Stereoselective synthesis of γ-substituted (Z)-allylic boranes via kinetically controlled hydroboration of allenes with 10-TMS-9-borabicyclo[3.3.2] decane

Article abstract of DOI:10.1021/ja905494c

(Chemical Equation Presented) Kinetically controlled hydroboration of allenes 8 and 14a-d with the readily accessible Soderquist borane 7, which is generated in situ from borohydride 6, constitutes a convenient and preparatively useful method for synthesi

Full text of DOI:10.1021/ja905494c

Published on Web 09/23/2009
Stereoselective Synthesis of γ-Substituted (Z)-Allylic Boranes via Kinetically
Controlled Hydroboration of Allenes with 10-TMS-9-borabicyclo[3.3.2]decane
Jeremy Kister, Amy C. DeBaillie, Ricardo Lira, and William R. Roush*
Department of Chemistry, Scripps Florida, Jupiter, Florida 33458
Received July 3, 2009; E-mail: roush@scripps.edu
The hydroboration of allenes is a potentially useful but relatively
undeveloped method for synthesis of allylic boranes.1-7 The hydrobo-
ration of monosubstituted allenes with di(isopinocampheyl)borane
[(Ipc)2BH] generally gives (E)-allylic boranes 4 with excellent
selectivity.3,4,8 It is inferred, based on work by Wang who studied the
hydroborations of 1-alkyl-1-trimethylsilylallenes with 9-BBN and
dicyclohexylborane,5,6 that the hydroboration of allenes 1 with
(Ipc)2BH proceeds via thermodynamically controlled isomerization4,9
of the kinetically formed (Z)-allylic borane 2 by way of the methal-
lylborane isomer 3 (Figure 1).10-12 Thus, allene hydroboration has
not proven useful8 for synthesis of 2 owing to the facile 1,3-
isomerization of 2 leading to 4 (Figure 1).4,9,13,14
temperature from 20 to 0 °C led to a significant improvement in the
reaction diastereoselectivity (87:13 favoring 11a, entry 2). The optimal
balance between product yield and diastereoselectivity was obtained by
performing the allene hydroboration at -10 °C for 5 h (75% yield, 11a:
12a ) 91:9, entry 3). Reducing the reaction time resulted in lower yields
due to incomplete hydroboration. Yet, increasing the reaction time to 12 h
at -10 °C led to a reduced 11a:12a ratio (entry 4), likely due to allylborane
1,3-isomerization under these conditions. Further reduction of the hy-
droboration temperature resulted in lower conversion, but with consistent
92: 8 d.s., which presumably reflects the kinetic selectivity for hydrobo-
ration via the two, nonequivalent faces of allene 8 (entries 5,6).22
Table 1. Optimization of the Hydroboration of 8 Using Borane 7
Figure 1. Synthesis of (E)-allylic boranes via allene hydroboration.
In connection with an ongoing research problem, we needed to develop
a stereocontrolled synthesis of 2 [R ) B(OR′)2] and explored the
hydroboration of 1 [R ) B(OR′)2] with (Ipc)2BH. Because attempts to
suppress the 1,3-allylic isomerization of 2 [R ) B(OR′)2] by performing
the hydroboration of 1 with (Ipc)2BH even at -78 °C in the presence of
transition metal catalysts15 were unsuccessful,16 we sought to identify a
chiral dialkylborane that would hydroborate allenes 1 with high (Z)-
stereoselectivity but without competitive 1,3-isomerization of the initially
formed (Z)-allylic borane 2. Based on the unusual thermal isomeric stability
of (E)- and (Z)-crotyl-10-TMS-9-borabicyclo[3.3.2]decane reagents,17,18
we targeted the use of and report herein that 10-TMS-9-bora-
bicyclo[3.3.2]decane 719,20 is highly effective as a reagent for kinetically
controlled allene hydroboration leading to 2.10 Importantly, the Soderquist
borane 7 has enabled us to synthesize several (Z)-allylboranes that are
inaccessible by alternative synthetic methods.1
Nonracemic borane 7 [10-TMS-9-BBD-H] is easily prepared from
pseudoephedrine complex 5 by using Soderquist’s procedure (Scheme
1).19,20 Both enantiomers of 5 are commercially available but also are
easily prepared in two steps from B-OMe-9-BBN.17 We found,
however, that generation of 7 from ate complex 6 is best performed
in the presence of the allene, owing to the instability of 7.21
hydroboration conditions
d.s.
11a:12ab
entry
temp (°C)
time (h)
% yielda
1
2
3
4
5
6
20
0
2
2
66
69
51:49
87:13
91:9
84:16
92:8
-10
-10
-20
-30
5
75 (95% e.e.)c
12
12
12
63
66
36
92:8
a Isolated yields of 11a-12a. b Diastereomer ratios were determined by
1H NMR analysis. c Determined by Mosher ester analysis.23
By using the optimized conditions of entry 3 (Table 1), a variety of
syn-diols were prepared with g90:10 d.s. in 71-77% yields and
95-96% e.e. from the allylborations of (Z)-γ-borylallylborane 9 with
other representative aldehydes (see SI). However, our main reason for
developing the hydroboration of 8 with the Soderquist borane 7 was
to use the derived 9 in double allylboration reactions. As summarized
in Scheme 2 (see also SI for the t.s.), a variety of (Z)-1,5-anti-diols 13
were obtained in 67-86% yield with g92:8 d.s. and in 94-96% e.e.
1,5-anti-Diols 13 are inaccessible by using our previously published,
first generation double allylboration sequence.12
Scheme 1. Synthesis of Borane 7
Additional examples of (Z)-γ-substituted allylboranes generated via
allene hydroboration are provided in Table 2. Hydroboration of pheny-
lallene (14a) with in situ generated 7 provided a solution of 15a which
was treated with aldehydes at -40 °C to give syn-homoallylic alcohols
16a and 16b with g93:7 d.s. and 92-93% e.e. (entries 1, 2). In contrast,
hydroboration of 14a with (Ipc)2BH provides the (E)-allylic borane, which
in turn provides the anti-homoallylic alcohol epimer of 16.4 Similarly,
Conditions for the kinetically controlled allene hydroboration were
optimized by using 8 as the substrate; stereoselectivity was assessed by
subjecting the derived allylboranes to an allylboration-oxidation sequence3
with benzaldehyde (Table 1). A 1:1 mixture of syn-1,2-diol 11a and the
1,2-anti diastereomer 12a was obtained when the hydroboration of 8 was
performed at 20 °C for 2 h (entry 1). Decreasing the hydroboration
9
14174 J. AM. CHEM. SOC. 2009, 131, 14174–14175
10.1021/ja905494c CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Enantioselective Synthesis of (Z)-1,5-Diols 13
reactions summarized in Scheme 2 and Table 2 were performed under
conditions that minimize allylborane isomerization and presumably
reflect kinetic selectivity for hydroboration of the two diastereotopic
faces of the allene substrates.22 Several additional experiments were
performed with alkyl-substituted allenes 14d-14f to probe the limits
of the hydroboration selectivity. Whereas the hydroboration of tert-
butyl substituted 14d proceeded with g99:1 kinetic selectivity (Table
2 entry 7), selectivity dropped to ca. 78:22 for the hydroboration of
cyclohexyl substituted 14e (entry 8) and eroded to 60:40 with the less
sterically demanding alkyl substituted allene 14f (entry 9). The syn/
anti selectivity in these cases is largely independent of hydroboration
temperature (see SI), indicating that the modest to poor (Z)-selectivity
with 14e and 14f is due to the ability of 7 to hydroborate the allenes
syn to moderately sterically demanding alkyl groups.
In summary, kinetically controlled hydroboration of monosubstituted
allenes 8 and 14a-d with the readily accessible Soderquist borane 7
constitutes a convenient, selective (g9:1), and preparatively useful
method for synthesis of (Z)-γ-(substituted)allylboranes 9 and 15a-d.
These reagents, which undergo allylborations of aldehydes with
typically 89-96% e.e., are representative of (Z)-allylic boranes that
are inaccessible, or accessible only with great difficulty,24 by alternative
methods. This work also defines the opportunities for selective, kinetic
hydroboration of monosubstituted allenes. Applications of this meth-
odology in natural products synthesis are currently under investigation
and will be reported in due course.
kinetically controlled hydroboration of phenyldimethylsilylallene (14b)
followed by treatment of the in situ generated (Z)-γ-silylallylborane 15b
with representative aldehydes provided the syn-ꢀ-hydroxyallylsilanes 17a
and 17b with 9:1 d.s. and 86-89% e.e. (entries 3, 4). We have previously
documented the challenges associated with synthesis of (Z)-γ-silylallylbo-
ranes, and the present route constitutes a significant improvement.24
Tributylstannylallene (14c) also proved to be an excellent substrate for
hydroboration with in situ generated 7 (entries 5,6). The resulting
ꢀ-hydroxyallylstannanes 18a,b are very sensitive to Peterson-type elimina-
tion during attempted chromatographic purification, or during attempts to
functionalize the hydroxyl group. Therefore, the enantiomeric purity of
18 was assessed at the stage of 1,5-diol 20 following the BF3-OEt2
promoted reaction of predecessor borinate 19 with aldehydes at -78 °C
(see SI). As with (Z)-allylborane 9, 15c readily isomerizes to the (E)-γ-
stannylallylborane isomer at ambient temperature and therefore must be
used immediately after the allene hydroboration step.
Acknowledgment. This work was supported by the NIH
(GM038436 and GM026782) and a fellowship to J.K. from the
Ministe`re des Affaires Etrange`res et Europe´ennes (France).
Supporting Information Available: Experimental procedures and
spectroscopic data for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
References
These examples provide clear evidence that the hydroboration of
allenes 8 and 14a-c with borane 7 provides (Z)-γ-substituted
allylboranes 9 and 15a-c as the kinetic product. All of the allylboration
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entry
R1
R2
product
% yielda
syn/antib
% e.e.c
1d f h
Ph
Ph
Ph
16a
16b
17a
17b
18a
18b
21
74
60
79
94:6
93:7
90:10
90:10
88:12
91:9
99:1
78:22
60:40
93
92
86
89
93k
94l
93
98
98
, ,
2d f h
Ph(CH2)2
Ph
Ph(CH2)2
Ph
Ph(CH2)2
Ph
, ,
(17) Burgos, C. H.; Canales, E.; Matos, K.; Soderquist, J. A. J. Am. Chem. Soc.
2005, 127, 8044.
3d f i
SiMe2Ph
SiMe2Ph
SnBu3
SnBu3
t-Bu
, ,
(18) Mun˜oz-Herna´ndez, L.; Soderquist, J. A. Org. Lett. 2009, 11, 2571.
(19) Soderquist, J. A.; Matos, K.; Burgos, C. H.; Lai, C.; Vaquer, J.; Medina,
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references cited therein.
4d f i
71
, ,
5e g h
g66j
g67j
70
,
,
6e g h
,
,
7m f h
, ,
8m g h
c-C6H11
n-C8H17
Ph
Ph
22
23
86n
81n
,
,
(21) Racemic 7 appears to be much more stable in solution than enantiomerically
pure 7 and can be generated from 6 in the absence of allene. The difference
in stabilty of racemic vs enantiomerically pure 7 presumably relates to
differences in their monomer-dimer equilibria.
9m g h
,
,
a Isolated yields of the indicated product, unless noted otherwise.
b
1
(22) This conclusion depends on the assumption that the aldehyde allylboration
proceeds with high fidelity via the usual chairlike t.s.
Diastereomer ratios for 16-18 and 21-23 were determined by H NMR
analysis of crude reaction mixtures. c Determined by the Mosher method.23
d Hydroboration: 0 °C/12 h. e Hydroboration: -10 °C/5 h. f Allylboration:
-40 °C/12 h. g Allylboration: -78 °C/4 h. h Workup: ethanolamine.
i Workup: pH 7 buffer (KH2PO4/NaOH). j Isolated yield of 20 from 14c.
k % e.e. of 20a. l % e.e. of 20b. m Hydroboration: 0 °C/2-6 h. n Combined
yield, syn/anti mixture.
(23) (a) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512. (b) Dale,
J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512.
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Org. Lett. 2005, 7, 4245. (b) Lira, R.; Roush, W. R. Org. Lett. 2007, 9,
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