Chiral Synthesis via Organoboranes. 44. Racemic and Diastereo- and Enantioselective Homoallenylboration Using Dialkyl 2,3-Butadien-1-ylboronate Reagents. Another Novel Application of the Tandem Homologation-Allylboration Strategy

Article abstract of DOI:10.1021/jo9513976

A highly general and efficient racemic and diastereo- and enantioselective homoallenylboration has been achieved with a novel boron reagent, dialkyl 2,3-butadien-1-ylboronate (dialkyl homoallenylboronate).The starting isopropyl 2,3-butadien-1-ylboronate is prepared from allenylmagnesium bromide and diisopropyl (halomethyl)boronate.This β,γ-unsaturated boronate reagent reacts readily with aldehydes via usual allylic rearrangement to give the alkyl(1,3-butadien-2-yl)methanols in excellent yields.Among the solvents examined, toluene favored enhanced reaction rates.The reaction is relatively sensitive to steric effects, so that sterically hindered aldehydes react significantly slower.Generaly, the reactivities are moderately lower than those of the corresponding simple allylboronates, possibly due to the reduced HOMO electron density of the internal double bond.Also, the reagent exhibits a unique anti diastereoselectivity in reaction with α-chiral aldehydes in contrast to the syn selectivity observed with a corresponding organosilicon reagent.However, this anti selectivity is similar to that observed for the allylboration reactions.We have successfully extended this reaction to the first general synthesis of optically active alkyl(1,3-butadien-2-yl)methanol using chiral tartrate boronate reagents with diisopropyl tartrate (DIPT) and bis(2,4-dimethyl-3-pentyl) tartrate (DMPT) as the chiral modifiers.These reagents react with aldehydes even at -78 deg C, albeit slowly, and exhibit remarkable enantioselectivity with al classes of aldehydes examined with the exception of aromatic and α-alkoxy aldehydes.Again, while the selectivity parallels that of the corresponding allylboronate, the reactivities are lower.Also, the double asymmetric homoallenylboronation of 2,3-O-isopropylidene-D-glyceraldehyde using the DMPT modified boronate reagent gives an excellent 98.5percent anti selectivity in the matched case and a moderately lower value, 82percent syn selectivity, in the mismatched case.

Full text of DOI:10.1021/jo9513976

100
J . Org. Chem. 1996, 61, 100-104
Ch ir a l Syn th esis via Or ga n obor a n es. 44. Ra cem ic a n d Dia ster eo-
a n d En a n tioselective Hom oa llen ylbor a tion Usin g Dia lk yl
2,3-Bu ta d ien -1-ylbor on a te Rea gen ts. An oth er Novel Ap p lica tion of
th e Ta n d em Hom ologa tion -Allylbor a tion Str a tegy
Raman Soundararajan, Guisheng Li, and Herbert C. Brown*
H. C. Brown and R. B. Wetherill Laboratories of Chemistry, Purdue University,
West Lafayette, Indiana 47907
Received J uly 28, 1995X
A highly general and efficient racemic and diastereo- and enantioselective homoallenylboration
has been achieved with a novel boron reagent, dialkyl 2,3-butadien-1-ylboronate (dialkyl homoal-
lenylboronate). The starting diisopropyl 2,3-butadien-1-ylboronate is prepared from allenylmag-
nesium bromide and diisopropyl (halomethyl)boronate. This â,γ-unsaturated boronate reagent
reacts readily with aldehydes via the usual allylic rearrangement to give the alkyl(1,3-butadien-
2-yl)methanols in excellent yield. Among the solvents examined, toluene favored enhanced reaction
rates. The reaction is relatively sensitive to steric effects, so that sterically hindered aldehydes
react significantly slower. Generally, the reactivities are moderately lower than those of the
corresponding simple allylboronates, possibly due to the reduced HOMO electron density of the
internal double bond. Also, the reagent exhibits a unique anti diastereoselectivity in reaction with
R-chiral aldehydes in contrast to the syn selectivity observed with a corresponding organosilicon
reagent. However, this anti selectivity is similar to that observed for the allylboration reactions.
We have successfully extended this reaction to the first general synthesis of optically active alkyl-
(1,3-butadien-2-yl)methanols using chiral tartrate boronate reagents with diisopropyl tartrate (DIPT)
and bis(2,4-dimethyl-3-pentyl) tartrate (DMPT) as the chiral modifiers. These reagents react with
aldehydes even at -78 °C, albeit slowly, and exhibit remarkable enantioselectivity with all classes
of aldehydes examined with the exception of aromatic and R-alkoxy aldehydes. Again, while the
selectivity parallels that of the corresponding allylboronate, the reactivities are lower. Also, the
double asymmetric homoallenylboration of 2,3-O-isopropylidene-D-glyceraldehyde using the DMPT
modified boronate reagent gives an excellent 98.5% anti selectivity in the matched case and a
moderately lower value, 82% syn selectivity, in the mismatched case.
A simple, nonasymmetric one-carbon homologation of
some specific classes of these boronates.4 With the
advent of this report, we undertook a systematic study
of all three (halomethyl)lithium reagents (LiCH2X; X )
Cl, Br, and I) to compare their reactivity differences in
the homologation of representative examples of a wide
variety of boronic esters.5 The results of this study
indicated significant reactivity differences among various
boronates. Particularly, R,â-unsaturated boronates, such
as alkenyl- and alkynylboronates, show opposite trends.
The latter reacts much faster with LiCH2I while the
former exhibits little difference in rates among different
LiCH2X (X ) Cl, Br, I) reagents.5 This study led to the
first successful synthesis of “higher” propargylboronates
in 100% isomeric purity.6
Thus, simple one-carbon homologations of R,â-unsatur-
ated boronic esters are not only unique but also syntheti-
cally important, owing to the very high reactivity of the
product â,γ- unsaturated boronates with carbonyl com-
pounds generally known as allylboration.7a Allylboration
has reached a certain maturity and is routinely employed
in modern asymmetric organic synthesis. In the light of
the individual importance of these two methodologies,
viz., homologation and allylboration in organic syntheses,
boronic esters, viz. insertion of a CH2 group between the
carbon and boron atom of the C-B bond, via in situ
generation and capture of (halomethyl)lithiums, LiCH2X,
is an important methodology for a variety of synthetic
transformations.1 The underlying significance of this
process is the fact that the rearrangement of the initially
formed “ate” complex occurs with absolute stereochemical
integrity, thus making it a highly valuable reaction for
general asymmetric organic syntheses using organo-
boranes.1b Subsequent to the pioneering report by Mat-
teson et al., we examined in detail the generation and in
situ capture of LiCH2Cl as an alternative to the prepara-
tion of certain organoboranes not readily available through
hydroboration.1c,2 In spite of the general success of the
LiCH2Cl reagent, occasional problems arising from
â-elimination or oxygen migration spurred the develop-
ment of LiCH2Br as a better reagent.3 Though the higher
reactivity of the LiCH2Br compared to that of LiCH2Cl
was indeed more beneficial, functionalized boronic esters
and certain other classes of boronic esters failed to give
satisfactory results. Recently, Wallace et al. introduced
LiCH2I as an improved alternative for homologation of
(4) Wallace, R. H.; Zong, K. K. Tetrahedron Lett. 1992, 33, 6941.
(5) Soundararajan, R.; Li, G.; Brown, H. C. Tetrahedron Lett. 1994,
35, 8957.
(6) Soundararajan, R.; Li, G.; Brown, H. C. Tetrahedron Lett. 1994,
35, 8961.
(7) (a) For an excellent review on allylboration, see: Yamamoto, Y.;
Asao, N. Chem. Rev. 1993, 93, 2207. (b) Brown, H. C.; Phadke, A. S.;
Bhat, N. G. Tetrahedron Lett. 1993, 34, 7845. (c) Brown, H. C.; Phadke,
A. S. Synlett 1993, 927.
X Abstract published in Advance ACS Abstracts, November 15, 1995.
(1) (a) This is different from the asymmetric homologation of boronic
esters which leads to R-halo boronic esters and has been studied
extensively by Matteson and co-workers. (b) Matteson, D. S. Tetrahe-
dron 1989, 45, 1859 and references therein. (c) Brown, H. C.; Singh,
S. M.; Rangaishenvi, M. V. J . Org. Chem. 1986, 51, 3150.
(2) Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4, 1687.
(3) Michnik, T. J .; Matteson, D. S. Synlett 1991, 631.
0022-3263/96/1961-0100$12.00/0 © 1996 American Chemical Society

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 61, No. 1, 1996 101
and low chemical yields.10 Except for one report by
Takano et al. describing an asymmetric synthesis of these
compounds, albeit in moderate yields, using an expensive
chiral reagent, no other procedure is currently available
for their general synthesis.11 Consequently, it was desir-
able to develop an alternative procedure that would be
general and convenient and yet avoid the problems that
afflict the existing methodologies. Herein, we describe
the racemic and diastereo- and enantioselective syntheses
of alkyl(1,3-butadiene-2-yl)methanols using a novel re-
agent 2,3-butadien-1-ylboronate, readily obtained from
diisopropyl (iodomethyl)boronate and allenylmagnesium
bromide.
Sch em e 1
Resu lts a n d Discu ssion
it appeared possible to us that a unique combination of
these two powerful methodologies would provide valuable
advances in making possible novel applications which
would help extend their usefulness.
The starting diisopropyl 2,3-butadien-1-ylboronate can
be prepared by either of the following two approaches
(Scheme 1): method A, a one-carbon homologation of
allenylboronate using in situ generated LiCH2X or method
B, a reaction of allenylmagnesium bromide with (halo-
methyl)boronates.
This was originally demonstrated in the stereospecific
synthesis of “higher” crotylboronates in excellent stereo-
meric purity.7b Thus, for the first time a tandem ho-
mologation-allylboration approach was used to synthe-
size various optically active tetrahydrofurans and tetra-
hydropyrans in very high enantiomeric purity.7c The
availability of the “higher” propargyl- and “higher” cro-
tylboronates for the first time in 100% isomeric purity
offers significant advantages over other corresponding
main group organometallic reagents based on magne-
sium, silicon, tin, zinc, etc. The fact that all other
organometallic reagents suffer mostly from lack of re-
giomeric integrity, due to rapid 1,3-rearrangement, has
precluded any useful applications based on these re-
agents, especially in asymmetric synthesis. In order to
explore further the unique advantage of the tandem
homologation-allylboration methodology, we extended
the study to allenylboronates.8 We envisaged that,
similar to the behavior of alkenyl- and alkynylboronates,
allenylboronates would also rearrange without isomer-
ization to give rise to homoallenylboronates and that
these homoallenylboronates, being â,γ-unsaturated, would
react with aldehydes in a manner similar to that of
simple allylboronates via 1,3-rearrangement. This se-
quence would then give rise to alkyl(1,3-butadien-2-yl)-
methanols as the final product. Scheme 1 illustrates the
rationale for our approach.
Both method A and method B are equally efficient,
involving the same intermediate ate complex. Diisopro-
pyl allenylboronate itself is not very stable, and hence,
we made the more stable cyclic 1,3-propanediol boronate
and subjected it to homologation by method A. In a direct
comparison using in situ generated LiCH2X, wherein X
) Cl, Br, and I, no significant rate differences are noticed.
The rearrangement from the initial ate complex was
almost complete in less than 5 min after warming to rt.
However, method B proved to be much more convenient
and gave excellent yields under similar reaction condi-
tions. We have routinely employed method B (in g10 g
scale) with high isolated yields. In this way, diisopropyl
2,3-butadien-1-ylboronate is readily prepared in excellent
isomeric purity. Although, Suzuki et al. recently reported
comparable yields of a similar intermediate, the relatively
inert pinacol esters obtained by their procedure greatly
diminishes the possibility of transesterifying the product
with other optically active diols.12,13 In contrast, our
reagent, obtained as diisopropyl boronate by a much
simpler and more direct route, allows unrestricted trans-
esterification with a large number of diols, including
pinacol, tartrate, etc. (vide infra), thus making it much
more versatile for novel variations and applications.14
In contrast to the instability of the diisopropyl allen-
ylboronate, diisopropyl 2,3-butadien-1-ylboronate is a
thermally stable compound and can be stored for ex-
tended periods of time, with complete exclusion of air and
moisture, without noticeable deterioration in quality.
Syn th esis of Ra cem ic Alk yl(1,3-bu ta d ien -2-yl)-
m eth a n ols. This boronate reagent readily reacts with
a series of aldehydes. The product alkyl(1,3-butadien-
2-yl)methanols are obtained exclusively, thus demon-
These alkyl(1,3-butadien-2-yl)methanols are valuable
starting materials for the syntheses of a variety of
natural products.9 For example, they have been success-
fully employed for the enantio- and stereocontrolled
synthesis of branched chain sugars, such as L-arcanose
and L-olivomycose.9a These chiral 2-substituted 1,3-
dienes are potentially valuable intermediates in provid-
ing a new route to the enantioselective synthesis of
polyfunctionalized cyclohexanes via the Diels-Alder
reaction.9b However, current methodologies for their
synthesis are far from ideal; they suffer from poor
regiospecificity, providing a complex mixture of products
(10) (a) Nativi, C.; Taddei, M.; Mann, A. Tetrahedron 1989, 45, 1131.
(b) J enkins, P. R.; Brown, P. A. J . Chem. Soc., Perkin Trans. 1 1986,
1129. (c) J enkins, P. R.; Brown, P. A. Tetrahedron Lett. 1982, 23, 3733.
(d) Wada, E.; Kanemasa, S.; Fujiwara, I.; Tsuge, O. Bull. Chem. Soc.
J pn. 1985, 58, 1942. (e) Nunomoto, S.; Yamashita, Y. J . Org. Chem.
1979, 44, 4788. (f) Kondo, K.; Dobashi, S.; Matsumoto, M. Chem. Lett.
1976, 1077.
(11) Hatakeyama, S.; Sugawara, K.; Kawanmura, M.; Takano, S.
Tetrahedron Lett. 1991, 32, 4509.
(12) Gridnev, I.; Kanai, G.; Miyaura, N.; Suzuki, A. J . Organomet.
Chem. 1994, 481, C4.
(13) All our attempts to transesterify the pinacol 2,3-butadien-1-
ylboronate esters with tartrates failed.
(14) Diisopropyl 2,3-butadien-1-ylboronate can readily be transes-
terified with pinacol in quantitative yield. The spectral characteristics
of this pinacol derivative was identical was reported values.12
(8) Soundararajan, R.; Li, G.; Brown, H. C. Tetrahedron Lett. 1995,
36, 2441.
(9) (a) Hatakeyama, S.; Sugawara, K.; Takano, S. Tetrahedron Lett.
1991, 32, 4513. (b) Hatakeyama, S.; Sugawara, K.; Takano, S. J . Chem.
Soc., Chem. Commun. 1992, 953. (c) Bloch, R.; C-Gradoz, N. Tetrahe-
dron Lett. 1992, 33, 6147. (d) Tebbe, M. J .; Wender, P. A. Synthesis
1991, 1059. (e) Brown, P. A.; Bonnert, R. V.; J enkins, P. R.; Lawrence,
N. J .; Selim, M. R. J . Chem. Soc., Perkin Trans. 1 1991, 1893. (f) Wada,
E.; Fujiwara, I.; Kanemasa, S.; Tsugi, O. Bull. Chem. Soc. J pn. 1987,
60, 325. (g) Krief, A.; Halazy, S. Tetrahedron Lett. 1980, 21, 1997.

102 J . Org. Chem., Vol. 61, No. 1, 1996
Soundararajan et al.
Ta ble 1. Hom oa llen ylbor a tion of Rep r esen ta tive
Ald eh yd es, RCHO, w ith Diisop r op yl
2,3-Bu ta d ien -1-ylbor on a tea
Sch em e 3
no.
R
solvent
time
yield (%)b
1
2
3
4
5
6
7
8
9
Et
Et
PhCH3
neat
3 h
1 h
8 h
3 d
30 h
4 h
1 h
0.5 h
5 h
3 d
84
82
80
60
91
91
90
85
95
59
93c,d
i-Pr
t-Bu
Chx
Chx
Chx
Ph
PhCH3
PhCH3
CH2Cl2
PhCH3
neat
PhCH3
CH2Cl2
CH2Cl2
CH2Cl2
study by Takano et al. using 2,3-butadien-1-yltrimeth-
ylsilane. The silicon reagent generally gives high syn
selectivity in lower yields, in direct contrast to the very
high anti selectivity and higher yields exhibited by our
reagent. The difference in their behavior is due to the
presence of chelating Lewis acids such as TiCl4 and SnCl4
used under Takano’s conditions, and their behaviors are
in good agreement with the expected behavior of both
allylboranes and allylsilanes.15
Thus, for the first time our reagent offers a unique and
complementary procedure for the synthesis of anti-
substituted derivatives with major advantages over the
existing procedures. It is pertinent to note that the 92%
ds obtained could probably be improved with another
choice of an ester group with modified stereoelectronic
factors.
(E)-PhCHdCH
PhCH2OCH2
10
11
12 h
O
O
12
PhCH3
4 h
90e
O
O
a
1.2 equiv of the reagent was used; unless otherwise specified
the reactions were carried out at rt. Isolated yields of pure
b
products; all compounds gave satisfactory spectral and analytical
data. c Anti:syn ) 87:13 at rt; anti:syn ) 92:8 at 0 °C. The anti:
d
syn ratios were determined by GC analyses and by 1H NMR. e Anti:
syn ) 89:11.
En a n tioselective Syn th esis. Encouraged by these
results we examined the application of this methodology
to the enantioselective synthesis. Prompted by the
successful use of tartrates as chiral directors in allylbo-
ration and in allenylboration studied extensively by
Roush and Yamamoto, respectively, we selected diiso-
propyl tartrate (DIPT) and bis(2,4-dimethyl-3-pentyl)
tartrate (DMPT) as chiral modifiers for our study.16 In
light of our earlier results that DMPT proved to be better
than DIPT for the higher crotylborations, we initially
examined both reagents under otherwise identical condi-
tions (Scheme 3).7b The respective tartrate boronates can
be conveniently prepared from the diisopropyl 2,3-buta-
dien-1-ylboronate and the two tartrates by a simple
transesterification and can be used without isolation in
the next step. These readily accessible and synthetically
convenient reagents exhibit good to excellent enantiose-
lectivity. The results of this reaction with a series of
aldehydes are presented in Table 2.
Once again, we observed that generally DMPT is
slightly better than DIPT in terms of selectivity while
the chemical yields are identical. It is important to note
that the selectivity in terms of absolute configuration of
the product alcohols is similar to that observed for
allylboration with any given tartrate reagent. Toluene
proved to be the solvent of choice, and a slight excess of
the chiral tartrate (1.5 equiv) provides better enantiose-
lectivity. But, a further increase in the amount of the
chiral reagent (g2.0 equiv) serves only to accelerate the
reaction moderately with negligible effect on the enan-
tioselectivity. Some substrates, such as benzaldehyde
and R-alkoxy aldehydes, give lower ee. Surprisingly,
DMPT is worse than DIPT for benzaldehyde. Though
the reason for this decreased selectivity is unclear,
similar results were observed by Yamamoto in the
allenylboration of benzaldehyde. A possible explanation
Sch em e 2
strating that the reaction proceeds via a facile 1,3-
rearrangement. The reaction can be conveniently moni-
tored by observing at regular intervals the 11B NMR
signals (starting boronate: δ 29 ppm; product borate δ
18 ppm).
The results of this reaction with different aldehydes
under various conditions are summarized in Table 1. The
reactivity of this homoallenylboronate is lower than that
of the corresponding allylboronate. This is not unex-
pected considering the reduced HOMO electron density
of the internal π bond with a resultant diminished ability
to undergo 1,3-rearrangement. As a result, the reaction
times are considerably longer in a given solvent, espe-
cially so at lower temperatures. Not surprisingly, the
reaction is much faster under neat conditions, presum-
ably due both to the higher concentrations and the
enhanced coordination of the boron with the carbonyl
oxygen in the transition state, facilitating the rearrange-
ment. The reaction is faster in toluene than in CH2Cl2
at all temperatures. Also, sterically hindered aldehydes,
such as isobutyraldehyde and pivalaldehyde, react much
slower. These results strongly suggest a six-membered
cyclic transition state model, such as is generally accepted
for allylboration.
Dia ster eoselective Syn th esis. In order to elucidate
the diasteroselectivity of the reagent, we examined the
reaction with an R-chiral aldehyde, viz., 2,3-O-isopropyl-
idene-D-glyceraldehyde (Scheme 2). The initial lower
selectivity obtained in CH2Cl2 (87:13; anti:syn) improved
to give a very high anti selectivity (92:8; anti:syn) in
excellent chemical yields (Table 1) when the temperature
was lowered to 0 °C. The high anti selectivity obtained
merits some discussion especially in the light of a related
(15) Mash, E. A. In Studies in Natural Product Chemistry; Atta-
ur-Rahman, Ed.; Elsevier Science Publishing: New York, 1988; Vol.
1, pp 557-653.
(16) (a) For reasons of NaBH4 additions and its effects, see: Roush,
W. R.; Hoong, L. K.; Palmer, M. A. J .; Park, J . C. J . Org. Chem. 1990,
55, 4109. (b) Yamamoto, H. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, p 81.
(c) Ikeda, N.; Arai, I.; Yamamoto, H. J . Am. Chem. Soc. 1986, 108,
483.

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 61, No. 1, 1996 103
Ta ble 2. Asym m etr ic Hom oa llen ylbor a tion of Rep r esen ta tive Ald eh yd es, RCHO, Usin g
2-(2,3-Bu ta d ien -1-yl)-1,3,2-d ioxa bor ola n e-4,5-d ica r boxyla tesa
no.
R
tartrate
yieldb (%)
eec (%)
abs confignd
[R]D (deg) (c, CHCl3)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Me
Me
Et
L-DMPT
D-DMPT
L-DMPT
D-DMPT
L-DMPT
D-DMPT
L-DIPT
L-DMPT
D-DMPT
D-DIPT
L-DMPT
D-DMPT
L-DIPT
D-DIPT
D-DMPT
L-DMPT
75
82
-
61.0
59.8
81.3
81.9
87.9
88.4
80.7
88.9
89.6
84.9
38.3
36.5
43.3
48.7
48.2
50.1
R
S
R
S
R
S
R
R
S
S
S
R
S
R
R
S
+12.10 (4.00)
-12.80 (3.50)
+10.90 (3.00)
-11.20 (5.75)
-15.76 (6.55)
+15.76 (6.55)
-13.60 (3.00)
-6.00 (3.25)
+6.35 (2.30)
Et
74
79
82
80
94
92
94
89
86
95
90
29e
36e
i-Pr
i-Pr
i-Pr
Chx
Chx
Chx
Ph
Ph
Ph
-37.07(2.05)
+35.81(2.15)
-50.10 (5.70)
Ph
BnOCH2
BnOCH2
+6.40 (0.50)
a
See Experimental Section for a representative procedure. b Isolated yields of pure products. c Determined by capillary GC analyses of
d
the corresponding TFA derivatives on Chiraldex-GTA. The absolute configurations are assigned on the basis of literature data for entry
8, and the others are assigned by analogy to this data. e Quenched with NaBH4 at -78 °C and estimated by GC.
Sch em e 4
tartrate boronate esters of this reagent are readily
prepared from the starting diisopropyl 2,3-butadien-1-
ylboronate and usually exhibit excellent enantioselectiv-
ity with the exception of aromatic aldehydes. The reason
for the poorer selectivity in the case of aromatic and
alkoxy aldehydes is not readily apparent. However, there
is a strong possibility that unfavorable electronic interac-
tions, especially in the transition state, could be respon-
sible for this observation. The double asymmetric ho-
moallenylboration using 2,3-O-isopropylidene-D-glyc-
eraldehyde gives 98.5% anti selectivity and 82% syn
selectivity with matched and mismatched tartrate bor-
onate, respectively.
Exp er im en ta l Section
could be an unfavorable interaction between the rich π
electron clouds of the proximate allenyl and phenyl
groups in the six-membered cyclic transition state.
In comparison to the only other report in the literature
for the enantioselective synthesis of alkyl(1,3-butadien-
2-yl)methanols by Takano et al., our method is more
general and avoids the use of expensive chiral directors
while the optical induction obtained is either comparable
or even better in most cases.
Dou ble Asym m etr ic Syn th esis. Homoallenylbora-
tion of a chiral aldehyde, 2,3-O-isopropylidene-D-glycer-
aldehyde, with DMPT-modified 2,3-butadien-1-ylboronate
afforded in high selectivity the anti product under similar
reaction conditions in the matched case (Scheme 4). We
observed that the initial poorer selectivity exhibited by
D-DMPT (53:47; anti:syn) could be improved provided the
reactions were quenched with NaBH4 in EtOH at -78
°C prior to workup.16a Thus, we achieved 82% syn
selectivity with D-DMPT as compared to g98.5% anti
selectivity with L-DMPT.
Gen er a l Rem a r k s. All air and moisture sensitive reac-
tions were carried out under nitrogen using oven-dried glass-
ware. THF was freshly distilled from sodium benzophenone
ketyl. Anhydrous Et2O and toluene were kept over 4 Å
molecular sieves for several days prior to use. Allenylmag-
nesium bromide was freshly prepared and titrated according
to published procedure.17,18 L- and D-bis(2,4-dimethyl-3-pentyl)
tartrate (DMPT) were prepared from the corresponding tar-
taric acids and 2,4-dimethyl-3-pentanol using CH3SO3H as the
catalyst.19 2,3-O-Isopropylidene-D-glyceraldehyde was freshly
prepared according to a reported procedure.20 For homoallen-
ylboration reactions with diisopropyl 2,3-butadien-1-ylboronate
and the DIPT ester of 2,3-butadien-1-ylboronic acid, the
workup included direct hydrolysis of the reaction mixture with
H2O and extraction with CH2Cl2, followed by column chroma-
tography on silica gel using CH2Cl2 as the eluent unless
otherwise indicated. For those reactions with the DMPT ester
of 2,3-butadien-1-ylboronic acid, DMPT was removed either
by hydrolysis with excess MeONa/MeOH prior to the usual
workup or by Kugelrohr distillation before column chromato-
graphic isolation.
11B chemical shifts (δ) are given in ppm relative to the
external standard BF3‚Et2O. Chiral GC analyses were carried
out on Chiraldex-GTA.
P r ep a r a tion of Diisop r op yl (Iod om eth yl)bor on a te. A
solution of n-BuLi in hexane (40.0 mL, 100 mmol) was slowly
transferred to a mixture of (OiPr)3B (23.1 mL, 100 mmol) and
CH2I2 (8.1 mL, 100 mmol) in THF (50 mL) at -78 °C while
the solution was stirred. After addition, the mixture was
Con clu sion s
This is the first detailed report of a novel homoallen-
ylboration including diastereo- and enantioselective stud-
ies. We have developed a simple and efficient route for
the synthesis of diisopropyl 2,3-butadien-1-ylboronate
(homoallenylboronate) in 100% isomeric purity. This
homoallenylboronate reagent reacts readily with alde-
hydes via 1,3-rearrangement to give exclusively alkyl-
(1,3-butadien-2-yl)methanols in excellent yields. With an
R-chiral aldehyde, this reagent exhibits a very high anti
diastereoselectivity. The DIPT- and DMPT-modified
(17) Hope, H.; Bohm, I.; Kleinschroth, J . Org. Synth. 1981, 60, 485.
(18) Liu, H.-S.; Paquette, L. A. Synth. Commun. 1994, 24, 2503.
(19) Brown, H. C.; J ayamani, M.; Racherla, U. S. Unpublished
results.
(20) Schmid, C. R.; Bryant, J . D.; Dowlatzedah, M.; Phillips, J . L.;
Prather, D. E.; Schantz, R. D.; Sear, N. L.; Viance, C. S. J . Org. Chem.
1991, 56, 4056.

104 J . Org. Chem., Vol. 61, No. 1, 1996
Soundararajan et al.
stirred at -78 °C for an additional 0.5 h, followed by quenching
the reaction with anhydrous HCl in Et2O (105 mL, 105 mmol).
The cold bath was removed, and the mixture was allowed to
warm to rt for 1 h. The solid was filtered off under N2 and
washed with Et2O (3 × 20 mL). The combined ethereal
solution was concentrated, and the residue was distilled under
reduced pressure in the presence of copper wires (cut into 0.2
cm long) to afford an almost colorless liquid (18.8 g, 92-94 °C
at 30 mmHg) in 70% yield. 11B NMR (CDCl3): δ 27.6. 1H
NMR (CDCl3): δ 4.39 (septet, 6 Hz, 2H), 2.12 (s, 2H), 1.19 (d,
6 Hz, 12H). 13C NMR (CDCl3): δ 66.06, 24.23. IR (neat, cm-1):
2972, 2919, 2872, 1401, 1336, 1284, 1171, 1117, 1021, 907. MS
m/ z: (EI) 270 (M+), (CI) 271 (MH+), 229 (MH+ - C3H6, base).
HRMS found 271.0229, calcd for C7H16BO2I 271.0366.
3-Meth ylen e-4-p en ten -2-ol.21 Colorless liquid. 1H NMR
(CDCl3): δ 6.36 (dd, 18 Hz, 11 Hz, 1H), 5.33 (d, 18 Hz, 1H),
5.28 (m, 1H), 5.13 (d, 11 Hz, 1H), 5.12 (s, 1H), 4.65 (m, 1H),
1.57 (d, 4 Hz, 1H), 1.37 (d, 6 Hz, 3H), 1.37 (d, 6 Hz, 3H). 13C
NMR (CDCl3): δ 150.31, 136.28, 114.24, 113.25, 67.16, 22.79.
4-Met h ylen e-5-h exen -3-ol. Colorless liquid. 1H NMR
(CDCl3): δ 6.35 (dd, 18 Hz, 11 Hz, 1H), 5.34 (d, 18 Hz, 1H),
5.23 (d, 1 Hz, 1H), 5.16 (s, 1H), 5.11 (d, 11 Hz, 1H), 4.36 (m,
1H), 1.89-1.55 (m, 3H), 0.85 (t, 7 Hz, 3H). 13C NMR (CDCl3):
δ 148.85, 136.21, 114.18, 114.03, 72.81, 29.02, 9.92. IR (neat,
cm-1): 3366, 3085, 1591, 981, 904. MS m/ z: (EI) 112 (M+),
95 (M+ - OH), (CI) 95 (base, MH+ - H2O). HRMS found
112.0892, calcd C7H12O 112.0888.
2-Meth yl-4-m eth ylen e-5-h exen -3-ol.10a Colorless liquid.
1H NMR (CDCl3): δ 6.34 (d, 18 Hz, 11 Hz, 1H), 5.35 (d, 18 Hz,
1H), 5.20 (s, 1H), 5.17 (s, 1H), 5.10 (d, 11 Hz, 1H), 4.13 (m,
1H), 1.90 (m, 1H), 1.51 (d, 4 Hz, 1H), 0.93 (d, 7 Hz, 6H). 13C
NMR (CDCl3): δ 148.31, 136.23, 114.59, 114.43, 71.21, 31.95,
19.63, 19.93. IR (neat, cm-1): 3413, 3079, 1591, 1000, 904.
2,2-Dim eth yl-4-m eth ylen e-5-h exen -3-ol.10d Colorless liq-
uid. 1H NMR (CDCl3): δ 6.37 (dd, 18 Hz, 11 Hz, 1H), 5.36 (d,
18 Hz, 1H), 5.32 (s, 1H), 5.15 (s, 1H), 5.04 (d, 11 Hz, 1H), 4.15
(d, 3 Hz, 1H), 1.669 (d, 3 Hz, 1H), 0.93 (s, 9H); 13C NMR
(CDCl3): δ 148.13, 137.86, 115.50, 113.71, 78.59, 35.39, 26.25.
(1E)-4-Met h ylen e-1-p h en yl-1,5-h exa d ien -3-ol.10d Vis-
cous oil. 1H NMR (CDCl3): δ 7.80-7.40 (m, 5H), 6.64 (d, 16
Hz, 1H), 6.36 (dd, 18 Hz, 11 Hz, 1H), 6.27 (dd, 16 Hz, 6 Hz,
1H), 5.42 (d, 18 Hz, 1H), 5.35 (s, 1H), 5.23 (s, 1H), 5.13 (d, 11
Hz, 1H), 5.04 (d, 6 Hz, 1H), 2.18 (s, 1H). 13C NMR (CDCl3):
δ 147.26, 136.52, 135.78, 131.11, 128.48, 127.66, 126.49,
115.17, 115.09, 72.10.
1-(Ben zyloxy)-3-m eth ylen e-4-p en ten -2-ol. Colorless oil
(eluent for chromatography was CH2Cl2:EtOAc ) 20:1). 1H
NMR (CDCl3): δ 7.32 (m, 5H), 6.31 (dd, 18 Hz, 11 Hz, 1H),
5.37 (s, 1H), 5.24 (d, 18 Hz, 1H), 5.20 (s, 1H), 5.05 (d, 11 Hz,
1H), 4.67 (m, 1H), 4.55 (s, 2H), 3.64 (dd, 10 Hz, 3 Hz, 1H),
3.37 (dd, 10 Hz, 9 Hz, 1H), 2.87 (d, 3 Hz, 1H). 13C NMR
(CDCl3): δ 144.65, 137.72, 136.27, 128.33, 127.68, 127.64,
115.84, 113.77, 74.21, 73.17, 69.72. IR (neat, cm-1): 3439,
3079, 3025, 1591, 1104, 907, 734, 697. MS m/ z: (EI) 204 (M+),
91 (base), (CI) 205 (MH+), 169 (base). HRMS found 205.1219,
calcd for C13H16O2 205.1229.
(2R,3S)-1,2-O-Isop r op ylid en e-4-m eth ylen e-5-p en ten e-
1,2,3-tr iol. Colorless liquid (eluent for chromatography was
CH2Cl2:EtOAc ) 5:1). 1H NMR (CDCl3): δ 6.35 (dd, 18 Hz,
11 Hz, 1H), 5.43 (d, 1 Hz, 1H), 5.32 (18 Hz, 1H), 5.23 (d, 1 Hz,
1H), 4.72 (d, 3 Hz, 1H), 4.31 (dt, 3 Hz, 7 Hz, 1H), 3.91 (dd, 7
Hz, 8 Hz, 1H), 3.81 (dd, 7 Hz, 8 Hz, 1H), 2.47 (br, 1H), 1.48 (s,
3H), 1.37 (s, 3H); 13C NMR (CDCl3): δ 143.75, 136.23, 15.95,
114.08, 109.44, 76.72, 68.94, 63.80, 26.34, 25.00. IR (neat,
cm-1): 3459, 3085, 1588, 1061, 907; MS (EI) m/ z: 169 (M -
Me), 101 (base); (CI) 185 (MH+), 167 (MH+ - H2O). HRMS
found 185.1182, calcd for C10H16O3 185.1178.
P r ep a r a tion of Diisop r op yl 2,3-Bu ta d ien -1-ylbor on a te.
Freshly prepared allenylmagnesium bromide (50 mmol, 1.54
M in Et2O) was slowly added to a precooled solution of (Oi-
Pr)2BCH2I (13.60 g, 50 mmol) in THF (30 mL) at -78 °C while
the solution was stirred vigorously. The resulting white
suspension was stirred at -78 °C for another 0.5 h. The cold
bath was then removed, and the mixture was stirred at rt for
20 h. The solution was separated from the solid under N2 by
means of a cannula and was concentrated. The residue was
distilled to give a colorless liquid (7.52 g, 58-60 °C /15 mmHg)
in 72% yield. 11B NMR (CDCl3): δ 29.3. 1H NMR (CDCl3): δ
5.18 (m, 1H), 4.60 (dt, 7 Hz, 3 Hz, 2H), 4.40 (septet, 6 Hz, 2H),
1.58 (m, 2H), 1.16 (d, 6 Hz, 12H). 13C NMR (CDCl3): δ 73.86,
86.60, 65.42, 24.38. IR (neat, cm-1): 1949, 1410, 1340, 1120,
840.
P r ep a r a tion of th e P in a col Ester of 2,3-Bu ta d ien -1-
ylbor on a te. Pinacol (0.328 g, 2.78 mmol) and diisopropyl 2,3-
butadien-1-ylboronate (0.506 g, 2.78 mmol) were mixed in dry
pentane (5 mL), and the mixture was stirred at rt for 1 h.
Removal of pentane and isopropanol under vacuum gave a
quantitative yield of the pinacol ester of 2,3-butadien-1-
ylboronate. 11B NMR (CDCl3): δ 32.98. 1H NMR (CDCl3):12
δ
5.15 (m, 1H), 4.63 (dt, 7 Hz, 3 Hz, 2H), 1.61 (m, 2H), 1.26 (s,
12H). 13C NMR (CDCl3): δ 85.37, 83.43, 74.32, 24.80.
Rep r esen ta tive P r oced u r e for Rea ction s of th e DMP T
Ester of 2,3-Bu ta d ien -1-ylbor on a te w ith Ald eh yd es. To
a mixture of L-DMPT (0.843 g, 2.43 mmol), powdered molecular
sieves (0.5 g), and PhMe (5 mL) was added diisopropyl 2,3-
butadien-1-ylboronate (0.25 mL, 1.21 mmol). The reaction
mixture was stirred at rt for 1 h, and the apparatus was
connected to a vacuum (15 mmHg) for approximately 3 h while
the mixture was stirred. 11B NMR indicated diisopropyl 2,3-
butadien-1-ylboronate (δ ∼29 ppm) was completely converted
to the DMPT ester of 2,3-butadien-1-ylboronic acid (δ ∼34
ppm). Nitrogen was then allowed into the flask, and PhMe (2
mL) was added. The mixture was cooled to -78 °C, and
cyclohexanecarboxaldehyde (0.10 mL, 0.82 mmol) was added
slowly while the mixture was stirred. After it was stirred for
72 h at -78 °C, the reaction was quenched with excess 25%
MeONa in MeOH to hydrolyze DMPT, and the mixture was
extracted with Et2O (3 × 10 mL). The combined ethereal
solution was concentrated, and the residue was chromato-
graphed on silica gel with CH2Cl2 as the eluent to provide (R)-
cyclohexyl(1,3-butadien-2-yl)methanol as a colorless oil (0.128
(2R,3R)-1,2-O-Isop r op ylid en e-4-m eth ylen e-5-p en ten e-
1,2,3-tr iol. 1H NMR (CDCl3): δ 6.37 (dd, 18 Hz, 11 Hz, 1H),
5.44 (d, 18 Hz, 1H), 5.29-5.28 (m, 2H), 5.15 (d, 11 Hz, 1H),
4.28 (s, 1H), 4.24 (q, 6 Hz, 1H), 3.97 (dd, 6 Hz, 8 Hz, 1H), 3.76
(dd, 6 Hz, 8 Hz, 1H), 2.58 (s, 1H), 1.48 (s, 3H), 1.37 (s, 3H).
13C NMR (CDCl3): δ 145.00, 135.94, 116.87, 115.18, 109.91,
78.15, 72.59, 66.22, 26.77, 25.31.
g) in 94% yield. [R]25 ) -6.0° (c, 3.25, CHCl3) (lit.11 [R]29
)
D
D
5.8°, CHCl3, 88% ee). This alcohol was analyzed by capillary
GC as its TFA derivative on a Chiraldex-GTA column at 75
°C to reveal 89% ee in (R) isomer. Retention times for the
Ack n ow led gm en t. We gratefully acknowledge the
financial support from the Borane Research Fund which
made this study possible.
1
(R)- and (S)-isomer are 45.18 and 54.26 min, respectively. H
NMR (CDCl3): δ 6.33 (dd, 18 Hz, 11 Hz, 1H), 5.37 (d, 18 Hz,
1H), 5.20 (s, 1H), 5.09 (d, 11 Hz, 1H), 4.12 (m, 1H), 1.90-1.50
(m, 7H), 1.30-0.95 (m, 5H). 13C NMR (CDCl3): δ 147.93,
136.09, 114.63, 114.32, 76.65, 41.70, 29.81, 27.64, 26.34, 26.23,
25.98. IR (neat, cm-1): 3386, 3085, 1591, 1000, 904. MS
m/ z: (EI) 166 (M+), 55 (base), (CI) 149 (MH+ - H2O, base).
HRMS found 166.1355, calcd for C11H18O 166.1358.
2-Meth ylen e-1-p h en yl-3-bu ten -1-ol.10d Colorless oil. 1H
NMR (CDCl3): δ 6.32 (dd, 18 Hz, 11 Hz, 1H), 5.47 (d, 4 Hz,
1H), 5.41 (d, 1 Hz, 1H), 5.33 (s, 1H), 5.23 (d, 18 Hz, 1H), 5.04
(d, 11 Hz, 1H), 2.01 (d, 4 Hz, 1H). 13C NMR (CDCl3): δ 147.44,
141.87, 135.74, 128.37, 127.69, 126.84, 115.62, 115.33, 73.77.
IR (neat, cm-1): 3359, 3085, 3025, 1591, 1451, 1014, 764, 697.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR of the optically active alkyl(1,3-butadien-2-yl)methanols
(17 pages). This material is contained in libraries on micro-
fiche, immediately following this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any masthead page for ordering information.
J O9513976
(21) Franck-Neumann, M-.; Martina, D. M.; Heitz, M.-P. J . Orga-
nomet. Chem. 1986, 301, 61.