Direct boronation of allyl alcohols with diboronic acid using palladium pincer-complex catalysis. A remarkably facile allylic displacement of the hydroxy group under mild reaction conditions

Article abstract of DOI:10.1021/ja060468n

Allyl alcohols were converted to allyl boronic acids and subsequently to trifluoro(allyl)borates with tetrahydroxy diboron using palladium pincer-complex catalysis. These reactions are regio- and stereoselective proceeding with high isolated yields. Competitive boronation experiments indicate that under the applied reaction conditions the allylic displacement of a hydroxy group is faster than the displacement of an acetate leaving group. It is assumed that the hydroxy group of the allyl alcohol is converted to a diboronic acid ester functionality, which can easily be substituted. Copyright

Full text of DOI:10.1021/ja060468n

Published on Web 03/22/2006
Direct Boronation of Allyl Alcohols with Diboronic Acid Using Palladium
Pincer-Complex Catalysis. A Remarkably Facile Allylic Displacement of the
Hydroxy Group under Mild Reaction Conditions
Vilhelm J. Olsson, Sara Sebelius, Nicklas Selander, and Ka´lma´n J. Szabo´*
Department of Organic Chemistry, Stockholm UniVersity, SE-106 91 Stockholm, Sweden
Received January 20, 2006; E-mail: kalman@organ.su.se
Table 1. Palladium-Catalyzed Direct Boronation of Allyl Alcoholsa
Allyl alcohols are one of the most readily available substrates
in palladium-catalyzed allylic displacement reactions.1 Unfortu-
nately, the hydroxy group is one of the most reluctant leaving groups
in substitution reactions, and therefore, application of harsh reaction
conditions and employment of Lewis acids or other additives are
required in these processes.1c-j However, employment of these
reaction conditions and reagents precludes the efficient synthesis
of unstable allyl metal derivatives, such as allyl boronates, in high
isolated yields.
We have now found that hydroxy to boronate substitution can
be achieved under mild conditions using a wide variety of allyl
alcohols (3a-k) and diboronic acid (also called tetrahydroxydi-
boron, 2) with 5 mol % pincer-complex2 12a in a mixture of DMSO
and MeOH (eq 1). This reaction can be employed for regio- and
stereoselective synthesis of allyl boronic acids 4a-j.3a,b,4a As allyl
boronic acids are not sufficiently stable under solvent-free
conditions,3a,4a compounds 4a-j were converted3b-f,4a to their
trifluoro(allyl)borate derivatives 5a-j (Table 1), which are useful
precursors in Lewis acid and transition metal catalyzed allylation
reactions.3b,c,4d Because of the mild reaction conditions and the use
of the highly selective4 (and readily available2a) pincer-complex
catalyst 1, the isolated yields of the allyl boronate products are
very high (Table 1). Commonly used palladium(0) sources, such
as Pd2(dba)3 and Pd(PPh3)4, were found to be inefficient as catalysts
in the presented reactions.
The boronation reactions (eq 1) proceed with excellent regiose-
a Unless otherwise stated, the reactions of 2 and the corresponding
substrates were conducted in the presence of 1 (5 mol %) in a mixture of
DMSO and MeOH. After the indicated reaction times, aqueous KHF2 was
added. b Isolated yield. c Pure MeOH used as solvent. d A mixture of DMSO
and water was used as solvent. e p-Toluenesulfonic acid (2.5 mol %, entry
11, or 5 mol %, entry 10) was used as cocatalyst.
lectivity, as isomeric allyl alcohols 3a and 3b give the same
regioisomer 5a. Similarly, both branched alcohol 3c and linear
alcohol 3d provide linear allyl boronates 5b and 5c, respectively.
Unsubstituted cyclic alcohol 3f reacted smoothly, providing the
corresponding boronate 5e in excellent yield. Allylic substitution
with hydroxy or benzyloxy groups leads to increased reactivity, as
boronation of 3g-i proceeded at a temperature (20-40 °C) lower
than that of the corresponding reaction of the alkyl-substituted
analogues 3c-f (40-60 °C). The relatively low temperature is also
essential for the high isolated yields of the products since allyl
hydroxy boronates 4g,h/5g,h very easily undergo hydroxy boronate
elimination to give the corresponding 1,3-diene. Compounds 3g,h
reacted with excellent regioselectivity to give linear products 5f,g.
Interestingly, substitution of 3h resulted in monoboronated product
5g; thus the reaction can be employed for desymmetrization of
bisallyl alcohols. Using harsher reaction conditions to obtain the
diboronated product leads to extensive formation of butadiene.
Substitution of cyclic substrate 3i provides a single diastereomer
5h, indicating that the boronation reaction is both regio- and
stereoselective (entry 9).
The substitution pattern of 5h clearly shows that the reaction
proceeds with allyl rearrangement and with trans stereoselectivity.
For acyclic primary dialcohol 3h, the boronation reaction affords
the corresponding linear product 5g; however, in case of cyclic
analogue 3i, the directing effect of the hydroxy group leads to
formation of the 1,2-substituted product 5h. Formation of this
regioisomer is particularly surprising since usual palladium-
catalyzed reactions via allyl-palladium complexes bearing electron-
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C O M M U N I C A T I O N S
a methanol molecule in the six-membered ring TS (6) of the process.
In 7, the hydroxy group is converted to a better leaving group, and
moreover, the cleavage of the B-B bond is also facilitated by
coordination of the water molecule produced in the esterification.
Application of small amounts of PTS (entries 10 and 11, Figure 1)
is supposed to catalyze the ester formation.
Figure 1. Formation of 4a from 3a (b, 4) and cinnamyl acetate (0) using
2 and 5 mol % of 1 in DMSO-d6/MeOH-d4 mixture at 55 °C. Effects of
addition of 5 mol % PTS (4).
In summary, we have shown that allyl alcohols can be converted
to allyl boronates using 2 and catalytic amounts of 1. Functionalized
allyl boronates are very useful precursors in natural product and
advanced organic synthesis,3a-d,7a,b which explains the great current
interest to find efficient synthetic methods for preparation of these
species.4a,7 The above presented robust catalytic transformation
employs the least expensive allylic precursors reported for synthesis
of functionalized allyl boronates, and therefore, this method is also
a good example for the synthesis of highly value-added chemicals.
withdrawing substituents usually give the other regioisomer, the
1,4-substituted product.1a,5
In the presence of COOR groups (3j,k), the rate of boronation
reaction drops considerably. However, we found that addition of
catalytic amounts (3-5 mol %) of strong acids, such as p-toluene
sulfonic acid (PTS), considerably accelerated the conversion of 3j,k,
affording the corresponding boronated products 5i and 5j. Again
5i was obtained as a single diastereomer, clearly indicating that
the boronation reactions proceed with high trans regioselectivity.
We found that using a DMSO/MeOH mixture is indispensable
to obtain high reaction rates and high yields. When the reactions
were performed in pure DMSO, a very slow reaction with low
conversion (about 5-20%) of the allyl alcohol substrate occurred.
On the other hand, catalyst 1 is poorly soluble in pure MeOH, and
therefore, only the most reactive allyl alcohols 3h,i react under mild
conditions using MeOH as solvent (entry 8). As mentioned above,
allyl hydroxy boronates tend to decompose to 1,3-dienes. This
decomposition is particularly fast for 4h in MeOH, decreasing the
yield of the boronation reaction. We found that in a DMSO/water
mixture the rate of consumption of 3i is slower than that in MeOH;
however, the corresponding boronated product 4h/5h could be
obtained in high yield (entry 9), indicating that 4h is stable in the
presence of water as cosolvent.
Acknowledgment. This work was supported by the Swedish
Research Council (VR).
Supporting Information Available: Experimental procedures as
well as characterization and NMR spectra of the products. This material
is available free of charge via Internet at http://pubs.acs.org.
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To gain insight into the activation of the hydroxy group, we
carried out competitive boronation experiments (Figure 1) monitored
1
by H NMR. We have previously shown4a that cinnamyl acetate
and 2 in the presence of catalytic amounts of 1 afford cinnamyl
boronic acid 4a. Surprisingly, under the same reaction conditions,
cinnamyl alcohol 3a was converted significantly faster to boronic
acid 4a than was cinnamyl acetate. Thus, 3a was converted
quantitatively to 4a in 8 h, while its acetate derivative was still
present in the reaction mixture after 11 h.6 Addition of 5 mol % of
PTS had a dramatic effect on the rate of the reaction, as boronation
of 3a was complete in 2 h accounting for a 4-fold acceleration of
the reaction. Allylboronic acid 4a was surprisingly stable7b in the
presence of PTS, as in 9 h only 5% of 4a was decomposed (Figure
1).
The above studies clearly indicate that under the employed
reaction conditions the hydroxy group of the allyl alcohol is
converted to an excellent leaving group, which is easier to displace
than an acetate. A possible explanation is that 2 acts as a Lewis
acid catalyst by interacting with the free electron pairs of the oxygen
of 3a-k. A similar activation is suggested in the Tamaru reaction
employing BEt3 for activation of allyl alcohols.1c-e On the other
hand, boronic acids are far less efficient Lewis acids than are alkyl
(or halo) boranes. Therefore, we envision another type of activation
of the hydroxy group involving formation of allyl boronic acid ester
7 (eq 2). This esterification is probably facilitated by inclusion of
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