Metal-catalysed multiple boration of ketimines

Article abstract of DOI:10.1039/a805792c

Metal-catalysed addition of B₂cat′₂ (cat′ = 4-Bu^t-1,2-O₂C₆H₃) to ketimines affords N-borylenamines and HBcat′. Analogous catalysed reactions of ketimines with HBcat′ in tetrahydrofuran affo

Full text of DOI:10.1039/a805792c

Metal-catalysed multiple boration of ketimines†
Thomas M. Cameron,a R. Tom Baker*a and Stephen A. Westcott*b
a Chemical Science and Technology Division, Los Alamos National Laboratory, MS J514, Los Alamos, NM 87545,
USA. E-mail: weg@lanl.gov
b Department of Chemistry, Mount Allison University, Sackville, NB E4L 1G8, Canada. E-mail: swestcott@mta.ca
Received (in Bloomington, IN, USA) 24th July 1998, Accepted 17th September 1998
Metal-catalysed addition of B2catA2 (catA
=
4-But-
= dibenzylidene acetone) gave primarily 2a and HBcatA, as the
resulting Pt complex is less effective in catalysing the
competitive hydroboration of 1a. Variation of the steric and
electronic properties of the ketimine had a nominal effect on the
product distribution as analogous reactions with a variety of
ketimines 1b–e gave similar results, as determined by NMR
spectroscopy.‡
1,2-O2C6H3) to ketimines affords N-borylenamines and
HBcatA. Analogous catalysed reactions of ketimines with
HBcatA in tetrahydrofuran afford multiply borated products,
providing the first examples of metal-catalysed hydro-
boration of enamines.
Transition metal catalysed diboration of alkenes and alkynes is
receiving considerable attention as a convenient and efficient
method of generating alkyl- and alkenyl-boronic esters with
well defined selectivities.1 These compounds are valuable
substrates for Suzuki coupling,2 and new developments in this
field include the direct synthesis of arylboronic esters from the
corresponding aryl halides using diboron compounds3 or
dialkoxyboranes.4 To date, catalysed diborations have been
restricted to functionalizing unsaturated hydrocarbons, with the
exception of a recent report by Marder and coworkers
describing the 1,4-diboration of a,b-unsaturated ketones.5 Our
interest in aminoboron chemistry prompted us to investigate the
diboration of imines. Transition metals can be used to catalyse
the hydroboration of imines6 and we recently found that the
corresponding diboration of aldimines provides a direct route to
the potent enzyme inhibitors, a-aminoboronic acids.7,8 In this
report we describe the versatility of metal-catalysed boron
additions to ketimines which give a variety of novel aminobor-
onate esters and provide the first examples of metal-catalysed
enamine hydroboration.
Reaction of acetophenone-derived imine, PhNNC(CH3)Ph
1a, with B2catA2 (catA = 4-But-1,2-O2C6H3) did not proceed
without a catalyst, even at elevated temperatures (90 °C for 1
week).9 Using 2 mol% RhCl(PPh3)3 at 25 °C, the reaction
produced equal amounts of N-borylenamine 2a and N-bor-
ylamine 3a, as ascertained by NMR spectroscopy.10 These
products arise presumably from initial oxidative addition of the
diboron compound to the metal center, followed by coordina-
tion of the ketimine with subsequent regioselective insertion
into the M–B bond. Finally, b-H elimination generates N-
borylenamine 2a and 1 equiv. of HBcatA which can subse-
quently add to unreacted 1a to give 3a (Scheme 1). Similar
boration reactions have been observed previously in analogous
diboration1c and hydroboration11 reactions of alkenes. Ketimine
diborations carried out using a catalytic amount of Pt(dba)2 (dba
R
Ar
1a
1b
1c
H
H
H
Ph
Ar
C6H4CF3-p
C6H4OMe-o
N
R
1d Ph C6H4OMe-p
1e Me C6H4CF3-p
Ph
In order to obtain evidence for the mechanistic pathway
discussed above, we examined the stoichiometric reaction of the
unsaturated bis(boryl) complex RhCl(BcatA)2(PPh3)2 (generated
in situ from RhCl(PPh3)3 and B2catA2) with ketimine 1a and
observed
quantitative
formation
of
dihydride
RhH2Cl(PPh3)311a,12 along with 2 equiv. of N-borylenamine 2a.
This surprising result suggests that intermediate RhHCl-
(BcatA)(PPh3)2,13 arising from the boration step, reacts with 1a
to give 2a at a comparable rate to that of the bis(boryl) complex.
Previous theoretical studies of metal-catalysed hydroboration
indicated that alkene insertion into both M–H and M–B bonds
is energetically feasible.14 Our observation of quantitative
formation of N-borylenamine indicates that only insertion of
ketimine into the M–B bond results in product formation.
These intriguing results prompted us to investigate the metal-
catalysed hydroboration of ketimines. Uncatalysed addition of
HBcatA to 1a in toluene, THF, or chloroform proceeds slowly
(days) at 25 °C to give 3a.15 Using 2 mol% RhCl(PPh3)3 in
toluene, however, gave a mixture of 2a and 3a along with a
small amount of the 1,3-diboration product, catABN-
(Ph)CH(Ph)CH2BcatA 4a, derived from an unprecedented
catalysed hydroboration of enamine 2a. Remarkably, reactions
carried out in CDCl3 gave predominantly hydroborated keti-
mine 3a, while those in THF afforded predominantly 4a and the
1,1,3-triboration product, catABN(Ph)CH(Ph)CH(BcatA)2 5a in a
3:1 ratio.‡ The 4a:5a ratio determined by 1H NMR was
confirmed by hydrolysis, which gives elimination products
styrene and E-vinylboronate ester,1a respectively.16
[M] + cat'B-Bcat'
1a
Several reactivity trends were observed in the catalysed
hydroborations of substituted ketimines.‡ Reaction of the
electron poor ketimine, (p-CF3C6H4)NNC(CH3)Ph 1b, with
HBcatA in THF gave more rapid conversion (cf. 1a) of the
intermediate enamine and afforded analogous multiply borated
amines 4b and 5b in a 5:1 ratio. The sterically hindered,
electron-rich ketimine, (o-MeOC6H4)NNC(CH3)Ph 1c, on the
other hand, gave primarily enamine 2c and amine 3c. Deoxy-
benzoin-derived imine, (p-MeOC6H4)NNC(CH2Ph)Ph 1d, gave
both E- and Z-enamines and only one isomer was hydroborated
to a single diastereomer of the 1,3 diboration product 4d. Steric
hindrance also precludes formation of the triborated product and
gives rise to Rh-mediated HBcatA degradation leading to minor
cat'B
Ph
Ph
Bcat'
[M]
Bcat'
Ph
CH3
Ph
Bcat'
N
+
H
[M]
Bcat'
[M]
N
N
Ph
Bcat'
Ph
CH3
2a
[M] + HBcat'
Ph
1a
cat'B
N
Ph
CH3
3a
Scheme 1
Chem. Commun., 1998, 2395–2396
2395

3a:4a:5a
= 3:6:2; 2b:3b:4b:5b = 1:8:12:2; 2c:3c:4c:5c =
6:8:2:1; 2d:3d:4d = 2:5:1; 2e:3e:4e = 4:4:1.
1 (a) R. T. Baker, J. C. Calabrese, S. A. Westcott, P. Nguyen and T. B.
Marder, J. Am. Chem. Soc., 1993, 115, 4367; (b) T. Ishiyama, N.
Matsuda, N. Miyaura and A. Suzuki, J. Am. Chem. Soc., 1993, 115,
11 018; (c) R. T. Baker, P. Nguyen, T. B. Marder and S. A. Westcott,
Angew. Chem., Int. Ed. Engl., 1995, 34, 1336; (d) C. N. Iverson and
M. R. Smith, III, J. Am. Chem. Soc., 1995, 117, 4403; (e) G. Lesley, P.
Nguyen, N. J. Taylor, T. B. Marder, A. J. Scott, W. Clegg and N. C.
Norman, Organometallics, 1996, 15, 5137; (f) C. N. Iverson and M. R.
Smith, III, Organometallics, 1996, 15, 5155; (g) T. Ishiyama, M.
Yamamoto and N. Miyaura, Chem. Commun., 1996, 2073; (h) C. N.
Iverson and M. R. Smith, III, Organometallics, 1997, 16, 2757; (i) T.
Ishiyama, M. Yamamoto and N. Miyaura, Chem. Commun., 1997, 689;
(j) T. Ishiyama, T. Kitano and N. Miyaura, Tetrahedron Lett., 1998, 39,
2357; (k) Q. Cui, D. G. Musaev and K. Morokuma, Organometallics,
1997, 16, 1355; 1998, 17, 742.
2 S. D. Brown and R. W. Armstrong, J. Org. Chem., 1997, 62, 6076; N.
Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457.
3 T. Ishiyama, M. Murata and N. Miyaura, J. Org. Chem., 1995, 60,
7508.
4 M. Murata, S. Watanabe and Y. Masuda, J. Org. Chem., 1997, 62,
6458.
5 Y. G. Lawson, M. J. G. Lesley, T. B. Marder, N. C. Norman and C. R.
Rice, Chem. Commun., 1997, 2051.
6 R. T. Baker, J. C. Calabrese and S. A. Westcott, J. Organomet. Chem.,
1995, 498, 109.
7 S. J. Coutts, T. A. Kelly, R. J. Snow, C. A. Kennedy, R. W. Barton, J.
Adams, D. A. Krolikowski, D. M. Freeman, S. J. Campbell, J. F.
Ksiazek and W. W. Bachovchin, J. Med. Chem., 1996, 39, 2087; V.
Martichonok and J. B. Jones, J. Am. Chem. Soc., 1996, 118, 950; P. K.
Jadhav and H.-W. Man, J. Org. Chem., 1996, 61, 7951.
Scheme 2
8 Metal-catalysed 1,2-diboration of aldimines will be described else-
where: R. T. Baker, T. M. Cameron and S. A. Westcott, manuscript in
preparation.
9 Uncatalysed addition of diboron compounds to aldimines gives
stereoselective coupling to C2-symmetric N-boryldiamines: R. T. Baker,
T. M. Cameron and S. A. Westcott, unpublished results.
amounts of aminoborane side-products derived from ‘BH3’
addition.11a Propiophenone-derived imine, (p-CF3C6H4)-
NNC(CH2CH3)Ph 1e, is readily converted to isomeric N-
borylenamines, but subsequent catalysed hydroboration is
accompanied by significant HBcatA degradation.
10 NMR data in [2H8]THF: 2a: 1H, d 7.6–6.8 (ov m, Ph + catA, 13H), 5.73,
5.42 (s, NCH2), 1.30 (9H, But); 13C, d 148.3 (CNCH2), 149.4, 147.2,
146.4, 144.8, 138.4 (ipso of CPh, NPh, and catA), 129.4, 129.0, 127.5,
123.4 (o-, m-C of NPh and CPh), 128.9, 124.1 (p-C of NPh and CPh),
119.3, 111.4, 110.2 (catA), 112.5 (NCH2), 35.4 (But C), 32.1 (ButCH3).
11B (90 °C), d 23.5. 3a: 1H, d 7.6–6.9 (ov m, Ph + catA, 13H), 5.19 (q, J
7, Hz, CHPh), 1.64 (d, J 7 Hz, 3H, CH3), 1.29 (9H, But); 13C, d 149.6,
147.5, 146.1, 144.6, 143.6 (ipso-C of CPh, NPh and catA), 129.2, 129.0,
128.9, 127.9 (o-, m-C of NPh and CPh), 127.7, 126.2 (p-C of NPh and
CPh), 118.9, 111.1, 109.8 (catA), 58.4 (CN), 35.3 (But C), 32.1 (But
CH3), 20.0 (CH3); 11B (90 °C), d 26.3. 4a: 1H, d 7.5–6.8 (ov m, Ph + catA,
16H), 5.59 (‘tr’, J 8 Hz, CHPh), 2.25 (dd, J 16, 8.5 Hz, CH2B), 2.12 (dd,
J 16, 8 Hz, CH2B), 1.30 (9H, But of NBcatA), 1.27 (9H, But of CBcatA);
13C, d 149.6, 149.2, 147.5, 147.0, 146.9, 146.0, 144.6, 143.5 (ipso-C of
CPh, NPh, NBcatA and CBcatA), 129.5, 129.2, 129.0, 128.1, (o-, m-C of
NPh and CPh), 127.9, 126.5 (p-C of NPh and CPh), 119.9, 118.9, 111.8,
111.1, 110.3, 109.8 (catA), 60.1 (CN), 35.4, 35.3 (But C), 32.1 (ov, 6C,
But CH3), 17.8 (br, CB); 11B (90 °C), d 35.7 (BC), 20.3 (BN). 5a: 1H,
d 7.6–6.9 (ov m, Ph + catA, 19H), 6.06 (d, J 13 Hz, CHPh), 3.17 (d, J 13
Hz, CHB2), 1.32 (9H, But of NBcatA), 1.26, 1.25 (9H, But of CBcatA);
13C, d 62.2 (CN), 18.1 (br, CB).
We propose that formation of the multiply borated products is
due to competitive insertion of enamine 2 into M–H and M–B
bonds to give 4 and N,C-diborylenamine 6; the latter is
subsequently hydroborated to 5 (Scheme 2). The enamine
hydroboration/boration ratio depends on the substrate, solvent,
and catalyst, and further catalyst development is ongoing.
In summary, we have shown that metal-catalysed diboration
of ketimines affords N-borylenamines and that catalysed
hydroboration of these products gives multiply borated amines
proposed to result from competing enamine insertion into M–H
vs. M–B bonds. The first examples of metal-catalysed enamine
hydroboration reported herein afford boronate esters which may
subsequently be used as substrates to prepare novel function-
alized amines. This work is currently in progress.
R. T. B. thanks the Science and Technology Based programs
at Los Alamos and S. A. W. thanks the Natural Sciences and
Engineering Research Council of Canada.
11 (a) K. Burgess, W. A. van der Donk, S. A. Westcott, R. T. Baker, T. B.
Marder and J. C. Calabrese, J. Am. Chem. Soc., 1992, 114, 9350;
(b) S. A. Westcott, T. B. Marder and R. T. Baker, Organometallics,
1993, 12, 975; (c) J. M. Brown and G. C. Lloyd-Jones, J. Am. Chem.
Soc., 1994, 116, 866.
12 M. T. Atlay, L. R. Gahan, K. Kite, K. Moss and G. Read, J. Mol. Catal.,
1980, 7, 31.
13 H. Kono, K. Ito and Y. Nagai, Chem. Lett., 1975, 1095; D. Ma¨nnig and
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Chem., Int. Ed. Engl., 1995, 34, 115.
15 A small amount ( < 5%) of N-borylenamine is also observed in the
uncatalysed hydroborations due to HBcatA reaction with the N–H bond
of the enamine tautomer, PhNHCPhNCH2.
16 Uncatalysed hydroboration of enamines using alkylboranes can be
employed to prepare alkenes (after thermal elimination): B. Singaram,
C. T. Goralski and G. B. Fisher, J. Org. Chem., 1991, 56, 5691; G. B.
Fisher, C. T. Goralski, L. W. Nicholson and B. Singaram, Tetrahedron
Lett., 1993, 34, 7693.
Notes and references
† Dedicated to Professor Warren R. Roper on the occasion of his 60th
birthday.
‡ Reaction of 1 with B2catA2: to a solution of ketimine 1a (97 mg, 0.5 mmol)
dissolved in 0.5 ml of C6D6 was added B2catA2 (119 mg, 0.5 mmol) and
catalyst (2 mol%). The reaction was monitored by 1H and 11B NMR until 1a
was consumed (ca. 48 h). Similar reactions were conducted for 1b–e and
faster rates were observed for more electron-rich imines. The ratio of 2:3
was 4, 3.3, 2, 1.5, and 6 for 1a–e, respectively. For 1c, one equiv. of HBcatA
was added to the reaction mixture upon completion in order to cleanly
generate 4c from 2c.
Reaction of 1 with HBcatA: to a solution of ketimine 1a (40 mg, 0.2 mmol)
dissolved in 0.5 ml of [2H8]THF was added HBcatA (106 mg, 0.6 mmol) and
catalyst (2 mol%). The reaction was monitored by 1H and 11B NMR until the
intermediate N-borylenamine 2 was entirely consumed. The ratio of 3:4:5
was determined by 1H NMR before and after hydrolysis (see electronic
supplementary material for NMR data: http://www.rsc.org./suppdata/cc/
1998/2395). Product Ratios for 1a–e + HBcatA in THF after 4 days at 25 °C:
Communication 8/05792C
2396
Chem Commun., 1998