Copper(I)-catalyzed substitution of propargylic carbonates with diboron: Selective synthesis of multisubstituted allenylboronates

Article abstract of DOI:10.1021/ja806602h

A versatile synthetic method for the preparation of the allenylboronates, Cu(I)-catalyzed reaction of propargylic carbonates with a diboron, is described. A Cu(O-t-Bu)-Xantphos catalyst system was effective for the preparation of various allenylboron comp

Full text of DOI:10.1021/ja806602h

Published on Web 10/31/2008
Copper(I)-Catalyzed Substitution of Propargylic Carbonates with Diboron:
Selective Synthesis of Multisubstituted Allenylboronates
Hajime Ito,* Yusuke Sasaki, and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido UniVersity, Sapporo 060-0810, Japan
Received August 20, 2008; E-mail: sawamura@sci.hokudai.ac.jp; hajito@sci.hokudai.ac.jp
Allenylboron compounds are potentially general synthetic reagents
that could be used for various transformations; however, their avail-
ability is limited as compared to the other corresponding allenylmetal
reagents such as allenyltins and allenylsilanes.1-4 Multisubstituted
allenylboronates with different alkyl groups on the R- and γ-carbons
as well as those bearing functional groups or axial chirality are still
difficult to prepare. We report here a versatile synthetic method for
the preparation of the allenylboronates, Cu(I)-catalyzed reaction of
propargylic carbonates with a diboron derivative. A Cu(O-t-
Bu)-Xantphos catalyst system5,6 appeared to be effective for the
preparation of various allenylboronates with different substitution
patterns, including R,γ,γ-trisubstituted,7 R,γ-disubstituted, and R-mono-
substituted derivatives. Moreover, the allenylboron synthesis tolerated
functional groups such as ester, carbamate, and silyl ether. The reaction
with an optically active propargylic alcohol derivative proceeded with
complete chirality transfer, giving an axially chiral allenylboronate with
high enantiomeric purity.8 The Lewis acid promoted aldehyde addition
forming homopropargylic alcohols showed the usefulness of the new
allenylboronates.9
allenylboron synthesis tolerated functional groups such as ester (3k),
carbamate (3l), and silyl ether (3m) (Table 1, entries 10-12).
Accordingly, this method should be useful for the synthesis of complex
molecules.
Combined with Lewis acid promoted addition of the allenylbo-
ronates to aldehydes, the present Cu(I)-catalysis offers a general
route to homopropargylic alcohols (Scheme 1).13 Conversion of
propargylic carbonate 1n (R1 ) c-Hex, R2 ) H, R3 ) Bu) to the
corresponding R,γ-disubstituted allenylboronates14 and subsequent
Table 1. Reaction of Propargylic Carbonates 1 and Diboron 2a
The reaction of propargylic carbonate 1a with bis(pinacolato)diboron
(2, 2.0 equiv) in the presence of Cu(O-t-Bu)/Xantphos catalyst (10
mol %) at 50 °C in THF completed in 1 h to give trisubstituted
allenylboronate 3a, having three different alkyl groups7 on the allene
moiety, in 93% GC yield (eq 1). This is a “formal SN2′ substitution”
of a propargylic system with a boryl nucleophile. No “SN2-type product
(propargylic boronate)” was detected in the reaction mixture. Reactions
with other phosphine ligands resulted in lower yields under otherwise
identical conditions (PPh3: 58%, dppe: 25%, dppp: 43%, dppf: 66%,
no ligand: trace).10
This Cu(I)-catalysis showed a broad substrate scope toward synthesis
of various allenylboron compounds (Table 1). Trialkyl-substituted
allenylboronates 3b,c were also formed in high yields (97% and 90%,
entries 1 and 2, respectively). The carbonates involving six- and five-
membered rings (1d,e) were converted into allenylboronates containing
allenylidenecyclohexane (3d) and allenylidenecyclopentane (3e) struc-
tures, respectively (entries 3 and 4). Allenylboronate 3f with a phenyl
group at the R-position of the boryl group was, however, obtained in
only a low yield (22% yield, entry 5).11
Although R,γ-disubstituted (3g,h) and R-monosubstituted alle-
nylboronates (3j) were also obtained in good and moderate yields
(Table 1, entries 6, 7, and 9),12 γ,γ-disubstituted compound 3i could
not be prepared (entry 8). The latter is probably due to the high
reactivity of the C-H bond at the alkyne terminus of 1i. This
a Conditions: 1 (0.5 mmol); 2, (1.0 mmol); Cu(O-t-Bu) (10 mol %,
0.05 mmol); Xantphos (10 mol %, 0.05 mmol); THF (0.5 mL). b 1H
NMR yield of the crude mixture. Isolated yield is shown in parentheses.
c The reaction was carried out at 70 °C.
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10.1021/ja806602h CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
addition reaction with benzaldehyde in the presence of BF3 ·OEt2
furnished syn-homopropargylic alcohol 4a with a high diastereo-
selectivity (anti/syn 6:94, 53%).9,15-17 Reaction of the R,γ,γ-
trisubstituted allenylboronate, which was prepared from carbonate
1b (R1 ) R2 ) Me, R3 ) PhCH2CH2), with benzaldehyde and
isobutyraldehyde gave the corresponding homopropargylic alcohols
(4b: 90%, 4c: 60%) involving a sterically congested alcohol moiety
with an adjacent quaternary carbon center.
References
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Scheme 1. Synthesis of Homopropargylic Alcohols 4 via Lewis
Acid Catalyzed Reaction of Allenylboronates 3 and Aldehydes
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(5) We reported earlier efficient catalytic properties of the Cu(O-t-Bu)-
Xantphos system in some reactions. For the dehydrogenative alcohol
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Org. Lett. 2005, 7, 1869–1871. For the regioselective and stereoselective
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alkynes to aldehyde, see: (e) Asano, Y.; Hara, K.; Ito, H.; Sawamura, M.
Org. Lett. 2007, 9, 3901–3904. (f) Asano, Y.; Ito, H.; Hara, K.; Sawamura,
M. Organometallics 2008, 27, in press. For studies with Cu(I)/Xantphos
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Optically active carbonate (S)-1h (97% ee) was converted to
chiral allenylboronate [(S)-3h]. A subsequent BF3-promoted addition
reaction of (S)-3h with isobutyraldehyde afforded homopropargylic
alcohols anti-(3S,4R)-4d and syn-(3R,4R)-4d in 89% yield with
good diastereoselectivity (anti/syn 87:13)15-17 with retention of the
enantiomeric purity (>96% ee) (Scheme 2). The stereochemical
outcome suggests that the allenylboronate [(S)-3h]18 was produced
with complete 1,3-chirality transfer with anti-stereochemistry and
that the propargylation of the aldehyde took place through a cyclic
transition state with complete Re-face selectivity with respect to
the allenylboronate reagent.17
Scheme 2. Synthesis and Lewis Acid Promoted Addition of Chiral
Allenylboronate (S)-3h
(7) There has been only one report for an R,γ,γ-trisubstituted allenylboron
compound with alkyl substituents that differ from each other. See: Carrie´,
D.; Carboni, B.; Vaultier, M. Tetrahedron Lett. 1995, 36, 8209–8212.
(8) Synthesis of axially chiral allenylboronates with moderate enantiomeric
purities has been reported (refs 3c and 4c). For allenylboranes with a chiral
auxiliary, see ref 3d.
(9) For Lewis acid mediated reactions of allylboronates with aldehydes, see:
(a) Ishiyama, T.; Ahiko, T.; Miyaura, N. J. Am. Chem. Soc. 2002, 124,
12414–12415. (b) Kennedy, J. W. J.; Hall, D. G. J. Am. Chem. Soc. 2002,
124, 11586–11587. (c) Hall, D. G. Synlett 2007, 1644–1655.
(10) The reaction of substrates that have acetoxy or methoxy leaving groups
instead of the carbonate resulted in lower yields even after longer reaction
times (acetoxy: 88%, 24 h; methoxy: 53%, 48 h).
(11) Directing effect of the phenyl group may have caused formation of a
ꢀ-borylation intermediate. See ref 6f.
(12) Low yields were due to the low reactivity of the di- and monosubstituted
substrates. Unreacted starting materials were recovered.
In summary, the Cu(O-t-Bu)/Xantphos system was identified to
be a catalyst for the regio- and stereoselective substitution of
propargylic carbonates with bis(pinacolato)diboron. Having toler-
ance toward different substitution patterns and functional groups,
the Cu-catalyzed reaction would serve as a useful method for the
synthesis of various allenylboronates. An axially chiral allenylbo-
ronate with unprecedented high enantiomeric purity was prepared
from an optically active propargylic carbonate. Synthetic utilities
of the allenylboronates have been demonstrated in their stereose-
lective addition to aldehydes.
(13) For the synthesis of homopropargylic alcohols with allenyltin, allenylzinc,
and allenylsilane reagents, see ref 1.
(14) Crude allenylboronates that were obtained by short-pass silica gel chro-
matography were used.
(15) In the absence of the external Lewis acid (BF3), the reaction of 1n with
benzaldehyde resulted in a lower yield of the product (4a) with a syn-
selectivity (0 °C, 44 h, 44%, anti/syn 16:84). The reaction of (S)-1h with
isobutyraldehyde without the Lewis acid catalyst afforded the product
((3S,4R)-4d) in a moderate yield (0 °C, 44 h, 61%) with a high enantiomeric
purity (97% ee for anti product) and a slightly lower anti-selectivity (anti/
syn 86:14) than that of the Lewis acid promoted reaction.
(16) In the case of 4a and 4d, methanol (5.0 equiv) was added in the aldehyde
addition. This slightly improved the syn/anti selectivities.
(17) The carbonyl additions of allenylmetal reagents bearing a Lewis acidic
metal group tend to favor production of anti-propargylic alcohols through
cyclic transition states. However, anomalous syn-preference in the addition
of allenyltitanium and allenylzinc reagents to benzaldehyde have been
reported. See: (a) Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.; Yamamoto,
H. Bull. Chem. Soc. Jpn. 1984, 57, 2768–2776. (b) Harada, T.; Katsuhira,
T.; Osada, A.; Iwazaki, K.; Maejima, K.; Oku, A. J. Am. Chem. Soc. 1996,
118, 11377–11390.
Acknowledgment. This work was supported by Grants-in-Aid
for Scientific Research on Priority Area ”Advanced Molecular
Transformations of Carbon Resources” from the Ministry of
Education, Culture, Sports, Science and Technology.
(18) Direct measurement of the enantiomeric purity of (S)-3h was unsuccessful
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
because of its instability.
JA806602H
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J. AM. CHEM. SOC. VOL. 130, NO. 47, 2008 15775