Platinum-catalyzed tandem diboration/asymmetric allylboration: Access to nonracemic functionalized 1,3-diols

Article abstract of DOI:10.1021/ol034936z

(Matrix presented) A single-pot tandem catalytic diene diboration/carbonyl allylation reaction is described that uses a commercially available chiral diboron reagent. The chirality of the intermediate diboration adduct is transferred to the product in the

Full text of DOI:10.1021/ol034936z

ORGANIC
LETTERS
2003
Vol. 5, No. 14
2573-2575
Platinum-Catalyzed Tandem Diboration/
Asymmetric Allylboration: Access to
Nonracemic Functionalized 1,3-Diols
Jeremy B. Morgan and James P. Morken*
Department of Chemistry, Venable and Kenan Laboratories, The UniVersity of North
Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290
morken@unc.edu
Received May 28, 2003
ABSTRACT
A single-pot tandem catalytic diene diboration/carbonyl allylation reaction is described that uses a commercially available chiral diboron
reagent. The chirality of the intermediate diboration adduct is transferred to the product in the carbonyl allylation reaction, thereby providing
access to enantioenriched chiral products. Notably, the reaction allows for construction of a quaternary stereocenter and furnishes a synthetically
versatile C−B bond in the reaction product.
Catalytic addition of metal-metal-bonded reagents to organic
substrates provides dimetallic species that are versatile
intermediates in organic synthesis. Along these lines, reagents
containing intermetallic bonds have been successfully added
across alkenes, alkynes, dienes, enones, and imines.1 Of the
processes mentioned, bis-metalation of 1,3-dienes is par-
ticularly useful since it provides access to allyl(bis)metal
species (A, Scheme 1),2 and we expected that these com-
appropriately substituted diene precursors, the allylmetalation
reaction may allow for higher product substitution and hence
allow access to quaternary stereocenters.4,5 To develop this
methodology for use in asymmetric synthesis, we have begun
to examine methods for enantiocontrol in tandem dimetala-
tion/allylation reactions. Our initial approach was to first
develop mild conditions for activation of the B-B bond in
chiral diboranes and subsequently to examine allylmetalation
reactions of the chiral allylborane reagents.
Successful development of a stereoselective tandem di-
metalation/allylation reaction requires control of selectivity
during each step of the multistep sequence. In this regard,
we were attracted to the commercially available diboron
reagent bis(diethyl-L-tartrateglycolato)diboron6 (1) due to the
Scheme 1
(2) (a) Ishiyama, T.; Masafumi, Y.; Miyaura, N. Chem. Commun. 1996,
2073. (b) Clegg, W.; Thorsten, J.; Marder, T. B.; Norman, N. C.; Orpen,
A. G.; Peakman, T. M.; Quayle, M. J.; Rice, C. R.; Scott, A. J. J. Chem.
Soc., Dalton Trans. 1998, 1431.
(3) For diastereoselective diboration/allylboration, see: (a) Suginome,
M.; Nakamura, H.; Matsuda, T.; Ito, Y. J. Am. Chem. Soc. 1998, 120, 4248.
(b) Suginome, M.; Matsuda, T.; Yoshimoto, T.; Ito, Y. Org. Lett. 1999, 1,
1567.
(4) For approaches to the construction of quaternary stereocenters, see:
(a) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388.
(b) Christoffers, J.; Mann, A. Angew, Chem. Int. Ed. 2001, 40, 4591.
(5) For asymmetric allylmetalation reactions that generate quaternary
stereocenters, see: (a) Yamamoto, Y.; Hara, S.; Suzuki, A. Synlett 1996,
883. (b) Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488. (c)
Kennedy, J. W.; Hall, D. G. J. Am. Chem. Soc. 2002, 124, 898.
pounds may participate in subsequent cascade reactions. As
an example (Scheme 1), the allyl(bis)metallic species may
engage in a carbonyl addition reaction, the product of which
(B) may then react with a second reagent (to give C).3 With
(1) For reviews with representative reactions, see: (a) Marder, T. B.;
Norman, N. C. Top. Catal. 1998, 5, 63. (b) Suginome, M.; Ito, Y. Chem.
ReV. 2000, 100, 3221. (c) Ishiyama, T.; Miyaura, N. J. Organomet. Chem.
2000, 611, 392.
10.1021/ol034936z CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/13/2003

known ability of the tartrate control element to effectively
influence stereoselection in the allylmetalation reaction.7 We
have found that under appropriate conditions, (Z)-selective
1,4-addition across 1,3-dienes occurs. Subsequently, we
surveyed the ability of the resulting bis-boronates to engage
in stereoselective allylmetalation reactions. The resulting
allylation product may be manipulated in situ, and the one-
pot process from diene to product is the subject of this report.
The majority of diboration reactions described in the
literature are catalyzed by phosphine-containing platinum-
(0) metal centers. The proposed mechanism for the diboration
of 1,3-dienes involves initial oxidative addition of the
diborane to furnish a square-planar L2PtB2 intermediate.2b,8
Since dissociation of a phosphine ligand from the L2PtB2
center is required for coordination of the reacting diene, we
expected that a platinum catalyst with a monodentate phos-
phine would be most active. Addition of 1 to 2,3-dimeth-
ylbutadiene was examined with the readily available complex
Pt(dba)2 (Scheme 2).9 Reactions were carried out in C6D6 at
product was obtained cleanly after oxidative workup (Scheme
3). The corresponding 1,3-diol that contains a quaternary
Scheme 3
carbon stereocenter was isolated in 72% yield and >19:1
syn:anti diastereoselection with the syn isomer being formed
in 74% enantiomeric ratio.
In an effort to improve the reaction selectivity, the effect
of tartrate structure on enantioselection was investigated
(Table 1). Though a linear correlation between selectivity
Table 1. Catalytic Diboration/Allylation with Chiral
Diboronatesa
Scheme 2
entry
tartrate (R)
% yield
% ee
1
2
3
4
Me
Et
i-Pr
CH(i-Pr)2
21
68
38
17
72
74
58
60
1
room temperature and followed by in situ H NMR spec-
troscopy. While diene diboration did not proceed well at
room temperature in the absence of ligand or in the presence
of triphenylphosphine (<10% conversion), addition of 1
equiv of tricyclohexylphosphine relative to platinum resulted
in >95% conversion to the diboration adduct after 14 h.
Notably, the reaction with PCy3 provided the required high
levels of stereocontrol furnishing a >20:1 Z:E ratio of
stereoisomers.10
Since tartrate boronate esters suffer hydrolytic cleavage
in the presence of water, the diboration adducts were em-
ployed without isolation. The benzene solution obtained from
the stereoselective diboration was therefore diluted with 3
parts toluene, and 4 Å powdered molecular sieves were
added. Upon dropwise addition of a cyclohexane carboxal-
dehyde solution at -78 °C, the corresponding allylation
a Step 1: 1 equiv of diene, 1 equiv of diboronate, benzene, rt, 12 h.
Step 2: toluene, 4 Å mol sieves, 1 equiv of RCHO -78 °C, 3 h. Step 3:
50 °C, 3 h. For all reactions, syn:anti > 19:1.
and steric encumbrance is not observed, a steric component
is obvious. The sterically less bulky dimethyl tartrate-derived
boronate provides enantioselection on the order of that seen
for diethyl tartrate. However, increasing the size of the R
group to isopropyl or 2,4-dimethylpentyl (entries 3 and 4)
leads to a decrease in the enantiomeric ratio and the reaction
yield.11 Reaction with tartrate amides and with amino
alcohol-derived diboranes failed in the initial diboration
reaction (data not shown).
Examination of a series of substrates suggests that the cis-
diboration adduct leads to exclusive formation of the syn
allylation adduct (>19:1 syn/anti ratio in all cases, Table
2). Yields are good to excellent for the three-step procedure
regardless of substrate structure, although the enantiomeric
ratio is strongly substrate dependent. Aliphatic aldehydes
provide the highest enantioselectivities (entries 1-3 and 6),
whereas aromatic and R,â-unsaturated aldehydes provide
(6) Commerically available from Aldrich Chemical Co.
(7) (a) Roush, W. R.; Walts, A. E.; Hoong, L. K. J. Am. Chem. Soc.
1985, 107, 8186. (b) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz,
A. D.; Halterman, R. L. J. Am. Chem. Soc. 1990, 112, 6339. (c) Roush, W.
R.; Hoong, L. K.; Palmer, M.; Park, J. C. J. Org. Chem. 1990, 55, 4109.
(8) For investigations on the mechanism of alkyne diboration, see:
Iverson, C. N.; Smith, M. R. Organometallics 1996, 15, 5155.
(9) Cherwinski, W. J.; Johnson B.; Lewis, J. J. Chem. Soc., Dalton Trans.
1974, 1405.
(10) For the ability of basic monophosphines to promote alkyne
diboration, see: Thomas, R. L.; Souza, F.; Marder, T. B. J. Chem. Soc.,
Dalton Trans. 2001, 1650.
(11) Beneficial effect of larger tartrate substituents in allylation reac-
tions: Hara, S.; Yamamoto, Y.; Fujita, A.; Suzuki, A. Synlett 1994, 639.
2574
Org. Lett., Vol. 5, No. 14, 2003

Roush with simple allylboronates, and it provided the highly
oxygenated product in excellent yield and as a single
stereoisomer by 1H NMR. The opposite enantiomer of
substrate 2 leads to a 1:1 mixture of stereoisomers.
Table 2. Catalytic Diboration/Allylation of Various Aldehydes
Employing Diboronate 1a
The reactions described above were all subjected to
oxidative workup such that the remaining C-B bond in the
allylation adduct was converted to the derived alcohol. The
utility of C-B bonds in organic synthesis suggested that
other transformations might provide access to alternate
reaction products. While direct homologation of the tartrate
boronate ester was unsuccessful, homologation could be
accomplished if the allylation product was first converted
to the derived cyclic half-ester (3, Scheme 5). This trans-
Scheme 5
(a) Step 1: 1 equiv of diene, 1 equiv of 1, benzene, rt, 12 h. Step 2:
Add toluene, 4 Å mol sieves, 1 equiv of aldehyde, -78 °C, 3 h. Step 3: 50
°C, 3 h. All reaction >19:1 syn:anti. (b) Same procedure except that 5%
(PPh3)2Pt(ethylene) was used for 24 h at 80 °C in step 1.
products with lower enantioselection. In contrast to reactions
with 2,3-dimethylbutadiene, reactions with nonsymmetric
isoprene face an issue involving regioselection (entry 6).
Complete regiocontrol and diastereocontrol is observed in
this transformation such that the resulting 1,3-diol product
contains minimal substitution at the allylic stereocenter.
Given the propensity for chiral allyboronate reagents to
exhibit matched and mismatched stereoselection in allylation
reactions, we examined the influence of preexisting stereo-
centers on reaction outcome.7 After standard diboration of
2,3-dimethylbutadiene, subsequent allyl addition proceeded
smoothly with both enantiomers of aldehyde 2 (Scheme 4).
The matched enantiomer is the same as that observed by
formation occurs by direct addition of water to the allylation
product, although 3 could be obtained in higher yields if it
was subjected to dimethyl zinc prior to addition of water.
Homologation of 3 to give 4 is accomplished by addition of
chloromethyllithium according to the procedure developed
by Matteson,12 followed by oxidative workup.
In conclusion, we have developed a method that allows
access to stereodefined quaternary carbon centers from com-
mercially available starting materials. With the correct choice
of aldehyde and diboronate, versatile synthetic intermediates
may be accessed with a useful level of stereoisomeric purity.
Efforts directed toward alternate functionalization of the
intermediate alkylboronate and toward the development of
catalytic asymmetric dimetalation reactions continue in our
labs.
Scheme 4
Acknowledgment. J.B.M. is appreciative of a fellowship
from the Wellcome Trust. This work was supported by the
NIH (GM 59417-03). J.P.M. thanks AstraZeneca, Bristol-
Myers Squib, Dow, DuPont, GlaxoSmithKline, and the
Packard Foundation for support.
Supporting Information Available: Characterization
data for all new compounds and experimental procedures.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL034936Z
(12) Sadha, K. M.; Matteson, D. S. Organometallics 1985, 4, 1687.
Org. Lett., Vol. 5, No. 14, 2003
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