Construction of homoallylic alcohols from terminal alkynes and aldehydes with installation of syn-stereochemistry

Article abstract of DOI:10.1021/ja502169d

A cationic rhodium(I) catalyst turns 2-silyl-1-alkenylboronate, readily prepared from a terminal alkyne, into the corresponding allylboronate species, which immediately undergoes nucleophilic addition to an aldehyde to give a syn-homoallylic alcohol stereoselectively.

Full text of DOI:10.1021/ja502169d

Communication
pubs.acs.org/JACS
Construction of Homoallylic Alcohols from Terminal Alkynes and
Aldehydes with Installation of syn-Stereochemistry
Tomoya Miura,* Yui Nishida, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510, Japan
S
* Supporting Information
ABSTRACT: A cationic rhodium(I) catalyst turns 2-silyl-
1-alkenylboronate, readily prepared from a terminal
alkyne, into the corresponding allylboronate species,
which immediately undergoes nucleophilic addition to an
aldehyde to give a syn-homoallylic alcohol stereoselec-
Then, an allylation reaction of aldehydes with (Z)-3a was
tively.
examined. A mixture of (Z)-3a and 4a in 1,2-dichloroethane
(DCE) was heated at 90 °C for 21 h in the presence of a
cationic rhodium(I) catalyst10 generated in situ from [Rh-
(nbd)(MeCN)2]SbF6 and dppm.11 Chromatographic purifica-
tion of the reaction mixture furnished syn-homoallylic alcohol
5aa in 97% isolated yield with excellent syn selectivity (eq 2).
tereoselective construction of contiguous chiral centers in
an acyclic system has been an area of intensive research in
S
organic synthesis. An allylation reaction of carbonyl compounds
with allylmetal reagents serves as a powerful tool for
stereoselective synthesis of homoallylic alcohols.1−3 When a
six-membered chairlike transition state is assumed, the
stereochemical outcome depends on the E/Z stereochemistry
of allylmetal reagents.4 Thus, the development of stereo-
selective preparative methods of allylmetal reagents has
attracted considerable attention.5 Recently, we have reported
a convenient method for the diastereoselective synthesis of anti-
homoallylic alcohols using simple 1-alkenylboronates,6 which
are readily prepared by hydroboration of terminal alkynes.
Cationic rhodium(I) or iridium(I) complexes catalyze their
double bond transposition to generate thermodynamically less
stable (E)-2-alkenylboronates,7 which spontaneously react with
coexisting aldehydes. Although this transformation makes anti-
homoallylic alcohols accessible from terminal alkynes and
aldehydes, in greater demand is a complementary stereo-
selective method for syn-diastereomers, which are generally
more difficult to synthesize.8 Cheng,8a Knochel,8b and Krische8f
made use of the presence of a sterically demanding silyl group
at the 2-position of allylic systems to gain syn stereochemistry.
We now report a new synthetic pathway starting from terminal
alkynes stereoselectively leading to syn-homoallylic alcohols via
2-silyl-1-alkenylboronates, which act as the synthetic equivalent
of (Z)-2-alkenylboronates (Figure 1).
1
No anti isomer was observed within the detection limit of H
NMR (>98:2).
When tetrabutylammonium fluoride (TBAF) was directly
added to the reaction mixture, protodesilylation of 5aa ensued
to form simple syn-crotylated product 6aa in 80% isolated yield
(eq 3).8f Thus, the reactions of eqs 1 and 3 are combined in
sequence to provide a stereoselective pathway to syn-
homoallylic alcohols starting from terminal alkynes and
aldehydes.
The following pathway consisting of two steps, i.e., double
bond transposition and allylation, accounts for the formation of
the homoallylic alcohol 5aa from (Z)-2-silyl-1-alkenylboronate
(Z)-3a and aldehyde 4a (eq 4). The rhodium(I) catalyst
promotes double bond transposition of (Z)-3a at 90 °C,
generating 2-silyl-2-alkenylboronate 7a,8a,12 which spontane-
ously adds to the aldehyde 4a through a six-membered chairlike
transition state at that temperature to produce 5aa. The syn
stereochemistry observed with 5aa suggests the stereoselective
generation of the E isomer of 7a.
(Z)-2-Silyl-1-butenylboronate (Z)-3a was prepared from but-
1-yne (1a) and PhMe2Si-Bpin (2) by silaboration under the
general conditions developed by Suginome and Ito (eq 1).9
Figure 1. Construction of syn-homoallylic alcohols starting from
terminal alkynes and aldehydes.
Received: March 3, 2014
Published: April 15, 2014
© 2014 American Chemical Society
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Journal of the American Chemical Society
Communication
allylation step proceeded without participation of the rhodium-
(I) catalyst.
Other 2-silyl-1-alkenylboronates 3 having a variety of R1
substituents were prepared from the corresponding terminal
alkynes also by the regio- and stereoselective silaboration
reaction9a and were subjected to the allylation reaction of 4a
(Table 1). As with the case of 3a (R1 = methyl), 2-silyl-1-
The control experiments were carried out to confirm this
mechanistic scenario; (Z)-2-silyl-1-alkenylboronate (Z)-3a was
treated with a catalytic amount of the rhodium(I) complex in
the absence of aldehyde 4a, and the double bond transposition
Table 1. Rh(I)-Catalyzed Reaction of (Z)-2-Silyl-1-
alkenylboronates (Z)-3b−j with 4-Chlorobenzaldehyde
1
was monitored by H NMR (eq 5). The E/Z ratio of the
a
(4a)
b
c
entry
3
R1
5
yield (%)
syn/anti
1
2
3
4
5
6
7
8
9
3b
3c
3d
3e
3f
Et
5ba
5ca
5da
5ea
5fa
92
99
83
>98:2
97:3
n-Bu
resulting 2-silyl-2-alkenylboronate 7a was constantly >98:2
during the early stage of transposition, suggesting that (E)-7a
was kinetically favored over (Z)-7a. After 3 h, the (E)-7a:3a
ratio became steady in favor of (E)-7a (ca. 97:3). Thus, unlike
the case of simple 1-alkenylboronates, (E)-7a is thermodynami-
cally far more stable than 3a. The steric repulsion between the
boryl group and other substituents in its vicinity would be
smallest with (E)-7a among the possible four isomers (E)/(Z)-
3a and (E)/(Z)-7a. This unidirectional double bond trans-
position of 3a stands in marked contrast to the result of its
palladium-catalyzed isomerization reaction reported by Oh-
mura and Suginome.13
cyclopentyl
i-Pr
>98:2
>98:2
>98:2
>98:2
>98:2
97:3
d
95
Ph
96
96
98
98
99
3g
3h
3i
TBSO(CH2)3
BzO(CH2)3
BnO(CH2)3
(Phth)N(CH2)3
5ga
5ha
5ia
3j
5ja
>98:2
a
4a (0.10 mmol), (Z)-3 (0.15 mmol), [Rh(nbd)(MeCN)2]SbF6 (7.5
mol %), and dppm (7.5 mol %) in DCE (2 mL) at 90 °C for 21 h
unless otherwise noted. Isolated yields (average of two runs).
Determined by H NMR of desilylated products or 5. Using 3e
(0.30 mmol), [Rh(nbd)(MeCN)2]SbF6 (10 mol %), and dppm (10
mol %).
b
c
d
1
We propose a mechanism depicted in Scheme 1 for the
double bond transposition. It initiates with coordination of the
Scheme 1. Proposed Pathway for Double Bond
Transposition
alkenylboronates 3b−f having ethyl, butyl, cyclopentyl,
isopropyl, and phenyl groups all exhibited excellent diaster-
eoselectivities (≥97:3) to give the corresponding syn-adducts
5ba−fa in yields ranging from 83% to 99% (entries 1−5).
Functional groups such as siloxy, benzoyloxy, benzyloxy, and N-
phthalimidoyl groups were tolerated in the alkyl chain (entries
6−9). The products 5 were readily desilylated by treatment
with TBAF to afford the corresponding homoallylic alcohols 6.
The reaction was highly general also with respect to
aldehydes (Table 2). An electronically and sterically diverse
array of aromatic aldehydes 4b−f gave the homoallylic alcohols
5bb−bf in high yield with diastereoselectivities over 95:5
(entries 1−5). Of note was that not only aromatic aldehydes
but also aliphatic ones 4g−i successfully participated in the
reaction with (Z)-3b to exhibit excellent diastereoselectivities
(entries 6−8).
We finally carried out the two reactions, i.e., the silaboration
and the allylation, in sequence in one pot (Scheme 2). First,
terminal alkynes 1 (1.5−2.3 equiv) were treated with PhMe2Si-
Bpin (2, 1.5 equiv) in the presence of Pt(PPh3)4 (3.0 mol %) at
110 °C in toluene for 4 h.9a After the reaction mixture was
cooled, toluene and an excess amount of terminal alkynes 1
were removed under reduced pressure. Then, 4-chloro-
benzaldehyde (4a, 1.0 equiv), [Rh(nbd)(MeCN)2]SbF6,
dppm, and DCE were added to the residue, and the reaction
mixture was further stirred at 90 °C for 21 h. Chromatographic
purification afforded the corresponding homoallylic alcohols 5
in excellent yields and diastereoselectivities in both cases. This
one-pot procedure minimizes generation of waste solvents.
double bond of (Z)-3a to the cationic rhodium(I) center, which
is followed by oxidative addition of the allylic C−H bond. For
the resulting π-allyl hydridorhodium intermediate, A would be
more stable than B due to the repulsive influence of the silyl
group. Reductive elimination gives rise to (E)-7a, which is the
most energetically stable isomer (vide supra). Thus, we assume
that (E)-7a is favored by both kinetics and thermodynamics.
The isolated (E)-7a was reacted with the aldehyde 4a in the
absence of the rhodium(I) catalyst in DCE at 90 °C for 18 h
(eq 6). The syn-homoallylic alcohol 5aa was formed in 97%
isolated yield with a syn/anti ratio of >98:2 in agreement with
the reported result.8a This experiment suggested that the
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Journal of the American Chemical Society
Communication
as starting materials, which are among the most easily accessible
starting materials, even from commercial sources, presenting
better chances of application for various synthetic purposes.
Table 2. Allylation Reaction of Aldehyde 4b−i with (Z)-2-
a
Silyl-1-pentenylboronates (Z)-3b
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and spectral data for the new
compounds. This material is available free of charge via
Internet at http://pubs.acs.org.
b
c
entry
4
R2
5
yield (%)
syn/anti
1
2
3
4
5
6
7
8
4b
4c
4d
4e
4f
Ph
5bb
5bc
5bd
5be
5bf
99
99
87
89
95
72
79
80
>98:2
>95:5
96:4
4-MeO2CC6H4
4-MeC(O)C6H4
3-MeOC6H4
2-MeC6H4
i-Bu
AUTHOR INFORMATION
Corresponding Authors
tmiura@sbchem.kyoto-u.ac.jp
murakami@sbchem.kyoto-u.ac.jp
■
>98:2
>98:2
97:3
4g
4h
4i
5bg
5bh
5bi
PhCH2CH2
Cy
>98:2
>98:2
Notes
The authors declare no competing financial interest.
a
4 (0.10 mmol), (Z)-3b (0.15 mmol), [Rh(nbd)(MeCN)2]SbF6 (7.5
mol %), and dppm (7.5 mol %) in DCE (2 mL) at 90 °C for 21 h.
Isolated yields (average of two runs). Determined by H NMR of
ACKNOWLEDGMENTS
b
c
1
■
This paper is dedicated to Honorary Professor Jiro Tsuji
(Tokyo Institute of Technology) in celebration of his 88th
birthday (Beiju). This work was supported by MEXT (Grant-
in-Aid for Scientific Research on Innovative Areas Nos.
22105005 and 24106718, Young Scientists (A) No.
23685019, Scientific Research (B) No. 23350041) and JST
(ACT-C).
desilylated products or 5.
Scheme 2. A One-Pot Reaction via Silaboration/Double
Bond Transposition/Allylation Reaction
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