TEMPO-induced generation of alkyl radicals from B-alkylcatecholboranes

Article abstract of DOI:10.1055/s-1999-2718

B-alkylcatecholboranes react efficiently with 2,2,6,6- tetramethylpiperidine-N-oxyl (TEMPO) to give alkyl radicals. In the presence of an excess of TEMPO, the generated radicals are efficiently convened to alkoxyamine derivatives.

Full text of DOI:10.1055/s-1999-2718

LETTER
807
TEMPO-Induced Generation of Alkyl Radicals from B-Alkylcatecholboranes
Cyril Ollivier, Rachel Chuard, Philippe Renaud*
Université de Fribourg, Institut de Chimie Organique, Pérolles, CH-1700 Fribourg, Switzerland
E-mail: philippe.renaud@unifr.ch
Received 23 March 1999
oxy radicals should offer similar opportunities to perform
Abstract: B-alkylcatecholboranes react efficiently with 2,2,6,6-tet-
radical substitution at boron with formation of alkyl radi-
ramethylpiperidine-N-oxyl (TEMPO) to give alkyl radicals. In the
8
cals. In this communication, we report that 2,2,6,6-tet-
presence of an excess of TEMPO, the generated radicals are effi-
ramethylpiperidine-N-oxyl (TEMPO) reacts cleanly with
B-alkylcatecholboranes to afford alkyl radicals (equation
3) which can be trapped by a second equivalent of TEM-
ciently converted to alkoxyamine derivatives.
Key words: alkyl radical, alkoxyamine, alkyl-catecholborane
9
PO to give alkoxyamines (equation 4).
B-alkylcatecholboranes were prepared by hydroboration
of the corresponding alkenes 1a-e with catecholborane (2
equivalents) in the presence of a catalytic amount of N,N-
Boron chemistry represents a unique and highly versatile
tool for transformations of organic molecules. The use of
1
organoboranes as radical precursors has been reported in
10
2-3
dimethylacetamide in dichloromethane. The excess of
the early seventies by Brown. However, this work has
catecholborane was solvolyzed with 1.2 equivalent of eth-
anol. DMPU (1 equivalent) was then added followed by
2.2 equivalents of TEMPO. This one-pot procedure fur-
nished the alkoxyamines 2a-e in good yields (equation 5).
The role of DMPU is not yet understood, but in the ab-
sence of DMPU, a decrease of the yields was observed;
for instance, 1a was converted to 2a in only 63% yield. A
similar but more pronounced effect was already observed
not found many synthetic applications except for the sys-
tem Et3B/O2 that is routinely used for the initiation of rad-
ical reactions. Recently, we have reported that B-
4-6
alkylcatecholboranes are efficient radical precursors
which can be applied for radical mediated conjugate addi-
tion with various a,b-unsaturated ketones and aldehydes
7
(equation 1). The key step in the propagation of the chain
reaction was the reaction between the enolate radical and
the B-alkylcatecholborane (equation 2). Other types of
7
in the oxygen initiated reaction depicted in equation 1.
It is also important to note that this reaction works effi-
ciently with B-alkylcatecholboranes but not with trialkyl-
boranes. For instance, under similar reaction conditions
(with and without DMPU), triethylborane gave no trace of
1-ethoxy-2,2,6,6-tetramethylpiperidine. The exact reason
for this considerable difference of reactivity is not under-
stood at the moment.
Synlett 1999, No. 6, 807–809 ISSN 0936-5214 © Thieme Stuttgart · New York

808
C. Ollivier et al.
LETTER
Table 1. Hydroboration of alkenes 1a-e followed by reaction with
TEMPO according to equation 5 (NC9H18 = 2,2,6,6-tetramethylpipe-
ridin-1-yl).
Acknowledgement
We thank the "Fonds National Suisse de la Recherche Scientifique”
for financial support and Professor Rebecca Braslau for communi-
cation of preliminary results.
References and Notes
(1) Reviews on organoboranes: Brown, H. C. In Hydroboration,
2nd printing with Nobel Lecture; Benjamin-Cumming:
Reading, 1980. Brown, H. C. In Boranes in Organic
Chemistry; Cornell University Press: Ithaca, 1972. Brown, H.
C.; Kramer, G. W.; Levy, A. B.; Midland, M. M. In Organic
Synthesis via Boranes; Wiley: New York, 1975. Pelter, A.;
Smith, K. In Comprehensive Organic Chemistry, Vol. 3;
Barton, D. H. R., Ollis, W. D. Eds; Pergamon Press: Oxford,
1979, p 689. Brown H. C.; Smith, K. in Kirk-Othmer
Encyclopaedia of Chemical Technology, 3rd ed. Vol. 12;
Wiley: New York, 1980, p 793. Pelter, A.; Smith, K. and
Brown H. C. In Borane Reagents; Academic Press: London,
1988. Matteson, D. S. Stereodirected Synthesis with
Organoboranes; Springer: Berlin, 1995.
(2) Brown, H. C.; Kabalka, G. W. J. Am. Chem. Soc. 1970, 92,
714. Brown, H. C.; Negishi, E. J. Am. Chem. Soc. 1971, 93,
3777.
(3) For review articles, see: Brown, H. C.; Midland, M. M.
Angew. Chem. Int. Ed. Engl. 1972, 11, 692. Ghosez, A.; Giese,
B.; Zipse, H. in Houben-Weyl, 4th ed., Vol. E19a; Regitz, M.,
Giese, B., Eds.; p 753.
(4) Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987,
109, 2547.
(5) Formation of boron enolates from the reaction of enolate
radicals with triethylborane has been reported: Nozaki, K.;
Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn. 1991, 64, 403.
(6) Miura, K.; Ichinose, Y.; Nozaki, K.; Fugami, K.; Oshima, K.;
Utimoto, K. Bull. Chem. Soc. Jpn. 1989, 62, 143.
(7) Ollivier, C.; Renaud, P. Chem. Eur. J. 1999, 5, in press.
(8) Recently, radical chain reactions involving alkylboranes and
heteroatom centered radicals have been reported: N-centered
radicals: Miyabe, H.; Ushiro, C.; Naito, T. Chem. Commun.
1997, 1789; Miyabe, H.; Shibata, R.; Ushiro, C.; Naito, T.
Tetrahedron Lett. 1998, 39, 631; Bertrand, M. P.; Feray, L.;
Nouguier, R.; Stella, L. Synlett 1998, 780; Miyabe, H.;
Yoshioka, N.; Ueda, M.; Naito, T. J. Chem. Soc. Perkin Trans.
1 1998, 3659. O-centered radicals: Brown, H. C.; Midland, M.
M. Angew. Chem. Int. Ed. Engl. 1972, 11, 692; Nozaki, K.;
Oshima, K. Chem. Commun. 1998, 3659; Utimoto, K. Bull.
Chem. Soc. Jpn. 1991, 64, 403; Clive, D. L. J.; Postema, M. H.
D. J. Chem. Soc., Chem. Commun. 1993, 429; Devin, P.;
Fensterbank, L.; Malacria, M. Tetrahedron Lett. 1998, 39,
833.
Moderate to good yields were obtained depending on the
nature of the radical. The best yields have been obtained
with secondary alkyl radicals generated from cyclohex-
ene, 1-phenylcyclopentene and a-pinene (entries 1-3).
Primary and tertiary alkylcatecholboranes generated from
b-pinene and 2,3-dimethyl-2-butene afforded the corre-
sponding alkoxyamines with slightly lower yields (entries
4 and 5). The stereochemical outcome fits the expectation
for radical reactions: radicals react from the less hindered
face leading to trans compounds (table 1, entries 2 and
11
3).
The radical nature of the reaction was demonstrated by the
reaction of (+)-2-carene (equation 6). The intermediate
cyclopropylmethyl radical undergoes a ring opening to a
homoallyl radical. The resulting alkoxyamine was re-
duced with Zn/AcOH to afford the corresponding alcohol
12,13
in excellent yield.
(9) For the coupling reaction of alkyl radicals with aminoxyl
radicals, see: Kinney, R. J.; Jones, W. D. J.; Bergman, R. G. J.
Am. Chem. Soc. 1978, 100, 7902. Pattenden, G. Chem. Soc.
Rev. 1988, 17, 361. Howel, A. R.; Pattenden, G. J. Chem. Soc.,
Chem. Commun. 1990, 103. Patel, V. F.; Pattenden, G.;
Thompson, D. M. J. Chem. Soc. Perkin Trans. 1 1990, 2729.
Ali, A.; Harrowven, D. C.; Pattenden, G. Tetrahedron Lett.
1992, 33, 2851. Barrett, A. G. M.; Bezuidenhoudt, B. C. B.;
Melcher, L. M. J. Org. Chem. 1990, 55, 5196. Barrett, A. G.
M.; Rys, D. J. J. Chem. Soc., Chem. Commun. 1994, 837.
Hartung, J.; Giese, B. Chem. Ber. 1991, 124, 387. Boger, D.
L.; McKie, J. A. J. Org. Chem. 1995, 60, 1271. Nagashima,
T.; Curran, D. P. Synlett 1996, 330. Braslau, R.; Burrill, L. C.;
Mahal, L. K.; Wedeking, T. Angew. Chem. Int. Ed. 1997, 36,
237. Braslau, R.; Burrill, L. C.; Chaplinski, V.; Howden, R.;
Papa, P. W. Tetrahedron Asymmetry 1997, 8, 3209. Braslau,
In summary, we reported an alternative method to gener-
ate alkyl radicals from B-alkylcatecholboranes. Further
investigations to demonstrate the utility of this approach
to run inter- and intramolecular carbon-carbon bond form-
ing reactions is underway in our laboratory. Moreover,
this procedure constitutes an alternative way to oxidize or-
ganoboranes to alcohols under weakly acidic and reduc-
tive conditions. Finally, the use of optically active
14
nitroxides should broaden the scope of the radical asym-
9
metric hydroxylation procedure developed by Braslau.
Synlett 1999, No. 6, 807–809 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
TEMPO-Induced Generation of Alkyl Radicals from B-Alkylcatecholboranes
809
R.; Chaplinski, V.; Goodson, P. J. Org. Chem. 1998, 63, 9857.
Jahn, U. J. Org. Chem. 1998, 63, 7130.
(10) Garrett, C. E.; Fu, G. C. J. Org. Chem. 1996, 61, 3224.
(11) Giese, B. Angew. Chem. Int. Ed. Engl. 1989, 28, 969.
(12) Shishido, Y.; Kibayashi, C. J. Org. Chem. 1992, 57, 2876.
(13) Typical experimental procedures:
1.61 (m, 2 H); 2.20-2.14 (m, 1 H); 2.56-2.51 (m, 1 H); 5.70-
5.65 (m, 1 H, C=CH); 5.79-5.75 (m, 1 H, C=CH). 13C-NMR
(50 MHz, CDCl3): 17.2, 20.5, 20.9 (2 CH3), 21.1, 23.6, 23.8,
28.8, 29.2, 34.9, 35.2, 41.0 (2 CH2), 47.0, 59.3 (2 C), 80.9,
128.6, 133.8. Anal. C19H35NO (293.49): calcd: C 77.76, H
12.02, N 4.77; found: C 77.95, H 12.12, N 4.66.
2,2,6,6-Tetramethyl-1-{1-methyl-1-[(1R,4S)-4-methyl-2-
cyclohexen1-yl]ethoxy}piperidine (3). Catecholborane (0.64
ml, 6.0 mmol) was added dropwise at 0 °C under N2 to a soln.
of (+)-2-carene (409 mg, 3.0 mmol) and N,N-
2-[(1R,4S)-4-methyl-2-cyclohexen-1-yl]-2-propanol (4).
Reduction of the alkoxyamine 3 (147 mg, 0.50 mmol) with
Zn/AcOH according to the procedure of Kibayashi12 afforded
the alcohol 4 (63 mg, 82%) as a colorless liquid. [a]D21 = –74°
(c = 0.75, C6H6), ref 15: [a]D21 = –47.3 (c = 0.54, C6H6). 1H-
NMR (360 MHz, CDCl3): 0.98 (d, J = 7.3, 3 H); 1.18 (s, 3 H);
1.22 (s, 3 H); 1.53-1.43 (m, 2 H); 1.75-1.60 (m, 2 H); 2.13-
2.08 (m, 1 H); 2.21-2.16 (m, 1 H); 5.71-5.67 (m, 1 H); 5.79-
5.74 (m, 1 H). Anal. C10H18O (154.25): calcd: C 77.87, H
11.76; found: C 77.39, H 11.60.
dimethylacetamide (28.0 ml, 0.3 mmol) in CH2Cl2 (2.0 ml),
and the reaction mixture was heated under reflux for 3 h.
EtOH (0.21 ml, 3.6 mmol) was added at 0 °C and the soln. was
stirred for 15 min at rt. To this solution, TEMPO (1.03 g, 6.6
mmol) in CH2Cl2 (4 ml) and DMPU (0.36 ml, 3.0 mmol),
were successively added. The reaction was stirred overnight at
rt. The resulting mixture was treated with sat. NaHCO3 (10
ml) and extracted with Et2O (3 x 20 ml). The organic layer was
dried (MgSO4), filtered and concentrated. The crude product
was purified by flash chromatography (hexane, hexane/Et2O
95:5) to afford 3 (552 mg, 63%) as a colorless oil. [a]D21 = –
49.8° (c = 0.54, C6H6). 1H-NMR (360 MHz, CDCl3): 0.98 (d,
J = 7, CH3CH); 1.09, 1.10 (2s, 2 CH3); 1.12 (s, 2 CH3); 1.19,
1.21 (2s, 2 CH3); 1.31-1.25 (m, 2 H); 1.59-1.43 (m, 6 H); 1.75-
(14) For a review: Naik, N.; Braslau, R. Tetrahedron 1998, 54,
667.
(15) Cocker, W.; Hanna, D. P.; Shannon, P. V. R. J. Chem. Soc. C.
1969, 1302.
Article Identifier:
1437-2096,E;1999,0,06,0807,0809,ftx,en;G10499ST.pdf
Synlett 1999, No. 6, 807–809 ISSN 0936-5214 © Thieme Stuttgart · New York