Anti -diastereo- and enantioselective carbonyl (hydroxymethyl)allylation from the alcohol or aldehyde oxidation level: Allyl carbonates as allylmetal surrogates

Article abstract of DOI:10.1021/ja100949e

Enantioselective transfer hydrogenation of carbonate 1a in the presence of aromatic, allylic, or aliphatic alcohols 2a-2i employing a cyclometalated iridium C,O-benzoate derived from allyl acetate, 4-cyano-3-nitrobenzoic acid and (S)-SEGPHOS delivers products of (hydroxymethyl)allylation 4a-4i in good isolated yields (60-74%), good anti-diastereoselectivities (5:1-10:1 dr) and exceptional levels of enantiocontrol (93-99% ee). Under identical reaction conditions, but in the presence of isopropanol, aldehydes 3a-3i are converted to an equivalent set of adducts 4a-4i in good isolated yields (58-74%), good anti-diastereoselectivities (4:1-14:1 dr), and exceptional levels of enantiocontrol (95-99% ee). Thus, identical sets of adducts 4a-4i are produced with equal facility from the alcohol or aldehyde oxidation level. These studies represent the first general method for enantioselective carbonyl (hydroxymethyl)allylation, a process that has no highly stereoselective counterpart in conventional allylmetal chemistry.

Full text of DOI:10.1021/ja100949e

Published on Web 03/12/2010
anti-Diastereo- and Enantioselective Carbonyl (Hydroxymethyl)allylation from the
Alcohol or Aldehyde Oxidation Level: Allyl Carbonates as Allylmetal Surrogates
Yong Jian Zhang,†,‡ Jin Haek Yang,† Sang Hoon Kim,† and Michael J. Krische*,†
UniVersity of Texas at Austin, Department of Chemistry and Biochemistry, Austin, Texas 78712, and School of
Chemistry and Chemical Engineering, Shanghai Jiao Tong UniVersity, Shanghai 200240, China
Received February 2, 2010; E-mail: mkrische@mail.utexas.edu
The hydroxymethyl 1,3-diol motif appears in numerous natural
products,1-4 yet asymmetric methods for carbonyl (hydroxymethyl)-
allylation are largely unexplored.5-7 In most cases, catalytic carbonyl
hydroxymethylation has been accomplished through umpolung of
palladium π-allyl complexes derived from 2-butene-1,4-diol carboxy-
lates5 or vinyl epoxides6 in combination with metallic reductants, such
as SnCl2 or InI. However, control of regio- and diastereoselectivity
has proven challenging. Nakajima as well as Cozzi and Umani-Ronchi
each report a single example of catalytic syn-(hydroxymethyl)allylation,
but only moderate enantioselectivities were observed.7 To our knowl-
edge, corresponding protocols for enantioselective anti-(hydroxym-
ethyl)allylation are unknown.8
1a was exposed to benzyl alcohol 2a in the presence of the
cyclometalated complex derived from [Ir(cod)Cl]2, 4-cyano-3-nitroben-
Table 1. Enantioselective (Hydroxymethyl)allylation from the
Alcohol Oxidation Levela
We have found that chiral ortho-cyclometallated iridium C,O-
benzoates catalyze carbonyl allylation,9a,b,e-h crotylation,9c,f
tert-prenylation9d,f and (alkoxy)allylation9i employing allyl acetate,
R-methyl allyl acetate, 1,1-dimethylallene and allyl gem-dibenzoates
as allyl donors, respectively. For such C-C bond forming transfer
hydrogenations,10 alcohols function as both hydrogen donors and
carbonyl precursors, enabling identical sets of carbonyl addition
products to be generated from either the alcohol or aldehyde
oxidation level. In more recent work, it was found that use of the
isolated iridium C,O-benzoate complex was essential for efficient
reductive couplings of allylic gem-dibenzoates.9i This outcome
prompted us to reexamine processes that failed using in situ
generated catalysts, including reactions of allylic carbonates.
Here, we report that complex (S)-I, which is modified by the
chiral phosphine ligand (S)-SEGPHOS,12 serves as a single-
component catalyst for the coupling of cyclic carbonate 1a to
alcohols 2a-2i to furnish (hydroxymethyl)allylation products 4a-4i
in a highly enantiomerically enriched form. Under similar conditions
in the presence of isopropanol, cyclic carbonate 1a couples to
aldehydes 3a-3i to furnish an identical set of adducts 4a-4i with
comparable levels of selectivity. These studies represent the first
general method for enantioselective carbonyl (hydroxymethyl)al-
lylation, a process that has no highly stereoselective counterpart in
conventional allylmetal chemistry.
a Yields are of material isolated by silica gel chromatography.
Enantiomeric excess was determined by chiral stationary phase HPLC
analysis. See Supporting Information for further details.
Table 2. Enantioselective (Hydroxymethyl)allylation from the
Aldehyde Oxidation Levela
A principal concern regarding use of cyclic carbonate 1a is the
requirement that alcohols 2 selectively dehydrogenate in the presence
of diol-containing products 4. To probe this issue and to explore the
feasibility of utilizing allylic carbonates as allyl donors, cyclic carbonate
† University of Texas at Austin.
‡ Shanghai Jiao Tong University.
a As described for Table 1.
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4562 J. AM. CHEM. SOC. 2010, 132, 4562–4563
10.1021/ja100949e  2010 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Conversion of Diol 4c to Compounds 5c, 6c, and 7ca
Acknowledgment. Acknowledgment is made to the Robert A.
Welch Foundation and the NIH-NIGMS (RO1-GM069445). Dr.
Yasunori Ino and Dr. Wataru Kuriyama of Takasago are thanked
for the generous donation of (S)-SEGPHOS. Y.J.Z. acknowledges
partial financial support from Shanghai Jiao Tong University.
Supporting Information Available: Experimental procedures,
spectral data for new compounds, including scanned images of HPLC
traces, as well as H and 13C NMR spectra. This material is available
free of charge Via the Internet at http://pubs.acs.org.
1
a Reagents: (a) NaH, TsCl, THF, 82%; (b) n-BuLi, THF, 92%; (c) NaH,
H2CdCHCH2Br, THF, 82%; (d) Grubbs I, DCM, 90%; (e) TBSCl, Et3N,
DMAP, DCM, 88%; (f) NaH, H2CdCHCH2Br, THF, 90%; (g) Grubbs I,
DCM, 91%. See Supporting Information for further details.
References
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zoic acid, allyl acetate, and BIPHEP (2,2′-bis(diphenylphosphino)bi-
phenyl). Remarkably, decarboxylative anti-(hydroxymethyl)allylation
occurs smoothly to furnish the desired diol 4a in good isolated yield.
Dehydrogenation of the diol product is not observed as the homoallylic
olefin of 4a binds the single remaining coordination site essential for
ꢀ-hydride elimination.10d,11 Exclusive formation of the branched
regioisomer and anti-diastereoselectivity are consistent with carbonyl
addition from the primary (E)-σ-allyl iridium haptomer by way of a
chairlike transition structure. Finally, unlike analogous reactions of
allylic acetates which require added base,9a-c,e-i the decarboxylative
process occurs in the absence of base or any additive.
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chiral phosphine ligand (S)-SEGPHOS,12 was superior. By simply
combining carbonate 1a with alcohols 2a-2i in the presence of
(S)-I in THF solvent at 90 °C, products of (hydroxymethyl)allylation
4a-4i are generated with good anti-diastereoselectivities (5:1-10:1
dr) and exceptional levels of enantiocontrol (93-99% ee). The
isolated yields were moderate (60-74%) due to incomplete
consumption of alcohols 2a-2i (Table 1). Higher yields are
obtained if the reaction time is extended.
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Aldehydes 3a-3i are converted to an equivalent set of adducts
4a-4i under similar conditions employing isopropanol as the
terminal reductant. Comparable isolated yields (58-74%), anti-
diastereoselectivities (4:1-14:1 dr), and enantioselectivities (95-99%
ee) are observed (Table 2). Thus, identical adducts 4a-4i are
produced with equal facility from the alcohol or aldehyde oxidation
level. Construction of oxetane 5c in two steps from adduct 4c serves
to illustrate the utility of the (hydroxymethyl)allylation process.
Similarly, pyrans 6c and 7c are prepared in three and two steps
from adduct 4c, respectively (Scheme 1).
The ability of allylic carbonate 1a to participate in intermolecular
decarboxylative C-C bond forming transfer hydrogenation prompted
us to investigate the decarboxylative C-C coupling of allyl-benzyl
carbonates 1b and 1c. Remarkably, using the achiral iridium catalyst
BIPHEP-I, the desired products of C-C bond formation 8 and 9
were produced in modest yield along with recovered benzyl alcohol.
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conversion in the iridium catalyzed carbonyl allylations we describe,
high-yielding decarboxylative C-C coupling of allyl carbonates
will require improved second-generation catalysts.
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moiety of allylic alcohols such as cinnamyl alcohol 2f (five-membererd versus
four-membered chelate). Thus, alcohol reactants 2a-2i dehydrogenate whereas
homoallylic alcohol products do not.
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lective carbonyl (hydroxymethyl)allylation. Future studies will focus
on the development of related C-C couplings of alcohols and
π-unsaturated reactants.
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