(E)-2-boryl-1,3-butadiene derivatives of the 10-TMS-9-BBDs: Highly selective reagents for the asymmetric synthesis of anti-1,2-disubstituted 3,4-pentadien-1-ols

Article abstract of DOI:10.1021/ja9047202

(Chemical Equation Presented) The efficient stepwise construction of optically pure trans-4-substituted 2-boryl-1,3-butadienes 6 is described. Hydroboration of 1-alkynes with either enantiomeric form of 3 leads to the pure trans-1-alkenylboranes 4 which u

Full text of DOI:10.1021/ja9047202

Published on Web 07/06/2009
(E)-2-Boryl-1,3-butadiene Derivatives of the 10-TMS-9-BBDs: Highly Selective
Reagents for the Asymmetric Synthesis of anti-1,2-Disubstituted
3,4-Pentadien-1-ols
Javier R. Gonza´lez, Ana Z. Gonza´lez, and John A. Soderquist*
UniVersity of Puerto Rico, Department of Chemistry, Rio Piedras, PR 00931-3346
Received June 9, 2009; E-mail: jasoderquist@yahoo.com
Table 1. 2-Butadienylboration of Aldehydes with the
Because of the immense synthetic importance of asymmetric
allylation and related conversions, these processes continue to
evolve within both the stoichiometric and catalytic arenas. One
developing area can be found in the use of unsaturated organobo-
ranes to provide γ-substituted allenyl or allylboranes stereoselec-
tively through carbenoid insertion processes.1 These reagents expand
the scope of “crotylation” by introducing a wide variety of groups
into the ꢀ-stereogenic position of the resulting homopropargylic
or homoallylic alcohols. Robust spectator ligation is essential to
effectively orchestrate each step of the process with complete
stereocontrol. We chose to push the limits of the remarkable 10-
TMS-9-borabicyclo [3.3.2] decanes (10-TMS-9-BBDs)1a,b,2 to
selectively direct sequential organoborane conversions en route to
nonracemic trans-2-boryl-1,3-dienes (6). We envisaged 6 as a new
type of asymmetric allylborating agent to provide ꢀ-substituted
nonracemic chiral homoallenic carbinols 8. Our reaction sequence
is shown in Scheme 1.
10-TMS-9-BBDs
abs.
config.
d
6
R1
e
R2
8
yielda
drb
eec
aR
aS
bR
cR
bR
bS
bR
bR
dS
eS
Ph
Ph
Ph
Pr
a
a
b
c
d
e
e
f
75
75
74
65
73
72
66
56
78
75
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
99
99
98
99
98
99
99
99
99
99
1R,2R
1S,2S
1R,2R
1S,2S
1S,2R
1S,2S
1R,2R
1R,2R
1S,2S
1S,2S
Me
Me
e
n-C5H11
Ph
n-C5H11
n-C5H11
n-C5H11
n-C5H11
(CH2)4Cl
c-Pr
Pr
p-MeOC6H4
p-MeOC6H4
o-ClC6H4
Ph
g
h
Ph
a Isolated yields of analytically pure material. b No signals
attributable to the syn alcohols were observed by NMR for 8 where 1%
would be observable. c Product ee was determined by 31P NMR of the
Alexakis esters of 8. d The absolute configuration of 8d was determined
by its conversion to 12 whose optical rotation is known.10 The 1,2
notation refers to the stereogenic centers in 8 where the alcohol carbon
is C-1. e (1R,2R)-8a (cf. [R] ) +96.5 (c 1.2, CH2Cl2, g99% ee) vs
(1S,2S)-(8a) [R] ) -96.8 (c 1.2, CH2Cl2, g99% ee)).
Scheme 1
employed in Diels-Alder cycloadditions,4 and related reagents do add
to aldehydes with allylic transposition.5 Isolable as pure, stable
compounds, 6 appeared to us to have the ideal properties for developing
highly selective new reagents for this unusual type of asymmetric
allylboration. The versatility inherent in the above protocol for
variations in both R1 and R2 makes this route to nonracemic allene-
containing alcohols 8 very attractive.
Recently,2g,h we reported the hydroboration of representative alkene
types with 3 generating the reagent from the air-stable crystalline 1 with
LiAlH3(OEt) followed by TMSCl.6 With the alkyne present, its in situ
hydroboration with 3 gives 4 which can be isolated in g96% yield by
simple filtration and concentration. Unlike 9-BBN-H, 3 undergoes only
the monohydroboration of 1-alkynes to provide 4 cleanly.7
The 4f6 conversion benefits from the fact that 5 is formed as a
single isomer (11B NMR δ -15) having the geometry shown
in Scheme 1 based upon confirming NOESY data and calculations
supporting the cis relationship of the alkenyl and TMS groups (see
Supporting Information). This permits both access to the ethoxy group
by the BF3 and its anti conformation relative to the alkenyl group which
undergoes BfC migration. In contrast to 9-BBN systems, the BBD
ring resists migrations of this type resulting in the exclusive formation
of 6.8 After the reaction is complete, the addition of (i-Pr)2NEt forms
BF3 adducts which precipitate, facilitating the isolation of 6. The trans
stereochemistry of 4 is preserved in 6 (3JH-H ) 16-17 Hz).
The conversion of 1f6, while a complex multistep sequence, is
operationally quite simple producing 6 as stable reagents for a new
type of asymmetric allylboration process. The addition of representative
aldehydes to 6 at -78 °C results in a smooth allylboration in e12 h
as evidenced by the disappearance of the 11B NMR signal for 6 at δ
829 with the concomitant formation of 7 at δ 55. After an oxidative
First reported by Negishi, 2-boryl-1,3-butadienes are known to
undergo oxidation and protonolysis to give the expected dienes and
R,ꢀ-unsaturated ketones, repectively.3 These boranes can also be
9
9924 J. AM. CHEM. SOC. 2009, 131, 9924–9925
10.1021/ja9047202 CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
As illustrated in Figure 1, the most stable B-chiral pretransition state
aldehyde-6 (i.e., 14) complex positions the aldehyde cis to the TMS
group in an anti aldehyde-6 adduct which is down with respect to
the BBD ring. A steric-based preference for a chairlike transition state
with these geometrical features was recently supported by calculations
at the B3LYP/6-31G* level for allylboration with the BBD reagents.13
In summary, this work reports the efficient stepwise construction
of optically pure 2-boryl-1,3-butadienes 6. As a new type of asymmetric
allylborating agent, 6 provides an extremely selective protocol for the
preparation of anti-1,2-disubstituted 3,4-pentadien-1-ols 8 as essentially
single diastereomers in enantiomerically pure form. The conversion
of 8 to substituted ꢀ-hydroxy acids 12 through ozonolysis and to
nonracemic δ-lactones 13 through Ru-catalyzed cyclocarbonylation
was demonstrated.
Figure 1. Pretransition state complex 14 with Spartan 06-generated space-
filling model.
workup (30% H2O2, 3 M NaOH), silica gel chromatography provides
the homoallenic carbinols 8 in 54-74% yield as essentially single
compounds (Table 1).
Acknowledgment. This work is dedicated to Professor Clayton
H. Heathcock. The support of the NSF (CHE-0848192) is gratefully
acknowledged. We thank Dr. Eda Canales and Mr. Jose´ Betancourt
for their help with this study.
Supporting Information Available: Experimental procedures,
analytical data, and selected spectra for 1-13, 15, and derivatives. This
material is available free of charge via the Internet at http://pubs.acs.org.
Employing the Grignard reagent derived from cis-1-bromopro-
pene, we prepared the cis-vinylboranes 9 (10S, 10R, and (()-9,
96%, Z/E ) 96:4). These were converted to the cis-dienes 10 (3JH-H
) 10 Hz) which add smoothly to PhCHO to give the syn-alcohols
11 (71%, dr ) 96:4, 99% ee). This provided us with comparative
data for the diastereomeric composition of 8a whose NMR signals
were well resolved from those of 11. From (()-3, racemic alcohols
(()-8 were prepared and converted to the corresponding Alexakis
esters for analysis by 31P NMR. Under conditions where e1% of
the isomeric esters was observable, the enantiomeric purity of 8
was determined to be 98-99% ee. Under these conditions and by
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1
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While the absolute stereochemistry of 8 was predictable based upon
a wide range of related asymmetric conversions with the 10-TMS-9-
BBD systems, we chose to convert 8d to the known (2R,3S)-ꢀ-hydroxy
acid 12 (80%) through ozonolysis to confirm our assignments.10 As
is apparent from this result, the 6f8f12 conversion provides a
potentially very versatile route to anti-R-substituted ꢀ-hydroxy acids
of high optical purities.
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signals (δ 80-82) compared to their vinylic precursors 4 (δ 72-74)
suggesting that boron’s -K effect is essentially absent in 6 (see: Soderquist,
J. A.; Santiago, B. Tetrahedron Lett. 1990, 31, 5113. This contrasts with
1-(10′-TMS-9′-BBD)-3-methyl-1,3-butadiene 15 (δ 72) where the -K effect
is uninhibited (see Supporting Information).
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cyclocarbonylation.11 Through this conversion, it is now possible to
prepare this important class of biologically active natural products in
optically pure form with anti-4,5-disubstitution.12
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