A flexible access to highly functionalised boronates

Article abstract of DOI:10.1039/b109637k

The radical addition of various xanthates to allyl or vinyl boronates occurs smoothly in the presence of a small amount of lauroyl peroxide as initiator to give good yields of usefully functionalised boronates.

Full text of DOI:10.1039/b109637k

A flexible access to highly functionalised boronates
Heraclio Lopez-Ruiz and Samir Z. Zard*
Laboratoire de Synthèse Organique associé au CNRS, Ecole Polytechnique, 91128 Palaiseau, France.
E-mail: zard@poly.polytechnique.fr; Fax: +33 (0)1 6933 3851; Tel: +33 (0)1 6933 4872
Received (in Cambridge, UK) 23rd October 2001, Accepted 6th November 2001
First published as an Advance Article on the web 30th November 2001
The radical addition of various xanthates to allyl or vinyl
boronates occurs smoothly in the presence of a small amount
of lauroyl peroxide as initiator to give good yields of usefully
functionalised boronates.
1,2-dichloroethane, a smooth reaction occured to produce
adduct 4a in high yield (Table 1).† The same transformation
could be accomplished with a number of other xanthates
containing various functional groups, including ketones, esters,
nitriles, and even heterocyclic rings, as shown by the varied
examples compiled in the Table 1. The yields have not been
optimised but nevertheless are generally quite good.
The emergence of the poweful palladium induced coupling of
boronates with halides, the Suzuki–Miyaura reaction, has
caused a renewed interest in the chemistry of boronic acid
derivatives.1 Access to boronates has so far relied heavily on
ionic and organometallic processes, with radical reactions
playing only a very minor part.2 The Kharasch addition of
halides to vinyl boronates was reported by Matteson some years
ago and has been used occasionally since.3 In one, more recent
work, simple radicals generated using stannane chemistry or
through the Barton decarboxylation were found to add to vinyl
boronates.4 Ring-closures of radicals a-to the boron atom have
also been described.5 Recent theoretical studies seem to indicate
that boronates have a much lower stabilising influence on an
adjacent radical, in comparison to boron groups with less
donating substituents.6 In the present communication, we
describe a flexible approach to functionalised boronates by
application of the xanthate transfer radical addition7 to both
allyl and vinyl boronates.
The radical addition sequence is summarised in Scheme 1 for
the case of allyl boronate 2. Thus, radical R·, generated from
xanthate 1 by the action of the initiator, undergoes addition to
the least hindered end of the terminal olefin to give a new
radical 3, which then engages in a reversible addition–
fragmentation process leading to adduct 4 with the concomitant
regeneration of radical R· to propagate the chain. Addition to
the unactivated olefinic bond is possible because R· is not
competitively consumed by reaction with xanthate 1 (this
reaction is both reversible and degenerate) and its effective
lifetime in the medium is therefore significantly increased.
Fragmentation of intermediate adduct radical 3 to give olefin 5
and high energy boryl radical 6 did not seem likely in the light
of a recent ESR study of radicals adjacent to boronates.6
Indeed, when a small amount of lauroyl peroxide was added
portion-wise to a refluxing, concentrated solution of xanthate 1a
(1 M) and a 1.5 to 2-fold excess of allyl boronate 2 in
The xanthate group in the adduct can be efficiently reduced
off either by treatment with a stoichiometric amount of lauroyl
peroxide in isopropanol,8 as illustrated by the conversion of 4e
into 7e, or by using the more traditional tributyltin hydride as in
the reduction of 4a into 7a (Scheme 2). The former, tin-free
procedure is more convenient for large scale work or for
producing samples destined for biological testing. The presence
of the xanthate group can alternatively be exploited to create
another carbon–carbon bond, for example through a ring
closure onto an aromatic ring.9 For instance, addition over a
period of one hour of a stoichiometric quantity of lauroyl
peroxide to a refluxing solution of adducts 4a or 4b in
chlorobenzene resulted in the formation of tetralones 8a and 8b
in 35 and 42% yield respectively.
Finally, by performing the first radical addition on a vinyl
boronate such as 9, the relative position of the various functions
present in the initial xanthate with respect to the boronate group
can be easily and conveniently modified. The synthesis of
compounds 10a and 10b (Scheme 3) provides two examples
where the xanthate and the boronate groups are now in a
geminal disposition.
Table 1 Synthesis of boronates 4
Xanthate 1
Boronate 4
Yield (%)
4a (94)
4b (78)
4c (78)
(63)
(85)
(68)
(70)
Scheme 1
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Chem. Commun., 2001, 2618–2619
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b109637k

2H, H arom), 4.62 (m, 2H, OCH2CH3), 4.03 (m, 1H, CHS), 3.13 (m, 2H,
CH2CH2), 2.27–2.10 (m, 2H, CH2CH2), 1.39 (t, J
= 7.2 Hz, 3H,
OCH2CH3), 1.37 (d, J = 8.1 Hz, 2H, CH2B), 1.24 ( 12H, 4CH3). 13C NMR
(75 MHz, CDCl3): 214.3, 199.4, 136.9, 133.1, 128.6, 128.2, 83.7, 69.7, 47.5,
36.2, 30.7, 24.9, 13.8. IR (cm21) n: 1686 (CNO). Anal. Calc. for
C20H29BO4S2: C, 58.82; H, 7.16. Found: C, 58.85, H, 7.16%.
(4e): 1H NMR (300 MHz, CDCl3): 4.67 (q, J = 7.2 Hz, 2H, OCH2CH3),
3.99 (m, 1H, CHS), 2.18 (t, J = 7.6 Hz, 2H, NCCH2), 2.12 (m, 2H, NCCH2
CH2), 1.43 (t, J = 7.2 Hz, 3H, OCH2CH3), 1.32 (d, J = 7.5 Hz, 2H, CH2B),
1.25 (bs, 12H, 4CH3). 13C NMR (75 MHz, CDCl3): 188.0, 119.4, 83.9, 70.1,
46.4, 32.2, 24.8, 15.1, 13.8. IR (cm21) n: 2247. Anal. Calc. for
C14H24BNO3S2: C, 51.07; H, 7.35. Found: C, 51.33, H, 7.47%.
(10b): 1H NMR (300 MHz, CDCl3): 7.95-8.10 (m, 2H, H arom), 7.1–7.25
(m, 2H, H arom), 4.55–4.70 (3H, OCH2CH3, CHS), 3.18, (t, J = 6.0 Hz, 2H,
CH2CH2), 2.15–2.37 (m, 2H, CH2CH2), 1.4 (t, J = 7.5 Hz, 3H, OCH2CH3),
1.28 (bs, 12H, 4CH3). 13C NMR (75 MHz, CDCl3): 199.5, 179.3, 136.9,
133.1, 128.6, 128.1, 84.4, 70.13, 37.3, 29.6, 24.9, 14.18. IR (cm21) n: 1684,
1598, 1226, 1050. Anal. Calc. for C19H26BFO4S2: C, 55.34; H, 6.36. Found:
C, 55.83, H, 6.07.
(7e) A solution of xanthate adduct 4e (0.23 mmol) in propan-2-ol (1 mL)
was heated to reflux for 15 min. Lauroyl peroxide (10 mol%) was then
added every 1 h until almost complete consumption of the xanthate
(100–110 mol%). The solvent was removed under reduced pressure and the
product isolated by chromatography over silica gel with heptane–ethyl
acetate (9+1). 1H NMR (300 MHz, CDCl3): 7.97 (d, J = 7.2 Hz, 1H, H
arom), 7.82 (d, J = 8.1 Hz, 1H, H arom), 7.47 (m, 1H, H arom), 7.33 (m,
1H, H arom), 3.12 (t, J = 7.5 Hz, 2H, CH2), 1.80 (m, 2H, CH2 ), 1.63 (m,
2H, BCH2), 1.26 (s, 12H, CH3) 0.90 (m, 2H, CH2). 13C NMR (75 MHz,
CDCl3): 179.0,172.7, 153.0, 125.8, 124.6, 122.4, 121.4, 83.0, 34.1, 31.9,
29.6, 24.8. Anal. Calc. for C17H24BNO2S: C, 64.36; H, 7.63. Found: C,
64.35, H, 8.21%.
Scheme 2 Reagents: (i) lauroyl peroxide (100–110 mol%) propan-2-ol,
reflux; (ii) Bu3SnH, toluene, reflux; (iii) lauroyl peroxide (100–110 mol%),
chlorobenzene, reflux.
1 (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457; (b) A. Suzuki,
J. Organomet. Chem., 1999, 576, 147.
2 (a) D. S. Matteson, Stereodirected Synthesis with Organoboranes,
Springer, Berlin, 1995; (b) D. S. Matteson, J. Organomet. Chem., 1999,
581, 51; M. Nakamura, K. Hara, T. Hatakeyama and E. Nakamura, Org.
Lett., 2001, 3, 3137 and references there cited.
3 (a) D. S. Matteson, J. Am. Chem. Soc., 1959, 81, 5004; D. S. Matteson,
J. Am. Chem. Soc., 1960, 82, 4228; (b) D. S. Matteson and J. D. Liedtke,
J. Org. Chem., 1963, 28, 1924; (c) M. Vaultier, A. El Louzi, S. Lafquih-
Titouani and M. Soufiaoui, Synlett, 1991, 267; N. Guennouni, C. Rasset-
Deloge, B. Carboni and M. Vaultier, Synlett, 1992, 581; (d) F. Lhermite
and B. Carboni, Synlett, 1996, 377.
Scheme 3
The present approach to boronates is simple, yet efficient and
flexible. A broad variety of densely functionalised, otherwise
inaccessible boronates can be rapidly prepared using cheap and
readily available starting materials and reagents.
4 N. Guennouni, F. Lhermite, S. Cochard and B. Carboni, Tetrahedron,
1995, 51, 6999.
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1996, 37, 6847; (b) R. A. Batey and D. V. Smil, Angew. Chem., Int. Ed.,
1999, 38, 1798.
6 J. C. Walton, A. J. McCarroll, Q. Chen, B. Carboni and R. Nziengui, J.
Am. Chem. Soc., 2000, 122, 5455 and references there cited.
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Sire and S. Z. Zard, Phosphorus, Sulfur Silicon, 1999, 153–154, 137.
8 A. Liard, B. Quiclet-Sire and S. Z. Zard, Tetrahedron Lett., 1996, 37,
5877.
Notes and references
† General procedure for the radical addition to allyl and vinyl boronates 2
and 9. A solution of xanthate 1 (1 mmol) and ally or vinyl boronate 2 or 9
(1.5 mmol) in 1,2-dichloroethane (ca. 1 mL) was heated to reflux for 15
min. Lauroyl peroxide (10 mmol%) was then added every 1 h until almost
complete consumption of the xanthate. The solvent was removed under
reduced pressure and the residue purified by chromatography on silica to
give the corresponding adduct 4 or 10.
1
Representative spectral and analytical data. (4a): H NMR (300 MHz,
CDCl3): 7.95 (d, J = 6.6 Hz, 2H, H arom), 7.52 (m, 1H, H arom), 7.45 (m,
9 A. Liard, B. Quiclet-Sire, R. N. Saicic and S. Z. Zard, Tetrahedron Lett.,
1997, 38, 1759.
Chem. Commun., 2001, 2618–2619
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