Asymmetric γ-methoxyallylation with the robust 10-tms-9- borabicyclo[3.3.2]decanes

Article abstract of DOI:10.1021/ol900865y

The asymmetric γ-methoxyallylboration of aldehydes with the configurationally very stable 1 gives nonracemic threo-β-methoxyhomoallylic alcohols 7 (65-93%) with excellent selectivity (96-99% de, 98-99% ee). The corresponding homoallylic amines 10 are obta

Full text of DOI:10.1021/ol900865y

ORGANIC
LETTERS
2009
Vol. 11, No. 12
2571-2574
Asymmetric γ-Methoxyallylation with the
Robust 10-TMS-9-Borabicyclo[3.3.2]decanes‡
Lorell Mun˜oz-Herna´ndez and John A. Soderquist*
Department of Chemistry, UniVersity of Puerto Rico, Rio Piedras,
Puerto Rico 00931-3346
jas@janice.uprr.pr
Received April 20, 2009
ABSTRACT
The asymmetric γ-methoxyallylboration of aldehydes with the configurationally very stable 1 gives nonracemic threo-ꢀ-methoxyhomoallylic
alcohols 7 (65-93%) with excellent selectivity (96-99% de, 98-99% ee). The corresponding homoallylic amines 10 are obtained from N-H
aldimines with similar efficiency (72-96%) and with excellent diastereoselectivity (98% de) but with lower enantioselectivity (56-86% ee).
These new reagents provide ready access to a Taxol side chain derivative.
Recent studies in our laboratories have revealed that the
robust 10-trimethylsilyl-9-borabicyclo[3.3.2]decane (10-
TMS-9-BBD) ring system provides a highly effective ste-
reocontrol element for many asymmetric organoborane
conversions.1,2 Embedded in this fascinating new chemistry
are many examples where sterically driven 1,3-borotropic
rearrangements can play a profound role in determining the
actual reagents produced and the products that result from
their reactions. These phenomena were particularly evident
in our new synthesis of 1,3-diols derived from 1,3-diboryl-
propenes, wherein the BBD substitution produces distinctly
different chemistry than has been observed from related
compounds with other boryl groups.2 Since these arrange-
ments can have stereochemical consequences upon the
reactions of interest, we chose to examine another important
organoborane conversion, namely, the Hoffmann γ-meth-
oxyallylboration of aldehydes, which leads to syn-1,2-diols.3
We felt that this process would benefit from the greater
selectivity of the 10-TMS-9-BBD systems versus the cor-
responding diisopinocampheylborane (Ipc2B) reagents, pro-
vided the derived reagents were configurationally stable
under their reaction conditions.
First reported by Hoffmann in 1981, the diastereoselective
addition of γ-methoxyallylboranes to aldehydes gave threo-
ꢀ-methoxyhomoallyl alcohols with good diastereoselectivity
(g96% de).3 An asymmetric variant to this process was later
reported by Brown4 using isomerically pure (Z)-(γ-meth-
oxyallyl)diisopinocampheylboranes. While it was observed
‡ This work is dedicated to Professor Dr. M. Frederick Hawthorne for
his revolutionary concepts and extraordinary contributions to boron chem-
istry.
(1) (a) Burgos, C. H.; Canales, E.; Matos, K.; Soderquist, J. A. J. Am.
Chem. Soc. 2005, 127, 8044. (b) Lai, C.; Soderquist, J. A. Org. Lett. 2005,
7, 799. (c) Herna´ndez, E.; Soderquist, J. A. Org. Lett. 2005, 7, 5397. (d)
Herna´ndez, E.; Canales, E.; Gonza´lez, E.; Soderquist, J. A. Pure Appl. Chem.
2006, 7, 1389. (e) Gonza´lez, A. Z.; Cana´les, E.; Soderquist, J. A. Org.
Lett. 2006, 8, 3331. (f) Canales, E.; Gonza´lez, A. Z.; Soderquist, J. A.
Angew. Chem., Int. Ed. 2007, 46, 397. (g) Gonza´lez, A. Z.; Soderquist,
J. A. Org. Lett. 2007, 9, 1081. (h) Roma´n, J. G.; Soderquist, J. A. J. Org.
Chem. 2007, 72, 9772. (i) Gonza´lez, A. Z.; Roma´n, J. G.; Gonza´lez, E.;
Martinez, J.; Medina, J. R.; Matos, K.; Soderquist, J. A. J. Am. Chem. Soc.
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401
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(3) Hoffmann, R. W.; Kemper, B. Tetrahedron Lett. 1981, 22, 5263.
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.
10.1021/ol900865y CCC: $40.75
Published on Web 05/22/2009
 2009 American Chemical Society

that these reagents are configurationally unstable above -78
°C, they add smoothly to aldehydes at this temperature to
provide the desired alcohols in g98% de and 88-92% ee.
Numerous synthetic applications for γ-methoxyallylboration
have been found for the synthesis of highly oxygenated
natural products.6 To assess the potential of BBD reagents
to enhance the value of this important process, it was decided
to prepare the (Z)-(γ-methoxyallyl)-10-TMS-9-BBD reagents
(1) and evaluate their behavior in the methoxyallylboration
of aldehydes and aldimines.
Scheme 1
Allyl methyl ether is metalated with sec-butyllithium in
THF at -78 °C (Scheme 1).7 The resulting cis-organolithium
reagent 3 is treated with either enantiomeric form of
B-methoxy-10-trimethylsilyl-9-BBD (4) at -78 °C, giving
the organoborate complex 5 that reacts with TMSCl to
generate 1 in 85% yield. Representative aldehydes were
added to 1 in THF at -78 °C to produce 6 (see Supporting
Information), which was treated with the appropriate pseu-
doephedrine to provide 8 and the threo-ꢀ-methoxyhomoallyl
alcohols 7 in 65-96% yield with excellent diastereoselec-
tivity (96-99%) and optical purity (98-99% ee). These
results are summarized in Table 1.
Table 1. Asymmetric γ-Methoxyallylboration of Representative
Aldehydes with 1
(5) Alexakis, A.; Furtos, J. C.; Mutti, S.; Mangeney, P. J. Org. Chem.
1994, 59, 3326.
7a
8
eeb
de
abs configc
(6) (a) Smith, A. L.; Pitsinos, E. N.; Hwang, C. K.; Mizuno, Y.; Saimoto,
H.; Scarlato, G. R.; Suzuki, T.; Nicolaou, K. C. J. Am. Chem. Soc. 1993,
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D.; Caggiano, L.; Panigada, L.; Sharon, O.; Costa, A. M.; Gennari, C.
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Castoldi, D.; Caggiano, L.; Panigada, L.; Sharon, O.; Costa, A. M.; Gennari,
C. Chem.sEur. J. 2006, 12, 51. (m) Yeung, K.-S.; Paterson, I. Chem. ReV.
2005, 105, 4237. (n) Lombardo, M.; Trombini, C. Chem. ReV. 2007, 107,
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Zhang, Q.; Lu, H.; Richard, C.; Curran, D. P. J. Am. Chem. Soc. 2004,
126, 36. (q) Curran, D. P.; Zhang, O.; Richard, C.; Lu, H.; Gudipati, V.;
Wilcox, C. S. J. Am. Chem. Soc. 2006, 128, 9561. (r) Nicolaou, K. C.;
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M. V. R. J. Org. Chem. 2005, 70, 2329. (t) Ramachandran, P. V.; Prabhudas,
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1
R
R
R
S
R
S
S
a, Me
b, Prd
c, i-Pr
d, Ph
e, t-Bu
65
93
65
90
89
80
61
53
71
76
50
50
98
98
98
99
98
98
98
98
98
99
98
96
S,S
S,S
R,R
S,S
R,R
R,R
f, CHdCHMe
a Yield was based on the amount of the aldehyde used. b Calculated
from the 31P NMR peak areas using the Alexakis method (see Figure 2).5
c The absolute configuration was determined by comparison of optical
rotation with literature values.3 d (3R,4R)-7b was prepared in 88% yield
(98% de and ee) from 1S.
For analysis purposes, the racemic reagent ((()-1) was
prepared to evaluate its thermal stability with respect to cis/
trans isomerization. In marked contrast to the instability of
the Ipc2B reagents, the pure cis geometry of 1 was retained
upon warming to room temperature. After either 4 d at 36
°C or 14 h at 80 °C, a ∼70:30 cis/trans mixture is formed.
Further heating at 80 °C or attempted vacuum distillation of
this mixture at 0.1 mmHg leads to decomposition without
significantly changing the cis/trans ratio.
Because of the unusual stability of these trialkylboranes, we
were able to obtain clear NMR spectral data for 1 as is illustrated
for the vinylic hydrogens in this mixture (Figure 1).
The clean resolution of the 31P NMR signals derived from
the isomeric Alexakis P-alkoxy-1,3,2-diazaphosphor-olane
derivatives of 7a can be seen in Figure 2. Thus, these esters
from 7a with another thermally isomerized cis/trans mixture
of (()-1 shows that this borane reagent gives rise to all four
of the possible isomeric products. However, the erythro
isomers are essentially absent (<1%) from the unisomerized
(()-1. Prepared from (10R)-1, (2S,3S)-7d is produced with
no detectable amount of the erythro (anti) diasteromers and
(7) Brown, H. C.; Lynch, G. J. J. Org. Chem. 1981, 46, 531.
2572
Org. Lett., Vol. 11, No. 12, 2009

It was of interest to determine the selectivity of 1 in its
additions to N-H aldimines. These substrates are generated
in situ from the methanolysis of the corresponding N-DIBAL
derivatives, which in turn are produced from the Isuno
hydroalumination of nitriles.8 Previous studies with the BBD
systems led us to expect lower selectivities for this process
than we had observed for aldehydes.9
The addition of N-DIBAL aldimines to 1 in THF solution
at -78 °C followed by MeOH (1 equiv) results in the clean
formation of 9 (11B NMR δ ∼51) (Scheme 2). An acidic
Scheme 2
Figure 1
.
Vinylic region of 1 after cis/trans isomerization.
workup provides the corresponding threo-ꢀ-methoxy ho-
moallylic amines 10 in 72-96% yield (98-99% de, 56-86%
ee) (Table 2). These selectivities are somewhat lower than
with γ-OMOM-allylB(Ipc)2 (cf. R ) Ph, 75%, 98% de, 86%
ee vs 65%, 98% de, 95% ee10 (86% ee)).12a
The synthesis of the side chain of Taxol (Figure 3) and
derivatives continues to be of interest due to the availability
Table 2. Asymmetric γ-Methoxyallylboration of Representative
Aldimines with 1
1
R
10 (%)a
eeb
dec
abs configd
R
S
S
R
R
a, Ph
b, 2-thienyl
c, c-Hx
d, p-MeOC6H4
e, Bn
75
96
78
72
77
86
56
72
84
80
98
98
98
98
98
S,S
S,R
R,R
S,S
S,S
a Isolated yield from acidic workup. b Calculated from the 31P NMR
peak areas using the Alexakis method (see Figure 2).5 c Determined by 1H
NMR analysis. d The absolute stereochemistry of 10d was assigned on the
basis of its conversion to the known methyl carbamate derivative.11 Others
were assigned on the basis of this and the known stereochemistry of 7.
of the baccatin III or 10-deacetylbaccatin III core unit (see
Figure 3, red portion) from the renewable leaves of Taxus
baccata.12
The simple synthesis of the Taxol side chain derivative
11 was accomplished from 10a (1S,2S) through benzoylation
followed by Sharpless oxidation13 in 70% overall yield
(Figure 3).
Figure 2
.
31P NMR spectra of the unpurified Alexakis esters of 7d
derived from cis/trans-(()-1 (top), cis-(()-1 (middle, peak area δ
146.2 vs 145.0 is >99:1), and cis-(10R)-1 (bottom, peak area δ 133.3
vs 146.2 is >99.5:0.5. Also see Supporting Information.
(8) Itsuno, S.; Wantanabe, K.; Kroda, S.; Yokoi, A.; Ito, K.; Itsuno, S.
J. Organomet. Chem. 1999, 581, 103.
<0.5% of (2R,3R)-7d. These results reveal that 1 exhibits
higher enantioselectivity in its addition to aldehydes than
the corresponding (Ipc)2B reagents (∼90% ee).3
(9) Herna´ndez, E.; Canales, E.; Gonza´lez, E.; Soderquist, J. A. Pure
Appl. Chem. 2006, 7, 1389.
Org. Lett., Vol. 11, No. 12, 2009
2573

Figure 4. MM-generated preferred pretransition state model (12a)
for the γ-methoxyallylboration of MeCHO with 1 (d(C*-C*) )
3.5 Å.
the BBD ring. Sarotti and Pellegrinet16 recently performed
B3LYP/6-31G*-level calculations on the transition state
energies for the allylboration of aldehydes and ketones with
the BBD reagents. The 10-R substitution was found to
provide a sterically based preference for the chairlike
transition state with cis, anti down geometry that was
consistent with our simple models (cf. 12a). The N-H
aldimines are less selective than are aldehydes because the
NH is larger than O and thus closer in size to the R-sp3 allylic
carbon atom. This narrows the energetic difference between
the cis versus trans adducts relative to the 10-TMS group,
resulting in lower selectivity.
In summary, the new B-(Z-γ-methoxyallyl)-10-TMS-9-
BBD reagents 1 add smoothly to aldehydes and N-H
aldimines to provide the corresponding syn-ꢀ-methoxy
homoallylic alcohols (65-93%) and amines (72-96%),
respectively. Because the reagents 1 are configurationally
stable, the process is highly diastereoselective (99% syn).
The enantioselectivity of 1 is higher for aldehydes (96-99%
ee) than for aldimines (56-86% ee). The amino alcohol 10a
was readily converted to the Taxol side chain derivative 11.
Figure 3. Synthesis of a side chain derivative of Taxol.
The absolute configuration of the amines was determined
by comparison of the sign of the optical rotation to that of
a precursor to (-)-4-epi-cytoxazone.14 This carbamate deri-
vative was prepared from 10d and MeOCOCl/TEA in
CH2Cl2 in 82% yield. The optical rotation confirmed the
(1S,2S) configuration of 10d.15
In our previous studies,1 we developed working models
for the origin of the enantioselectivities observed with the
BBD reagents that were based upon the relative energies of
the eight diastereomeric pretransition state complexes. As
shown in Figure 4 (12a), the most stable B-chiral complex
positions the carbonyl oxygen atom cis to the TMS group
in an anti aldehyde-1 adduct that is down with respect to
(10) (a) Ramachandran, P. V.; Burghardt, T. E. Chem. Eur. J. 2005,
11, 4387. (b) Ramachandran, P. V.; Burghardt, T. E.; Bland-Berry, L. J.
Org. Chem. 2005, 70, 7911.
(11) Kim, I. S.; Kim, J. D.; Ryu, C. B.; Zee, O. P.; Jung, Y. H.
Tetrahedron 2006, 62, 9349.
(12) (a) Li, F.; Li, Z.-M.; Yang, H.; Ja¨ger, V. Z. Naturforsch. 2008,
63b, 431. (b) Tosaki, S.; Tsuji, R.; Ohshima, T.; Shibasaki, M. J. Am. Chem.
Soc. 2005, 127, 2147. (c) Wang, Y.; He, Q.-F.; Wang, H.-W.; Zhou, X.;
Huang, Z.-Y.; Qin, Y. J. Org. Chem. 2006, 71, 1588. (d) Kudyba, I.; Raczko,
J.; Jurczak, J. J. Org. Chem. 2004, 69, 2844. (e) Juhl, K.; Jorgensen, K. A.
J. Am. Chem. Soc. 2002, 124, 2420. (f) Aggarwal, V. K.; Vasse, J. L. Org.
Lett. 2003, 5, 3987. (g) Baloglu, E. MS Thesis, Virginia Polytechnic Institute
and State University, 1998.
Acknowledgment. The support of the NSF (CHE-
0848192) is gratefully acknowledged.
Supporting Information Available: Full experimental
procedures, characterization data, selected spectra for 1, 4,
6-8, 10-11 and derivatives. This material is available free
of charge via the Internet at http://pubs.acs.org.
(13) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J.
Org. Chem. 1981, 46, 3936. See also refs 1j, 10a, and 11.
(14) Kim, I. S.; Kim, J. D.; Ryu, C. B.; Zee, O. P.; Jung, Y. H.
Tetrahedron 2006, 62, 9349.
OL900865Y
(15) In ref 14 the structures are correct, but there are errors in the
compound naming that can be confusing.
(16) Sarotti, A. M.; Pellegrinet, S. C. J. Org. Chem. 2009, 74, 3562.
2574
Org. Lett., Vol. 11, No. 12, 2009