stoichiometric propargyl intermediate or a specific sub-
stitution pattern on the reagent for transition metal-
catalyzed processes. Herein, we report an operationally
simpleand general zinc-catalyzed allenylation ofaldehydes
and ketones with an allenyl boronate.
Table 1. Optimization of the Zinc Catalyzed Allenylation
Additions to carbonyl species with allenyl zinc reagents
is a prominent approach for the preparation of homopro-
pargylic alcohols.3,12 This site selectivity is generally ratio-
nalized by a rapid equilibration between propargyl and
allenyl zinc intermediates wherein both the allenyl zinc
entry conditionsa
solvent
temp (°C) 4a:5ab
convc
0.5%
1
None
THF
20
20
2
None
Toluene
THF
1%
3
7% Et2Zn
20
20
20
20
20
20
20
20
ꢀ20
ꢀ10
0
30:70
100%
Scheme 1. Typical Site Selectivity for the Preference of Propar-
gylation with Propargyl/Allenyl Zinc Reagents
4
20% Et2Zn THF
25:7516 100%d
5
7% Et2Zn
7% Et2Zn
7% Et2Zn
7% Et2Zn
2% Et2Zn
Heptane
92:8
100%
100%
100%
100%
100%
100%
44%
6
DCM
84:16
71:29
93:7
7
IpAc
8
Toluene
Toluene
9
93:7
10
11
12
13
14
15
13% Et2Zn Toluene
54:46
97:3
7% Et2Zn
7% Et2Zn
7% Et2Zn
7% Et2Zn
5% Et2Zn
Toluene
Toluene
Toluene
Toluene
Toluene
96:4
100%
100%
100%
100%e
95:5
40
0
85:15
93:7
a Diethyl zinc (mol % to starting aldehyde) was charged to an
anhydrous solution of the aldehyde and borolane 6 (1.5 equiv) in the
indicated solvent at the indicated temperature. b Site selectivity between
4a:5a determined by HPLC. c Molar conversion based on aldehyde.
d Seventy-four percent isolated yield for 5a. e Ninety-two percent iso-
lated yield for 4a.
intermediate and propargylation pathway is favored
(Scheme 1).2,13 The few cases wherein a zinc-mediated
addition proceeded with selectivity for allenylation are
exclusively related to a specific substitution pattern on
the allenyl/propargyl zinc moiety that favors allenylations
wherein propargylation is favored when an unsubstituted
allenyl/propargyl zinc intermediate is utilized.7b,14 Our
zinc-catalyzed propargylation of aldehydes and ketones
with both propargyl and allenyl boronates was based on
these principles and a facile B/Zn exchange.15
When the zinc-catalyzed addition with an allenyl boro-
nate to an aldehyde was examined under different condi-
tions, a mixture of the allenylic and homopropargylic
alcohols was observed (Table 1). More importantly, either
isomer can be favored based predominately on the solvent
and catalyst loadings. With 7 mol % diethyl zinc and
the model p-anisaldehyde, the solvent tetrahydrofuran
favored the homopropargylic alcohol product and toluene
favored the allenyl alcohol. In toluene, low catalyst load-
ings (7 mol %) favored the allenyl alcohol (93:7) whereas
high loadings (100 mol %) favored the homopropargylic
alcohol (86:14) (Figure 1). At approximately 15 mol %
diethyl zinc, a nearly equal ratio of the homopropargyl and
allenyl alcohol can be obtained. The temperature showed a
minimal effect on the site selectivity, and the optimal
conditions to afford the allenyl alcohol utilized 5 mol %
diethyl zinc in toluene at 0 οC.
The optimized conditions for the zinc-catalyzed alleny-
lation with an allenyl borolane proved general for a broad
number and types of aldehydes and ketones (Table 2). The
methodology afforded >90:10 site selectivity for the al-
lenylic alcohol for both aldehydes and ketones and gen-
erally provided high yields. Numerous functional groups
were also tolerated including aryl and aliphatic halides,
esters, olefins, and Lewis basic functional groups such as
quinolines and carbamates that are typically not compa-
tible with Lewis acid-catalyzed processes. Furthermore,
the more electrophilic aldehydes provided higher prefer-
ence (99:1) for the allenylic alcohol (entries 2ꢀ4) in com-
parison to the electron-rich p-anisaldehyde (93:7) (entry 1).
(12) For selected examples, see: (a) Marshall, J. A.; Adams, N. D.
Org. Lett. 2000, 2, 2897–2900. (b) Marshall, J. A.; Yanik, M. M. J. Org.
Chem. 2001, 66, 1373–1379. (c) Marino, J. P.; McClure, M. S.; Holub,
D. P.; Comasseto, J. V.; Tucci, F. C. J. Am. Chem. Soc. 2002, 124, 1664–
1668. (d) Bahadoor, A. B.; Flyer, A.; Micalizio, G. C. J. Am. Chem. Soc.
2005, 127, 3694–3695. (e) Marshall, J. A. J. Org. Chem. 2007, 72, 8153–
8166. (f) Poisson, J.-F.; Normant, J. F. Org. Lett. 2001, 3, 1889–1891.
(g) Chemla, F.; Ferreira, F.; Gaucher, X.; Palais, L. Synthesis 2007,
1235–1241. (h) Ma, X.; Wang, J.-X.; Li, S.; Wang, K.-H.; Huang, D.
Tetrahedron 2009, 65, 8683–8689.
(13) (a) Ma, S.-M.; Zhang, A.-B. Pure Appl. Chem. 2001, 73, 337–341.
(b) Marshall, J. A. Synthesis and Reactions of Allenylzinc Reagents. In
The Chemistry of Organozinc Compounds; Rappoport, Z., Marek, I., Eds.;
John Wiley & Sons Ltd: England, 2006; Ch 10. (c) Zweifel, G.; Hahn, G.
J. Org. Chem. 1984, 49, 4565–4567. (d) Poisson, J.-F.; Normant, J. F.
J. Org. Chem. 2000, 65, 6553–6560. (e) Harada, T.; Katsuhira, T.; Osada,
A.; Iwazaki, K.; Maejima, K.; Oku, A. J. Am. Chem. Soc. 1996, 118,
11377–11390.
(16) The site selectivity for propargylation is dependant on the
addition order and workup conditions. An 80:20 selectivity favoring
propargylation with a 78% isolated yield for the alkyne 5a can be
obtained when the aldehyde is charged to a solution of the borolane
6 and diethyl zinc in THF. See Supporting Information for reaction
details.
(14) Jogi, A.; Maeorg, U. Molecules 2001, 6, 964–968.
(15) Fandrick, D. R.; Fandrick, K. R.; Reeves, J. T.; Tan, Z.;
Johnson, C. S.; Lee, H.; Song, J. J.; Yee, N. K.; Senanayake, C. H.
Org. Lett. 2010, 12, 88–91.
Org. Lett., Vol. 13, No. 20, 2011
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