted 5H-thiazol-4-ones provides a novel method to synthesize
enantioenriched tertiary thiols and thioethers. The observed cation effect implies a novel method to control the diastereoselectivity
in Ir-catalyzed allylic substitution.
Most recently, Stoltz reported the construction of vicinal tertiary
INTRODUCTION.
and quaternary stereocenters by conducting reactions with an
Enantioselective allylic substitution reactions catalyzed by
metallacyclic iridium complexes derived from phosphoramidites
have become a powerful tool to construct carbon-heteroatom and
carbon-carbon bonds. These reactions have now been applied to
the synthesis of a wide range of natural products and pharmaceu-
tically important compounds.1 High regio- and enantioselectivity
is generally achieved with a variety of heteroatom2 and carbon
nucleophiles.3 However, obtaining high diastereoselectivity in the
Ir-catalyzed enantioselective allylation has been challenging.
iridium complex ligated by a phosphoramidite ligand derived
from 2-methyl-1,2,3,4-tetrahydroquinoline. This reaction led to
the allylation of β-ketoesters.8 Finally, Trost reported a series of
Mo-catalyzed diastereo- and enantioselective allylic substitutions
with azlactones, oxazolones, oxindoles and cyanoesters.9 Alt-
hough progress has been made, the scope of nucleophiles suitable
for highly diastereo- and enantioselective Ir-catalyzed allylic sub-
stitution is limited to those just described. Thus, the application of
Ir-catalyzed allylic substitution has been restricted to the synthesis
of enantioenriched amines and specific classes of enantioenriched
carbonyl compounds (Scheme 1).
Scheme 1. Ir-Catalyzed Diastereo- and Enantioselective
Allylic Substitution
FIGURE 1. Substituted 5H-Oxazol-4-ones and 5H-Thiazol-4-
ones
Herein, we present Ir-catalyzed diastereo- and enantioselec-
10
tive allylation of substituted 5H-oxazol-4-ones9b,
and 5H-
thiazol-4-ones as a means to prepare enantioenriched tertiary al-
cohols and enantioenriched tertiary thiols and thioethers (Figure
1). The Ir-catalyzed allylation of substituted 5H-oxazol-4-ones
occurs with high diastereoselectivity when the reaction is con-
ducted with zinc enolates generated from diethylzinc, and the
allylation of substituted 5H-thiazol-4-ones occurs with high dia-
stereoselectivity when the reaction is conducted with magnesium
enolates generated from magnesium bis(diisopropyl)amide. These
reactions of 5H-oxazol-4-ones provide rapid access to enantioen-
riched α-hydroxy acid derivatives, which are readily converted to
enantioenriched tertiary alcohols containing a vicinal tertiary chi-
ral center. The reactions of 5H-thiazol-4-ones are the first transi-
We recently reported an approach to obtain high diastereoselec-
tivity by conducting reactions with an optically inactive silver
phosphate as a co-catalyst.4 This transformation was the first
highly diastereo- and enantioselective intermolecular allylic sub-
stitution catalyzed by an iridium-phosphoramidite system5 and
revealed a useful method to access tertiary amines containing a
vicinal tertiary stereocenter.6 Following this work, Carreira re-
ported diastereo- and enantioselective Ir-catalyzed allylation of
tertiary aldehydes by employing a chiral amine as the co-catalyst.7
The reaction provides a new method for generating products con-
taining vicinal tertiary and all carbon quaternary stereocenters.
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Page 2 of 7
14i,j
2c
3b
Et2Zn
89(86)
12.0:1
99
tion metal-catalyzed reactions of this class of nucleophile, and
these reactions provide rapid access to enantioenriched tertiary
thiols and thioethers containing a vicinal tertiary stereocenter.
Whereas prior studies have shown that the diastereoselectivity can
be modulated by anions, the current studies show that the dia-
stereoselectivity can be controlled by cations, particularly when
changing the anion fails to improve diastereoselectivity.
1
2
3
4
5
6
7
8
a1.00 equiv of cinnamyl compounds, 1.20 equiv of 3, 0.60 equiv
of base unless noted otherwise. See the Supporting Information
(SI) for experimental details. The absolute configuration of the
allylation product was assigned by analogy. Determined by H
NMR analysis with mesitylene as the internal standard. The num-
b
1
c
bers in parentheses correspond to the isolated yield. Determined
1
d
by H NMR analysis of the crude reaction mixture. Determined
by chiral HPLC analysis of the major diastereomer. e2-tert-
Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-
RESULTS AND DISCUSSION
9
diazaphosphorine (BEMP) f1,5,7-Triazabicyclo[4.4.0]dec-5-ene
(TBD) g1.20 equiv of Et2Zn. h80% conversion of cinnamyl acetate.
Ir-catalyzed allylic substitution with substituted 5H-
oxazol-4-ones
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iCPME was used as the solvent instead of toluene. Preformed
j
The reaction of cinnamyl methyl carbonate 2a with 2-phenyl-
5-methyloxazol-4(5H)-one (3a) was first investigated to evaluate
the effect of the base on reactivity and diastereoselectivity (Table
1). The reaction catalyzed by [Ir(COD)Cl]2, phosphoramidite L1
and the silver phosphate 4 failed to effect the desired allylation
reaction in the absence of base, presumably because of the low
basicity of the phosphate (entry 1). Therefore, reactions were
examined with various organic and inorganic bases stronger than
the phosphate (entries 2-7). All of the reactions provided the
branched product exclusively in high yield. Among them, the
reaction with 0.60 equiv of Et2Zn occurred with the highest dia-
stereoselectivity (dr 5.0:1, entry 7). When the same reaction was
conducted with equivalent amounts of Et2Zn and 3a, the reaction
yielded the product with low diastereoselectivity (dr 1.7:1, entry
8). Thus a 1:2 ratio of Et2Zn to the nucleophile 3a was important
for the reaction to occur with high diastereoselectivity.
catalyst 1 was used instead of the in situ generated catalyst.
Table 2. Ir-Catalyzed Allylic Substitution with 5H-Oxazol-
4-ones a, b
Table 1. Evaluation of the Reaction Conditions in the Ir-
Catalyzed Allylation of Substituted 5H-Oxazol-4-onesa
Entry
1
Substrate
2a
Nu
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
base
None
Yield(%)b
drc
ee(%)d
-
0
-
2
2a
quinine
BEMPe
TBDf
92
90
87
84
61
90
44
45
55h
86
86
86
3.0:1
2.9:1
2.2:1
2.2:1
1.8:1
5.0:1
1.7:1
4.0:1
4.3:1
5.8:1
6.0:1
9.0:1
99
99
98
98
99
99
99
99
99
99
99
99
3
2a
4
2a
5
2a
(MeO)2Zn
Mg(NiPr2)2
Et2Zn
6
2a
7
2a
8g
2a
Et2Zn
9
2b
Et2Zn
10
11
12
13i
2c
Et2Zn
2a
Et2Zn
aSee the SI for experimental details. bAbsolute configurations
were assigned by analogy. The dr’s were determined by H NMR
2c
Et2Zn
1
2c
Et2Zn
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analysis of the crude reaction mixtures. The ee’s were determined
by chiral HPLC analysis of the major diastereomer.
aliphatic allylic carbonates or acetates reacted in good yield but
with low diastereoselectivity.
1
2
Mo-catalyzed diastereo- and enantioselective allylation of
substituted 5H-oxazol-4-ones was reported by Trost and
coworkers, but the Mo-catalyzed reactions generated a different
diastereomer from that formed in the Ir-catalyzed allylation.9b
Since the previous report established the configuration only by
analogy to the allylation products of azlactones, we chose to ob-
tain a suitable crystal of the compound in entry 8 of Table 2 to
unambiguously establish the absolute stereochemistry as (R,R).12
A comparison of Mo-catalyzed and Ir-catalyzed allylation of 5H-
oxazolones shows the complementarity of the diastereoselectivity
in the two systems. This complementary selectivity might be gen-
eral because the two reactions proceed through different mecha-
nisms. Ir-catalyzed allylic substitution forms the C-C bond with
inversion of configuration by nucleophilic attack on the allyl in-
termediate,13 whereas the Mo catalyzed allylic substitutions form
the C-C bond with retention of configuration, perhaps through an
inner-sphere reductive elimination.14
A variety of leaving groups on the cinnamyl ester and aryl
groups on the oxazolone were examined to assess the effect of the
structure of the electrophile and nucleophile on diastereoselectivi-
ty (entries 9-12). Although the reaction between cinnamyl acetate
2c and 3a occurred to low conversion, the reaction between 2c
and 2-(4-methoxyphenyl)-5-methyloxazol-4(5H)-one (3b) pro-
ceeded smoothly to furnish the product with high diastereoselec-
tivity (dr 6.0:1, entry 12). The higher reactivity of 3b may be ra-
tionalized by the electron-donating ability of the PMP group. The
same reaction conducted in cyclopentyl methyl ether (CPME)
provided the product with even higher diastereoselectivity (dr
9.0:1, entry 13).11
The preformed catalyst was utilized to evaluate the effect of
the silver phosphate. The reaction catalyzed by the preformed
catalyst 1 proved to be most selective, affording the product with
high yield, enantioselectivity and diastereoselectivity (89% yield,
dr 12:1, 99% ee, entry 13). This result is consistent with the pre-
vious report that the silver ion sequesters chlorides and promotes
the formation of the metallacyclic iridium complex.4 The presence
of the phosphate as the anion to the metallacyclic iridium cation
led to slightly lower diastereoselectivity in this reaction. Thus,
subsequent reactions were conducted with the neutral preformed
catalyst 1 instead of the in situ generated catalyst containing the
phosphate as the counteranion.
The scope of reactions of substituted cinnamyl acetates with
3b was explored under the conditions of entry 14 in Table 1. Var-
ious para-substituted cinnamyl acetates possessing diverse elec-
tronic properties were examined (Table 2). The reactions with
cinnamyl acetates containing a halogen in the para position gave
the products in high yields with good diastereo- and enantioselec-
tivities (entries 1-3). The substrate containing a strong electron-
withdrawing group, such as trifluoromethyl, in the para position
afforded the product in 90% yield with 12:1 dr and >99% ee (en-
try 4), and reactions of cinnamyl acetates possessing electron-
donating groups yielded the product with good diastereoselectivi-
ty (80-90% yield, 11:1 – 13:1 dr, 98-99% ee, entries 5 and 6).
The substrate containing fluorine in the meta position reacted in
high yield and selectivity (83% yield, dr 14:1, >99% ee, entry 7);
3,4-dichlorocinnamyl acetate also reacted with 3b in high yield
and selectivity (91% yield, dr 18:1, 99% ee, entry 8).
The reactions of heteroaryl-substituted allyl acetates were also
examined. The allyl acetate containing an indolyl group reacted in
the yield and selectivity comparable to those of the cinnamyl ace-
tates (80% yield, 11:1 dr, 99% ee, entry 9). The allyl acetate con-
taining a furyl group also reacted with 3b to deliver the product in
high yield with moderate diastereoselectivity (92% yield, dr 6:1,
99% ee, entry 10).
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Ir-catalyzed allylic substitution with substituted 5H-
thiazol-4-ones
Encouraged by the success of Ir-catalyzed allylation of substi-
tuted 5H-oxazol-4-ones, we investigated Ir-catalyzed allylic sub-
stitution with substituted 5H-thiazol-4-ones. Substituted 5H-
thiazol-4-ones have been known to exist in equilibrium with sub-
stituted 4-hydroxythiazoles (Figure 1).15 4-Hydroxythiazole is
usually the thermodynamically favored tautomer in polar solvents
such as DMSO. These compounds can be conveniently synthe-
sized through the condensation between α-haloacid chlorides and
thiobenzamides.15b Although 5H-thiazol-4-ones resemble 5H-
oxazol-4-ones, their synthetic potential in transition metal-
catalyzed reactions has not been tapped.16
Table 3. Evaluation of the Reaction Conditions in the Ir-
Catalyzed Allylation of 5aa
Entry
Substrate
base
quinine
Yield(%)b
75
b:lc
drc
ee(%)d
1
2
3
4
5
2a
2a
2a
2a
2b
>20:1
>20:1
>20:1
>20:1
>20:1
1.2:1
1.3:1
6.0:1
6.8:1
10.4:1
-
Et2Zn
86
-
MgBu2
29-85
83(83)
88(88)
99
99
99
Mg(NiPr2)2
Mg(NiPr2)2
a1.00 equiv of cinnamyl compounds, 1.20 equiv of 5a, 0.60 equiv
of base unless noted otherwise. See the SI for experimental details.
Absolute configuration of the allylation product was assigned by
analogy. bDetermined by 1H NMR analysis with mesitylene as the
internal standard. Numbers in parentheses correspond to the iso-
The reactions of various substituted 5H-oxazol-4-ones were
also examined. The reaction of cinnamyl acetate with 5H-oxazol-
4-ones 3c and 3d containing ethyl and isopropyl substituents pro-
ceeded smoothly with high stereoselectivity (82-93% yield, 9:1 –
11:1 dr, 98->99% ee, entries 11-12). The reaction with isobutyl-
substituted 3e yielded the product in good yield with moderate
diastereoselectivity and excellent enantioselectivity (80% yield,
6:1 dr, >99% ee, entry 13). Even the reaction with 5H-oxazol-4-
ones containing a benzyloxyethyl substituent (3f) that can be fur-
ther derivatized occurred in high yield with high stereoselectivity
(83% yield, 12:1 dr, 99% ee, entry 14). Under these conditions,
c
1
lated yield. Determined by H NMR analysis of the crude reac-
d
tion mixture. Determined by chiral HPLC analysis of the major
diastereomer.
The reaction of cinnamyl methyl carbonate with 2-phenyl-5-
methylthiazol-4(5H)-one (5a) was investigated to evaluate the
effect of base on reactivity and diastereoselectivity (Table 3). In
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the presence of the preformed catalyst 1 and quinine, the reaction
The scope of the reaction of substituted cinnamyl t-butyl car-
1
2
3
4
5
6
7
8
delivered the allylation product 6 in 75% yield, 1.2:1 dr and >20:1
branched to linear ratio (entry 1). Although the structure of 5H-
thiazolones is very similar to that of 5H-oxazolones, the allylation
product 6 formed in only 1.3:1 dr when Et2Zn was employed as
the base (entry 2). By contrast, the reaction gave 6 in a higher
6.0:1 dr when MgBu2 was employed as the base (entry 3). The
yield of the reaction, however, was variable because MgBu2 could
also act as a nucleophile and led to undesired side reactions.
To avoid the undesired side reactions, we studied the effect of
non-nucleophilic bases. The reaction with Mg(NiPr2)2 led to a
reproducible reaction that formed the product in 83% yield with
6.8:1 dr (entry 4). Further examination of the leaving group
showed that the reaction of cinnamyl t-butyl carbonate yielded the
allylation product with the highest diastereoselectivity (88% yield,
10.4:1 dr, 99% ee, entry 5).
bonate with 5a was investigated under the aforementioned condi-
tions (Table 4). All the reactions occurred in >20:1 branched to
linear ratio. Various para-substituted cinnamyl t-butyl carbonates
possessing diverse electronic properties underwent the allylation
reaction smoothly to provide the products in high yields, dia-
stereo- and enantioselectivities (Table 4, entries 1-8). A suitable
crystal of the substitution product (entry 2) was obtained to un-
ambiguously establish the absolute stereochemistry.17 As expected,
the configuration of the product is the same as that of products
from the allylation of 5H-oxazolones.
The reactions of heteroaryl-substituted allyl t-butyl carbonate
were also examined. The allyl carbonate containing an indolyl
group reacted like the cinnamyl carbonates (90% yield, 7:1 dr,
98% ee, entry 9). The allyl carbonate containing a furyl group
reacted with 5a to deliver the product in high yield with moderate
diastereoselectivity (82% yield, dr 5:1, >99% ee, entry 10).
The reactions of various substituted 5H-thiazolones were also
examined. The reaction of cinnamyl t-butyl carbonate with the
5H-thiazolone 5b containing an ethyl substituent proceeded
smoothly with high stereoselectivity (81% yield, 9:1 dr, 99% ee,
entry 11). The reaction with benzyl-substituted 5c yielded the
product in good yield with moderate diastereoselectivity and ex-
cellent enantioselectivity (79% yield, 4:1 dr, 98% ee, entry 12).
Furthermore, the reaction with 5d containing a thioether moiety
occurred in high yield with high stereoselectivity (75% yield, 7:1
dr, >99% ee, entry 13). So far, aliphatic allylic carbonates have
reacted in good yield but with low diastereoselectivity.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
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40
41
42
43
44
45
46
47
48
49
50
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55
56
57
58
59
60
Table 4. Ir-Catalyzed Allylic Substitution with 5H-thiazol-
4-ones a, b
Functionalization of the allylation product of 5H-
oxazol-4-ones and 5H-thiazol-4-ones
The transformations of the products from allylation of substi-
tuted 5H-oxazol-4-ones provides a rapid access to enantioenriched
tertiary α-hydroxy acids,18 which are common substructures in
biologically active compounds.19 Four of the possible transfor-
mations of the product are shown in Scheme 2. The allylation
product 7 was rapidly hydrolyzed to α-hydroxy amide 8a in
o
NaOH at 80 C. In addition, the substitution product 7 was trans-
formed to a terminal alcohol 8b through a sequence of hydrobora-
tion and oxidation.
Scheme 2. Transformations of the Allylic Substitution Product
a2.5 N NaOH, EtOH, reflux, 86% yield; b9-BBN, THF; then
c
NaBO3·4H2O, 67% yield; (i) 2.5 N NaOH, EtOH, reflux; (ii) H2,
Pd/C; (iii) PhI(OOCCF3)2, CH3CN, 81% yield for 3 steps, 99% ee;
d(i) 9-BBN, THF; then PhI, Pd(dppf)Cl2, K2CO3; (ii) 2.5 N NaOH,
EtOH, reflux; (iii) PhI(OOCCF3)2, CH3CN, 51% yield for 3 steps.
aSee the SI for experimental details. bAbsolute configurations
1
were assigned by analogy. The dr’s were determined by H NMR
The 5H-oxazol-4-one moiety also can serve as an acyl anion
equivalent. Following hydrolysis and hydrogenation, Hofmann
analysis of the crude reaction mixtures. The ee’s were determined
by chiral HPLC analysis of the major diastereomer.
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rearrangement20 converted 7 to the ketone 8c containing a tertiary
center.1 The current work demonstrates that the facial selectivity
1
2
3
4
5
6
7
8
stereogenic center. These transformations occurred without loss of
enantiopurity. Thus, the new sequence provides a method to syn-
thesize enantioenriched acyclic tertiary α-aryl ketones, which are
of both prochiral nucleophiles and allyl electrophiles can be con-
trolled in the transition state for allylation of valuable, cyclic car-
boxylic acid derivatives. The metallacyclic iridium complex con-
trols the facial selectivity of the allyl electrophile. The properties
of the enolate counterion have a large effect on the facial selec-
tivity of the prochiral nucleophiles, and we have shown that judi-
cious choice of this counterion can lead to reactions that occur
with high diastereoselectivities. Therefore, the combination of
metallacyclic iridium catalyst and appropriate nucleophile should
allow a wide range of diastereo- and enantioselective reactions
that form products containing vicinal stereocenters.
The origin of the dramatic effect of the cation on diastereose-
lectivity is difficult to clearly define at this time. However, we
propose that the aggregation states of metal enolates are important.
Zinc enolates and magnesium enolates are not monomeric and
have been shown to adopt aggregation states ranging from dimers
to tetramers, with the aggregation states of magnesium enolates
typically being higher than those of zinc enolates.26 Further stud-
ies to explore the origin of the effect of cations and aggregation
state, as well as studies to expand the scope of nucleophiles and
electrophiles that react with high diastereoselectivity, are ongoing
in this laboratory.
difficult to access by enantioselective α-arylation of ketones.21
A
sequence of hydroboration and Suzuki coupling can be conducted
prior to the sequence of hydrolysis and Hofmann rearrangement to
generate a homologated product. For example, this reaction se-
quence conducted with the substitution product 7 yielded the en-
antioenriched ketone 8d.
The importance of organosulfur compounds in both organic
synthesis22 and biological studies has led to progress in the
asymmetric synthesis of thiols and thioethers.23 Most of these
methods, however, focused on the enantioselective synthesis of
secondary thiols and thioethers.24 The only catalytic synthesis of
enantioenriched tertiary thioethers was a recent enantioselective
thia-Michael addition to nitro alkenes catalyzed by a chiral thiou-
rea.25
The product from allylation of 5H-thiazol-4-ones is a valuable
precursor to access enantioenriched tertiary thioethers containing
a vicinal tertiary chiral center. The reaction in eq 1 shows that the
thiazolone compound can be readily converted to an enantioen-
riched tertiary thioether under basic conditions. The product of
this hydrolysis contains two common functional groups – an al-
kene and an amide – that allow for further modification.
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ASSOCIATED CONTENT
Experimental procedures and characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*jhartwig@berkeley.edu
CONCLUSIONS
Notes
The authors declare no competing financial interest.
In summary, we have developed the Ir-catalyzed diastereo-
and enantioselective allylation of substituted 5H-oxazol-4-ones
and 5H-thiazol-4-ones. The key to achieving high diastereoselec-
tivity for the allylation of substituted 5H-oxazol-4-ones proves to
be the use of zinc enolates as the nucleophile. The key to achiev-
ing high diastereoselectivity for the allylation of substituted 5H-
thiazol-4-ones proves to be the use of magnesium enolates as the
nucleophile. Thus, the cation bound to the enolate can have a
pronounced positive effect on the diastereoselectivity of this al-
lylation chemistry.
The iridium-catalyzed allylation of oxazolones forms the dia-
stereomer complementary to the outcome of the molybdenum-
catalyzed allylation. The allylation products can be easily func-
tionalized to various building blocks, including enantioenriched
tertiary α-hydroxyl acid derivatives and tertiary α-arylated ketones.
The reaction to form ketones demonstrates that 5H-oxazol-4-one
can serve as an acyl anion equivalent in organic transformations.
The iridium-catalyzed allylation of thiazolones demonstrates
that substituted 5H-thiazolones can undergo transition metal-
catalyzed enantioselective reactions. This heterocycle is a valua-
ble nucleophile because the allylation products can be readily
converted to enantioenriched tertiary thiols and thioethers contain-
ing a vicinal tertiary stereocenter.
ACKNOWLEDGMENT
We thank the NIH (GM-58108) for work on methods develop-
ment, the Director, Office of Science, of the U.S. Department of
Energy under Contract No. DE-AC02-05CH11231 for support of
our studies on effects of the outer coordination sphere, Johnson-
Matthey for gifts of [Ir(cod)Cl]2, and Dr. Klaus Ditrich and BASF
for a generous gift of chiral amines.
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