Mechanistic investigation of the selective reduction of Meldrum's acids to β-hydroxy acids using SmI2 and H2O

Article abstract of DOI:10.1039/c4cc03216k

The mechanism of a recently reported first mono-reduction of cyclic 1,3-diesters (Meldrum's acids) to β-hydroxy acids with SmI ₂-H₂O has been studied using a combination of reactivity, deuteration, kinetic isotope and radical clock e

Full text of DOI:10.1039/c4cc03216k

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Mechanistic investigation of the selective
reduction of Meldrum’s acids to b-hydroxy acids
using SmI2 and H2O†
Cite this: Chem. Commun., 2014,
50, 8391
Received 30th April 2014,
Accepted 5th June 2014
Michal Szostak,* Sarah E. Lyons, Malcolm Spain and David J. Procter*
DOI: 10.1039/c4cc03216k
www.rsc.org/chemcomm
The mechanism of a recently reported first mono-reduction of
cyclic 1,3-diesters (Meldrum’s acids) to b-hydroxy acids with
SmI2–H2O has been studied using a combination of reactivity,
deuteration, kinetic isotope and radical clock experiments. Most
crucially, the data indicate that the reaction proceeds via reversible
electron transfer and that water, as a ligand for SmI2, stabilizes the
radical anion intermediate rather than only promoting the first
electron transfer as originally proposed.
Reduction of carbonyl groups with low-valent metals to gen-
erate ketyl intermediates is a fundamental process in organic
synthesis.1 For more polar carboxylic acid derivatives, single
electron transfer from the metal centre to form acyl-type
radicals is more challenging due to lower electrophilicity of
the carbonyl group precursors, which prevents selective elec-
tron transfer under mild conditions.2 Moreover, the formed
acyl-type radicals often undergo undesired decarbonylation to
give carbon monoxide and alkyl radicals.3 Accordingly, success-
ful examples of generation of acyl-type radicals from polar
carbonyl groups remain rare.1–3
Fig. 1 (A) Previous studies: chemoselective electron transfer to Mel-
drum’s acids (reduction, cyclization and cyclization cascades). (B) This
work: mechanistic investigation and role of water.
groups of cyclic 1,3-diesters (Fig. 1)10 and lactones11 in that
Over the past decade, samarium(II) iodide (SmI2, Kagan’s the system shows full selectivity for the electron transfer to
reagent) has emerged as a valuable reagent for promoting cyclic esters over their acyclic analogues. The reduction of cyclic
10
electron transfer processes to carboxylic acid derivatives.4,5 In 1,3-diesters (Meldrum’s acids) with SmI2 is of particular
particular, the reagent formed by activation of SmI2 with Lewis interest for the synthesis of b-hydroxy acids – important building
basic ligands6 has enabled mild and modular synthesis of acyl- blocks for the synthesis of pharmaceuticals and polymers12
–
type radical intermediates from various carboxylic acid pre- directly from Meldrum’s acids.13 Furthermore, the easily
cursors.7,8 Perhaps most intriguing among these reagents are assembled a,b-unsaturated Meldrum’s acids13 undergo sequen-
SmI2–H2O complexes6b formed via the addition of water to tial reductions in the presence of SmI2–H2O,10a providing a
SmI2(THF)n due to their excellent chemoselectivity in diverse general route for the synthesis of b-hydroxy acids, while other
radical reactions.9
methods involve multiple steps.14 Finally, a large scale practical
Recently, our laboratory has demonstrated that SmI2–H2O reduction of Meldrum’s acids using SmI2–H2O has been devel-
exhibits remarkable selectivity in the reduction of carbonyl oped,10d,e and the potential of acyl-type radical intermediates in
cyclizations and reaction cascades has been demonstrated;10b,c
School of Chemistry, The University of Manchester, Oxford Road, Manchester,
however, at present the effect of the reaction components on the
generation of acyl-type radicals from Meldrum’s acids remains
unclear.
M13 9PL, UK. E-mail: michal.szostak@manchester.ac.uk,
david.j.procter@manchester.ac.uk; Fax: +44 (0)161 2754939;
Tel: +44 (0)161 2751425
Herein, we report the mechanistic investigation of the
SmI2–H2O-promoted first mono-reduction of Meldrum’s acids
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc03216k
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Table 1 Intermolecular competition experiments in the reduction of
Meldrum’s acids using SmI2–H2Oa
b
Entry
A
B
R1, R2
R3, R4
kA/kB
1
2
3
4
5
6
1a
1b
1a
1d
1e
1d
1b
1c
1c
1a
1c
1e
Ph, H
Bn, H
Ph, H
Ph, Me
i-Bu, Me
Ph, Me
Bn, H
1.66
2.46
5.21
420 : 1
420 : 1
3.74
Fig. 2 (a) Plot of conversion vs. concentration of H2O for reduction of 1c.
(b) Plot of conversion vs. concentration of SmI2 for reduction of 1d.
i-Bu, H
i-Bu, H
Ph, H
i-Bu, H
i-Bu, Me
in the reduction of lactones and acyclic esters.15a,b We hypothesize
that the steric acceleration in the present case results from a
7c,d
8c,d
9d
1f
1f
1h
1h
1f
1e
1d
1e
1d
1h
1g
QCHi-Pr
QCHi-Pr
–(CH2)2–
–(CH2)2–
QCHi-Pr
QCHi-Pr
i-Bu, Me
Ph, Me
i-Bu, Me
Ph, Me
–(CH2)2–
QCHPh
420 : 1
420 : 1 torsional strain in the radical anion intermediate in a half-chair
420 : 1
5.13
420 : 1
conformation.10a,b
10d
11c,d
12c,d
Evidence for the reaction pathway was further gained by
examining the reactivity of substrates possessing two reactive
sites (entries 7–12). These results indicate that a,b-unsaturated
Meldrum’s acids undergo chemoselective reduction in prefer-
ence to their fully saturated counterparts (entries 7 and 8).
Moreover, a cyclopropyl-clock containing substrate results in a
faster reduction than for a,a-disubstituted Meldrum’s acids
(entries 9 and 10); however, its reduction is slower than that
1f
1.37
a
Conditions: Meldrum’s acid (1 equiv.), SmI2 (2 equiv., THF), H2O
(400 equiv.), 23 1C. Reaction time 30–60 s. Determined by 1H NMR.
b
c
SmI2 (1 equiv.), H2O (200 equiv.). In all entries 495% yield based on
d
reacted starting material. Selective exo-cyclic reduction of olefin/cyclo-
propane to give the corresponding substituted Meldrum’s acids. See ESI.
to b-hydroxy acids. The reaction proceeds via acyl-type radical of an a,b-unsaturated ester (entry 11). Finally, electronically-
intermediates generated by a direct electron transfer from differentiated a,b-unsaturated substrates result in a near
Sm(II) to the ester carbonyl. The study represents one of the statistical rate of reduction (entry 12). These results outline
first mechanistic analyses of electron transfer processes to the order of reactivity of Meldrum’s acids with SmI2:
carbonyl groups mediated by SmI2.15 Importantly, this investi- a,b-unsaturated
c
cyclopropyl
4
a,a-disubstituted
c
gation outlines the interplay between SmI2 and H2O ligand,16 a-monosubstituted.18 Importantly, the data presented in
establishes the reversibility of the initial electron transfer and Table 1 indicate high levels of chemoselectivity in the reduction
provides insights for the rational development of radical reac- of Meldrum’s acids with SmI2–H2O.5f
tions based on the versatile Meldrum’s acid template using
Sm(II) complexes.
To investigate the role of water as an activating ligand for
Sm(II), a series of rate studies were performed (Fig. 2a and
Initial studies suggested that selectivity in the mono- ESI†). Isobutyl-substituted ester was selected as a model sub-
reduction of Meldrum’s acids resulted from the rate of the strate. The study was performed by monitoring the reduction of
initial electron transfer to the carbonyl group and anomeric 1c with increasing concentrations of water and quenching the
stabilization of the radical anion intermediate.10a,b Moreover, reaction at low conversions. Remarkably, a non-linear depen-
water as the ligand to Sm(II) was critical for the observed dence on water concentration was found in the reduction of 1c
reactivity. However, after continuous probing of the reaction (Fig. 2a). In agreement with the previous results, no reaction
pathway, several observations suggested that an alternative was observed without the water additive and at low concen-
mechanism might be operative.
tration of water,10a,b (0–50 equiv.; see, ESI†). Next, at higher
To elucidate the role of electronic and steric stabilization in concentrations of water (100–400 equiv.) the rate was found to
the SmI2-mediated reduction of Meldrum’s acids, a series of increase linearly with a slope. However, at high concentrations
reactivity studies were performed (Table 1).17 Because of the of water (4400 equiv.) the rate decreased dramatically, which is
heterogenicity of the reaction, kinetic studies proved not to be a consistent with substrate dissociation from the inner coordina-
viable tool in the present reaction. Remarkably, in the series of tion sphere of Sm(II).15 These results are in contrast to the
selected substrates (Table 1, entries 1–6) full selectivity for the thermodynamic redox potentials of SmI2–H2O complexes15d
reduction of alpha-disubstituted esters over alpha-monosubstituted and other studies.11b Importantly, the rate of reduction of
esters was observed (Table 1, entries 4 and 5). Moreover, appreci- acyl-type radicals can be varied by simply changing the concen-
able levels of selectivity were obtained depending on electronic tration of the water additive.19
properties of the a-carbon substituent at the ester group under-
We likewise investigated the role of SmI2 in the reduction of
going the reduction (Table 1, entries 1–3 and 6) consistent with Meldrum’s acids (Fig. 2b and ESI†). The study was performed
electronic stabilization of ketyl-type radicals. The steric acceleration by monitoring the equivalents of SmI2 required for the
of the reduction is unexpected and contrasts with the previously reduction of 1d with a set concentration of water and quench-
observed steric inhibition of coordination of polar groups to Sm(II) ing the reaction after disappearance of the active Sm(II)
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Table 2 Radical clock fragmentation studies in the reduction of Mel-
a
drum’s acids using SmI2
SmI2
ROH
(equiv.) Time
Conv.b 2h : 2ib
Entry (equiv.) ROH
(%)
(%)
1
2
10
3
H2O
H2O
MeOH
—
200
1000
200
—
o1 min
87
495 : 5
o5 : 495
495 : 5
495 : 5
2c
3d
4e
2 h
1 h
3 h
495
495
50
Scheme 1 Proposed mechanism of the reduction of Meldrum’s acids.
3
a
Conditions: Meldrum’s acid (1 equiv.), SmI2 (in THF), ROH, 23 1C.
Determined by 1H NMR. Combined yield of 2h and 2i. Entries 1–3,
resulted in a full reduction to the b-hydroxy acid. The reduction
with SmI2–H2O (8 equiv., 15 min) gave approx. 1 : 1 ratio of 2h to
2i. The reduction using SmI2–MeOH and SmI2–THF resulted in
alcoholysis and slow, non-selective reaction. Overall, these
findings strongly suggest that the reduction of Meldrum’s acids
b
c
d
485% yield based on reacted starting material. Ref. 10a. Fragmen-
tation product consists of 2h and its methanolysis product (15 : 85).
e
Entry 4, 23% yield. See ESI for full experimental details.
complex. As indicated in Fig. 2b, the reaction of 1d is linear in with SmI2–H2O occurs via fast, reversible electron transfer and
SmI2 and requires more than six equivalents of the reductant. that water activates the reagent towards the electron transfer.
This is consistent with previous mechanistic studies on the
Additional experiments were performed to gain insight into
reduction of carbonyl groups with SmI215 and indicates that the the electron transfer steps (see ESI† and Table 3). (1) The
collapse of acetonide occurs prior to the final electron transfer reduction of a series of a-mono and a,a-disubstituted substrates
from Sm(II).
with SmI2–D2O gives the b-hydroxy acid products with 498% D2
To gain independent evidence on the role of electron and D3 incorporation, suggesting that anions are protonated in a
transfer steps, we carried out experiments employing cyclopro- series of electron transfer steps (see ESI†). Control reactions
pyl clocks (Table 2 and ESI†).20 The reaction of 1h (2 equiv. of demonstrate that a-proton exchange is faster than the reduction
SmI2) resulted in rapid cyclopropyl ring opening to give acyclic (see ESI†). (2) The secondary kinetic isotope effect in the reduction
ester 2h. Cyclopropyl carbinol was not detected in the reaction. of 1d of 1.5 (intramolecular competition) suggests that proton
The reaction with excess of SmI2–H2O (10 equiv., rt, 2 h) transfer to carbon is not involved in the rate determining step of
the reaction (see ESI†).21 (3) The reduction of a,b-unsaturated
Meldrum’s acids 1f and 1g (SmI2, 2 equiv.) proceeds with full
selectivity for the 1,4-reduction to give saturated Meldrum’s acid
derivatives (see ESI†). (4) Evaluation of the reduction of the
Table 3 Evaluation of chemoselectivity in the reduction of Meldrum’s
acids using SmI2–ROH/L.B. systemsa
benchmark substrate using various Sm(II)–ROH systems indicates
that other SmI2 reagents can be used to promote selective mono-
reduction (Table 3). Importantly, under the optimized reaction
conditions over-reduction to 1,3-diol is not observed. Note, how-
ever, that the reactivity trend is divergent from the ligand effect on
ROH/L.B.
(equiv.)
Yieldb Selectivity
Time (%)
the reduction of other carbonyl groups using Sm(II),15f which most
likely results from a combination of lower kinetic reactivity of
these substrates (entries 1–4), instability towards the reaction
conditions (entries 5 and 6), and differential coordination of the
sterically-encumbered reductants to the Meldrum’s acid carbonyl
groups (entries 7–12). Overall, these results demonstrate that
Sm(II) reagents based on chelating ligands6 and multicomponent
systems7 are new chemoselective reductants available for the
reduction of cyclic 1,3-diesters.
Scheme 1 shows a revised mechanism that is consistent with
the kinetic and reactivity studies presented herein. The key
features involve: (1) reversible initial electron transfer step; (2)
non-linear rate dependence on water concentration; (3) rate
Entry ROH/L.B.
2d : 2kb (%)
1
2
3
4
MeOH
ED
DCH
EG
4/1 v/v
36
36
2 h
2 h
2 h
2 h
o5
o5
o5
84
—
—
—
495 : 5
36
5
6
7
n-BuNH2/H2O
Pyrrolidine/H2O
Et3N/H2O
12/18
12/18
12/18
12/18
12/18
12/18
5 min o5
5 min o5
5 min 92
5 min 84
—
—
495 : 5
495 : 5
—
495 : 5
495 : 5
495 : 5
8
9
10
11
12
Et3N/EG
Et3N/MeOH
TMEDA/H2O
2 h
o5
5 min 46
5 min 80
5 min 48
N-Me-morpholine/H2O 12/18
DIPA/H2O 12/18
a
Conditions: Meldrum’s acid (1 equiv.), SmI2 (4–6 equiv., THF), 23 1C.
b
In all entries, preformed solution of SmI2–ROH/L.B. was used. Deter- determining second electron transfer step that is inhibited by
mined by 1H NMR. In all entries, yield based on reacted starting
large concentrations of water.
material. ED
cyclohexyldiamine; EG
ethylenediamine.
= Ethylenediamine; DCH =
trans-N,N0-dimethyl-1,2-
In conclusion, we have elucidated the mechanism of the
selective mono-reduction of Meldrum’s acids to b-hydroxy acids
= ethylene glycol; TMEDA = tetramethyl-
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10 (a) G. Guazzelli, S. De Grazia, K. D. Collins, H. Matsubara, M. Spain
and D. J. Procter, J. Am. Chem. Soc., 2009, 131, 7214; (b) K. D. Collins,
J. M. Oliveira, G. Guazzelli, B. Sautier, S. De Grazia, H. Matsubara,
M. Helliwell and D. J. Procter, Chem. – Eur. J., 2010, 16, 10240;
(c) B. Sautier, S. E. Lyons, M. R. Webb and D. J. Procter, Org. Lett.,
2012, 14, 146; (d) M. Szostak, M. Spain and D. J. Procter, Nat. Protoc.,
2012, 7, 970; Detailed study on the preparation of SmI2:
(e) M. Szostak, M. Spain and D. J. Procter, J. Org. Chem., 2012,
77, 3049; ( f ) M. Szostak, B. Sautier, M. Spain, M. Behlendorf and
D. J. Procter, Angew. Chem., Int. Ed., 2013, 52, 12559.
using the SmI2–H2O system. We hope that further research
aimed at understanding processes involving activation of SmI2
by Lewis basic ligands will enable discovery of new radical
reactions.
We are grateful to the EPRSC and GSK for financial support.
Notes and references
1 Reviews on metal-mediated radical reactions: (a) B. M. Trost and 11 (a) L. A. Duffy, H. Matsubara and D. J. Procter, J. Am. Chem. Soc.,
I. Fleming, Comprehensive Organic Synthesis, Pergamon Press, 1991;
2008, 130, 1136; (b) D. Parmar, L. A. Duffy, D. V. Sadasivam,
H. Matsubara, P. A. Bradley, R. A. Flowers, II and D. J. Procter,
J. Am. Chem. Soc., 2009, 131, 15467; (c) D. Parmar, K. Price, M. Spain,
H. Matsubara, P. A. Bradley and D. J. Procter, J. Am. Chem. Soc., 2011,
133, 2418; (d) D. Parmar, H. Matsubara, K. Price, M. Spain and
D. J. Procter, J. Am. Chem. Soc., 2012, 134, 12751; (e) M. Szostak,
M. Spain, K. A. Choquette, R. A. Flowers, II and D. J. Procter, J. Am.
Chem. Soc., 2013, 135, 15702; Application to TmI2–H2O:
( f ) M. Szostak, M. Spain and D. J. Procter, Angew. Chem., Int. Ed.,
2013, 52, 7237. Application to Birch reductions: (g) M. Szostak,
M. Spain and D. J. Procter, J. Org. Chem., 2014, 79, 2522.
¨
(b) A. Gansauer and H. Bluhm, Chem. Rev., 2000, 100, 2771;
(c) M. Szostak and D. J. Procter, Angew. Chem., Int. Ed., 2012,
51, 9238; (d) J. Streuff, Synthesis, 2013, 45, 281.
2 For reviews see: (a) P. Renaud and M. Sibi, Radicals in Organic
Synthesis, Wiley-VCH, 2001; (b) C. Chatgilialoglu and A. Studer,
Encyclopedia of Radicals in Chemistry, Biology and Materials, Wiley-
Blackwell, 2012; (c) T. Wirth, Angew. Chem., Int. Ed. Engl., 1996,
35, 61; (d) J. Murphy, J. Org. Chem., 2014, 79, 3731.
3 For a comprehensive review, see: (a) C. Chatgilialoglu, D. Crich,
M. Komatsu and I. Ryu, Chem. Rev., 1999, 99, 1991; For an elegant
solution using SmI2, see: (b) C. M. Jensen, K. B. Lindsay, 12 Representative examples: (a) B. Hu, M. Prashad, D. Har, K. Prasad,
ˇ
R. H. Taaning, J. Karaffa, A. M. Hansen and T. Skrydstrup, J. Am.
Chem. Soc., 2005, 127, 6544.
4 D. J. Procter, R. A. Flowers, II and T. Skrydstrup, Organic Synthesis using
Samarium Diiodide: A Practical Guide, RSC Publishing, Cambridge, 2009.
5 Recent reviews on SmI2: (a) H. B. Kagan, Tetrahedron, 2003,
O. Repic and T. J. Blacklock, Org. Process Res. Dev., 2007, 11, 90;
(b) H. S. Lee and D. H. Kim, Bioorg. Med. Chem., 2003, 11, 4685;
(c) P. M. Chaudhari, P. V. Kawade and S. M. Funne, Int. J. Pharm.
Technol., 2011, 3, 774; (d) D. Zhang, M. A. Hillmyer and
W. B. Tolman, Macromolecules, 2004, 37, 8198.
59, 10351; (b) D. J. Edmonds, D. Johnston and D. J. Procter, Chem. 13 Comprehensive reviews on Meldrum’s acids: (a) H. McNab, Chem.
Rev., 2004, 104, 3371; (c) K. C. Nicolaou, S. P. Ellery and J. S. Chen,
Angew. Chem., Int. Ed., 2009, 48, 7140; (d) C. Beemelmanns and
H. U. Reissig, Chem. Soc. Rev., 2011, 40, 2199; (e) M. Szostak and 14 M. O. Polla, L. Tottie, C. Norden, M. Linschoten, D. Mu¨sila,
Soc. Rev., 1978, 7, 345; (b) B. C. Chen, Heterocycles, 1991, 32, 529;
(c) A. M. Dumas and E. Fillion, Acc. Chem. Res., 2010, 43, 440.
´
D. J. Procter, Angew. Chem., Int. Ed., 2011, 50, 7737; ( f ) M. Szostak,
M. Spain and D. J. Procter, Chem. Soc. Rev., 2013, 42, 9155;
(g) M. Szostak, N. J. Fazakerley, D. Parmar and D. J. Procter, Chem.
Rev., 2014, 114, DOI: 10.1021/cr400685r.
S. Trumpp-Kallmeyer, I. R. Aukrust, R. Ringom, K. H. Holm,
S. M. Neset, M. Sandberg, J. Thurmond, P. Yu, G. Hategan and
H. Anderson, Bioorg. Med. Chem., 2004, 12, 1151.
15 Relevant studies on mechanisms of SmI2-mediated reactions:
(a) M. Szostak, M. Spain and D. J. Procter, Chem. – Eur. J., 2014,
20, 4222; (b) M. Szostak, M. Spain and D. J. Procter, J. Am. Chem.
Soc., 2014, 136, DOI: 10.1021/ja503494b; (c) T. Ankner and
G. Hilmersson, Tetrahedron, 2009, 65, 10856; (d) P. R. Chopade,
E. Prasad and R. A. Flowers, II, J. Am. Chem. Soc., 2004, 126, 44;
(e) E. Prasad and R. A. Flowers, II, J. Am. Chem. Soc., 2005,
127, 18093; ( f ) D. V. Sadasivam, J. A. Teprovich, Jr., D. J. Procter
and R. A. Flowers, II, Org. Lett., 2010, 12, 4140.
6 For reviews on the influence of additives on properties of SmI2, see:
´
(a) A. Dahlen and G. Hilmersson, Eur. J. Inorg. Chem., 2004, 3393;
(b) M. Szostak, M. Spain, D. Parmar and D. J. Procter, Chem.
Commun., 2012, 48, 330.
7 For early studies, see: (a) Y. Kamochi and T. Kudo, Chem. Lett., 1993,
1495; (b) Y. Kamochi and T. Kudo, Tetrahedron, 1992, 48, 4301;
Recent examples: (c) M. Szostak, M. Spain and D. J. Procter, Chem.
Commun., 2011, 47, 10254; (d) M. Szostak, M. Spain and D. J. Procter,
Org. Lett., 2012, 14, 840; (e) M. Szostak, K. D. Collins, 16 (a) A. Yacovan, I. Bilkis and S. Hoz, J. Am. Chem. Soc., 1996, 118, 261;
N. J. Fazakerley, M. Spain and D. J. Procter, Org. Biomol. Chem.,
2012, 10, 5820; ( f ) M. Szostak, M. Spain, A. J. Eberhart and
D. J. Procter, J. Am. Chem. Soc., 2014, 136, 2268; (g) M. Szostak,
B. Sautier, M. Spain and D. J. Procter, Org. Lett., 2014, 16, 1092.
8 Representative examples of Sm(II)-Lewis base systems in other
(b) A. Tarnopolsky and S. Hoz, J. Am. Chem. Soc., 2007, 129, 3402;
(c) M. Amiel-Levy and S. Hoz, J. Am. Chem. Soc., 2009, 131, 8280;
(d) S. K. Upadhyay and S. Hoz, J. Org. Chem., 2011, 76, 1355.
17 R. H. Taaning, K. B. Lindsay, B. Schiøtt, K. Daasbjerg and
T. Skrydstrup, J. Am. Chem. Soc., 2009, 131, 10253.
´
´
transformations: (a) A. Dahlen and G. Hilmersson, Tetrahedron Lett., 18 Relative reactivity of Meldrum’s acids with SmI2–H2O: Meldrum’s
2002, 43, 7197; (b) A. Dahlen and G. Hilmersson, J. Am. Chem. Soc.,
acids c barbituric acids c lactones. See, ref. 10f.
2005, 127, 8340; (c) C. Beemelmanns and H. U. Reissig, Angew. 19 The onset of reactivity and maximum rate of the reduction of
Chem., Int. Ed., 2010, 49, 8021; (d) Z. Li, M. Nakashige and
W. J. Chain, J. Am. Chem. Soc., 2011, 133, 6553.
9 Representative examples of SmI2–H2O systems: (a) E. Hasegawa and
D. P. Curran, J. Org. Chem., 1993, 58, 5008; (b) G. Masson,
Meldrum’s acids is shifted towards higher concentrations of water
than the reduction of lactones using SmI2–H2O, despite the rate of
lactone reduction being slower than the rate of Meldrum’s acid
reduction.18 See, also: H. Farran and S. Hoz, Org. Lett., 2008, 10, 4875.
´
P. Cividino, S. Py and Y. Vallee, Angew. Chem., Int. Ed., 2003, 20 M. Newcomb, Tetrahedron, 1993, 49, 1151.
42, 2265; (c) P. Gilles and S. Py, Org. Lett., 2012, 14, 1042. 21 E. M. Simmons and J. F. Hartwig, Angew. Chem., Int. Ed., 2012, 51, 3066.
8394 | Chem. Commun., 2014, 50, 8391--8394
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