First Meerwein-Ponndorf-Verley alkynylation: Nonorganometallic way for carbonyl alkylations [16]

Full text of DOI:10.1021/ja9821347

10790
J. Am. Chem. Soc. 1998, 120, 10790-10791
Scheme 1
First Meerwein-Ponndorf-Verley Alkynylation:
Nonorganometallic Way for Carbonyl Alkylations
Takashi Ooi, Tomoya Miura, and Keiji Maruoka*
Department of Chemistry
Graduate School of Science
Hokkaido UniVersity
Sapporo 060-0810, Japan
case, the use of 3 equiv of propargylic alcohol 1 provided a
synthetically useful level of chemical yield (entry 5).
ReceiVed June 19, 1998
Undoubtedly the Meerwein-Ponndorf-Verley (MPV) reduc-
tion is one of the most classical, yet important organic
transformations.1-3 Advantages of the MPV reduction include
its chemoselectivity, mild reaction conditions, operational simplic-
ity, safe handling, and ready adaptation both in the laboratory
and on a large scale.4 This reaction is applicable to various
carbonyl substrates with aluminum alkoxides, generally Al(OPri)3
as the catalyst and i-PrOH as the hydride source, as shown in
[A].5 However, the corresponding alkylation, i.e., MPV alkyla-
Other selected examples are listed in Table 1. The requisite
(propargyloxy)aluminum reagents 6 are readily accessible from
either (1) (o,o′-biphenylenedioxy)methylaluminum (5a) and the
corresponding propargylic alcohols 4 or (2) (o,o′-biphenylene-
dioxy)(t-butoxy)aluminum (5b) and 4 by the ligand exchange.
The second preparative method works equally well (entries 6,
11, and 21). In general, a series of the reactive aldehydes,
2-haloaldehydes, 2,2′-dihaloaldehydes, chloral, bromal, and pen-
tafluorobenzaldehyde can be transformed to the corresponding
secondary propargylic alcohols 8 under the MPV alkynylation
conditions using stoichiometric 6 (R ) Ph, CHdCHPh).9 Acetyl-
enic aldehyde can be also alkynylated under similar reaction
conditions (entry 25).10 In certain cases, the alkynylation proceeds
under catalytic conditions (entries 3, 12, and 22). Since the MPV
reaction is reversible, the overall efficiency is subtly influenced
by the steric and electronic properties of the aldehydic substrates
7 and alkynyl donors 4 as well as reaction conditions as shown
in Table 1.
tion, has never been realized mainly because of the inertness of
alkyl transfer [B] compared to the facile hydride transfer [A] in
the MPV reduction. We here report the first example of MPV
alkynylations for various aldehydes as illustrated in Scheme 1.
This truly represents a nonorganometallic way of effecting
carbonyl alkylation of aldehydes. The success of the present
approach relies heavily on the discovery of a ligand-accelerated
mode for the MPV alkynylations, which shows beneficial effect
on the rate of alkyl transfer.
A typical Al reagent, Al(OC(CH3)2CtCPh)3 for the MPV
alkynylation was prepared by treatment of propargylic alcohol 1
(3 equiv) in CH2Cl2 with a 1 M hexane solution of Me3Al (1
equiv) at room temperature for 30 min.6 When an equimolar
mixture of 2,2-dichlorodecanal (2)7,8 and the in situ generated
Al(OC(CH3)2CtCPh)3 was stirred at room temperature for 5 h,
acetylenic alcohol 3 was obtained in only a trace amount. The
choice of aluminum ligands is crucial in enhancing the rate of
alkynylation. When two phenoxy ligands were introduced to
prepare PhCtCC(CH3)2OAl(OPh)2 [derived from 1 and MeAl-
(OPh)2], the alcoholic product 3 was obtainable in higher yield
(16%) under otherwise identical conditions. Switching the two
phenoxy ligands to o-phenylenedioxy and o,o′-biphenylenedioxy
ligands, the alkynylation was further accelerated to give 3 in 20%
and 53% yields, respectively (entry 4 in Table 1). In the latter
One characteristic feature of the MPV alkynylation is the
chemoselective transfer of functionalized alkynyl groups to
aldehyde carbonyls. Indeed, reaction of chloral with function-
alized Al reagent 911 in CH2Cl2 proceeds nicely at room
temperature to furnish alcohol 10 in good yield, leaving the keto
(1) Meerwein, H.; Schmidt, R. Liebigs Ann. Chem. 1925, 444, 221.
(2) Verley, A. Bull. Soc. Chim. Fr. 1925, 37, 537.
(3) Ponndorf, W. Angew. Chem. 1926, 39, 138.
(4) De Graauw, C.; Peters, J.; Van Bekkum, H.; Huskens, J. Synthesis 1994,
1007.
(9) Attempted allylation of aldehyde 2 with 2-methyl-4-penten-2-ol and
5a under otherwise similar reaction conditions gave none of the desired
homoallylic alcohols, hence, excluding the possibility of the stabilized
carbocation mechanism in our system. We acknowledge the reviewer for a
valuable comment on this point. For a recent example of allyl-transfer reaction,
see: Nokami, J.; Yoshizane, K.; Matsuura, H.; Sumida, S. J. Am. Chem. Soc.
1998, 120, 6609.
(10) R,â-Acetylenic aldehydes can be synthesized from terminal alkynes
with high efficiency. Journet, M.; Cai, D.; DiMichele, L. M.; Larsen, R. D.
Tetrahedron Lett. 1998, 39, 6427.
(11) The functionalized propargylic alcohol was synthesized from 2-methyl-
3-butyn-2-ol in 40% yield as follows: (i) 1-bromo-4-iodobenzene, PdCl2(PPh3)2,
CuI, Et3N, CH2Cl2, room temperature. (ii) BuLi (2 equiv), ether, 0 °C.; then
pivaloyl chloride, -78 to -20 °C.
(5) Review: Wilds, A. L. Org. React. 1944, 2, 178.
(6) This Al reagent can also be generated from the ligand exchange of
Al(OPri)3 and 1 (3 equiv) in CH2Cl2 by the azeotropic removal of the in situ
generated i-PrOH.
(7) 2,2-Dichlorodecanal (2) was readily prepared from decanal according
to the literature procedure. See: Verhe, R.; Kimpe, N. D.; Buyck, L. D.;
Schamp, N. Synthesis 1975, 455.
(8) We chose 2,2-dihaloaldehydes as representative reactive aldehydes
because of the ease of further manipulation of the alkylation products by simple
dehalogenation. For the C-Cl bond cleavage, see: (a) Krishnamurthy, S.;
Brown, H. C. J. Org. Chem. 1980, 45, 849. (b) Pinder, A. R. Synthesis 1980,
425. (c) Noyori, R.; Hayakawa, Y. Org. React. 1983, 29, 163.
10.1021/ja9821347 CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/06/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 41, 1998 10791
Table 1. MPV Alkynylation of Various Aldehydesa
reaction time
(h)
product,
entry
aldehyde, 7
alkyl source 4 (equiv)
Al reagent, 5
8 % yieldb
1
2
R1 ) CHCl(CH2)7CH3
R ) Ph (3)
5a
2
1
40 (78:32)c
R ) CHdCHPh (3)
R ) CHdCHPh (3)
R ) Ph (1)
5a
80 (75:25)c
3
5a (10 mol %)
5
72 (76:24)c
53
4
R1 ) CCl2(CH2)7CH3
5a
5
5
R ) Ph (3)
R ) Ph (3)
5a
5
70
6
5b
5
61
7
R ) CHdCHPh (1)
R ) CHdCHPh (3)
R ) Ph (1)
5a
2
42
8
5a
2
66
9
R1 ) CCl3
5a
5
81
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
R ) Ph (3)
5a
5
97
R ) Ph (3)
5b
5
84
R ) Ph (3)
5a (20 mol %)
12
2
63
R ) CHdCHPh (1)
R ) CHdCHPh (2)
R ) Ph (1)
5a
85
5a
5
99
R1 ) CBr3
R1 ) C6F5
5a
5
52
R ) Ph (3)
5a
5
81
R ) CHdCHPh (1)
R ) CHdCHPh (3)
R ) Ph (1)
5a
2.5
2.5
5
58
5a
89
5a
67
R ) Ph (3)
5a
5
5
12
1.5
1.5
1
85
R ) Ph (3)
5b
75
R ) Ph (3)
5a (10 mol %)
51
R ) CHdCHPh (1)
R ) CHdCHPh (3)
R ) Ph (5)
5a
79
5a
99
R1 ) CtCPh
5ad
54e
a Unless otherwise noted, alcohol 4 was reacted with Al reagent 5 (1 equiv) in CH2Cl2 at room temperature for 30 min and then treated with
1
aldehyde 7 under the given reaction conditions. b Isolated yield. c erythro/threo Ratio of 8 (R ) Ph or CHdCHPh) was determined by H NMR
analysis. The relative configuration of these isomers was correlated, after hydrogenation to the corresponding saturated chlorohydrins, with that of
alkylation products of 2-chlorodecanal by the corresponding Grignard reagents. See: Morrison, J. D.; Mosher, H. S. Asymmetric Organic Reactions;
American Chemical Society: Washington, DC, 1976; p 99. d Use of 5 equiv of Al reagent. e The alkynylation product 8 (R ) Ph) works as a
hydride source for the MPV reduction of the starting aldehyde to furnish 1,5-diphenyl-1,4-pentadiyn-3-one (17%) as a side-reaction product.
In summary, we have successfully developed a MPV alkynyl-
ation procedure which is highly effective for the selective
alkynylation of aldehydes under mild conditions. The alkyny-
lation proceeds without organometallic reagent by taking advan-
tage of the push-pull effect of modified aluminum reagents. A
more appropriate choice of metals and a more sophisticated design
of the MPV alkylation system for general applicability are the
subjects of our ongoing study.
functionality intact. Such transformation is not easily realized
by the ordinary alkynylation procedures because of the difficulty
of generating functionalized alkynylmetal reagents.
The present approach is also applicable to the cyanation of
aldehydes with commercially available acetone cyanohydrin as
cyanide source. For example, treatment of 2,2-dichlorodecanal
(2) with acetone cyanohydrin under the influence of aluminum
reagent 5a or 5b afforded the corresponding cyanohydrin 11 in
high yield.
Acknowledgment. This work was supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Science, Sports and
Culture.
JA9821347