Catalytic anomeric aminoalkynylation of unprotected aldoses

Article abstract of DOI:10.1021/ol401810b

A copper(I)-catalyzed anomeric aminoalkynylation reaction of unprotected aldoses was realized. Use of an electron-deficient phosphine ligand, boric acid to stabilize the iminium intermediate, and a protic additive (IPA) to presumably enhance reversible carbohydrate-boron complexation were all essential for efficient conversion. The reaction proceeded well even with a natural disaccharide substrate, suggesting that the developed catalytic reaction could be useful for the synthesis of glycoconjugates with minimum use of protecting groups.

Full text of DOI:10.1021/ol401810b

ORGANIC
LETTERS
2013
Vol. 15, No. 16
4130–4133
Catalytic Anomeric Aminoalkynylation
of Unprotected Aldoses
Yasuaki Kimura, Soichi Ito, Yohei Shimizu, and Motomu Kanai*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1, Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan, and ERATO, Japan Scienceand TechnologyAgency,
Kanai Life Science Catalysis Project, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
kanai@mol.f.u-tokyo.ac.jp
Received June 27, 2013
ABSTRACT
A copper(I)-catalyzed anomeric aminoalkynylation reaction of unprotected aldoses was realized. Use of an electron-deficient phosphine ligand,
boric acid to stabilize the iminium intermediate, and a protic additive (IPA) to presumably enhance reversible carbohydrateÀboron complexation
were all essential for efficient conversion. The reaction proceeded well even with a natural disaccharide substrate, suggesting that the developed
catalytic reaction could be useful for the synthesis of glycoconjugates with minimum use of protecting groups.
Oligosaccharides and glycoconjugates have significant
roles in a diverse set of biological processes, such as viral
infections, cell growth, and immunoresponses.1 Synthesis
of these highly polar, multifunctional molecules relies
predominantly on the extensive use of protecting groups
(PGs)2 for chemo- and position-selective transformations.3,4
The use of PGs, however, generally impairs synthetic effi-
ciency5,6 in terms of atom7- and step8-economy. These
drawbacks of PGs are prevalent especially in the synthesis
of carbohydrate derivatives. Although some studies have
reported that a minimum use of PGs streamlines the
synthesis of carbohydrate derivatives,9 the number of such
pioneering works is limited. These examples demonstrate
that CÀC bond-forming reactions at the anomeric carbon
of unprotected carbohydrates are key components of the
(1) (a) Varki, A.; Cummings, R. D.; Esko, J.; Freeze, H. H.; Stanley,
P.; Bertozzi, C. R.; Hart, G. W.; Etzler, M. E. Essentials of Glycobiology;
Cold Spring Harbor Laboratory Press, 2009. (b) Ernst, B.; Hart, G. W.; Sina,
P. Carbohydrates in Chemistry and Biology; Wiley-VCH Verlag GmbH:
Weinheim, Germany, 2000.
(2) Wuts, P. G. M.; Greene, T. W. Greene’s Protective Groups in
Organic Synthesis; John Wiley & Sons: Hoboken, NJ, 2007.
(3) Representative reviews on chemoselectivity: (a) Trost, B. M.
Science 1983, 219, 245. (b) Shenvi, R. A.; O’Malley, D. P.; Baran, P. S.
Acc. Chem. Res. 2009, 42, 530. (c) Afagh, N. A.; Yudin, A. K. Angew.
Chem., Int. Ed. 2010, 49, 262.
(4) For recent reviews and reports on position-selective transforma-
tions of polyols in carbohydrate derivatives, see: (a) Lee, D.; Taylor,
M. S. Synthesis 2012, 44, 3421. (b) Oshima, K.; Aoyama, Y. J. Am.
Chem. Soc. 1999, 121, 2315. (c) Griswold, K. S.; Miller, S. J. Tetrahedron
2003, 59, 8869. (d) Kawabata, T.; Muramatsu, W.; Nishio, T.; Shibata,
T.; Schedel, H. J. Am. Chem. Soc. 2007, 129, 12890. (e) Fiori, K. W.;
Puchlopek, A. L. A.; Miller, S. J. Nat. Chem 2009, 1, 630. (f) Lee, D.;
Williamson, C. L.; Chan, L.; Taylor, M. S. J. Am. Chem. Soc. 2012, 134,
8260. (g) Muramatsu, W. J. Org. Chem. 2012, 77, 8083.
(7) Trost, B. M. Science 1991, 254, 1471.
(8) (a) Wender, P. A.; Verma, V. A.; Paxton, T. J.; Pillow, T. H. Acc.
Chem. Res. 2008, 41, 40. (b) Wender, P. A.; Croatt, M. P.; Witulski, B.
Tetrahedron 2006, 62, 7505.
(9) (a) Gordon, D. M.; Whitesides, G. M. J. Org. Chem. 1993, 58,
7937. (b) Hong, Z.; Liu, L.; Hsu, C.-C.; Wong, C.-H. Angew. Chem., Int.
Ed. 2006, 45, 7417. (c) Hong, Z.; Liu, L.; Sugiyama, M.; Fu, Y.; Wong,
C.-H. J. Am. Chem. Soc. 2009, 131, 8352.
(5) For reviews on PG-free synthesis of natural products, see: (a)
Hoffmann, R. Synthesis 2006, 3531. (b) Baran, P. S.; Maimone, T. J.;
Richter, J. M. Nature 2007, 446, 404. (c) Young, I. S.; Baran, P. S. Nat.
Chem. 2009, 1, 193.
(10) (a) Kiliani, H. Ber. Dtsch. Chem. Ges 1886, 19, 767. (b) Lundt, I.;
Madsen, R. Synthesis 1995, 787. (c) Hotchkiss, D.; Soengas, R.; Simone,
M. I.; van Ameijde, J.; Hunter, S.; Cowley, A. R.; Fleet, G. W. J.
Tetrahedron Lett. 2004, 45, 9461. (d) Soengas, R.; Izumori, K.; Simone,
M. I.; Watkin, D. J.; Skytte, U. P.; Soetaert, W.; Fleet, G. W. J.
Tetrahedron Lett. 2005, 46, 5755.
(6) Recent representative reports on PG-free synthesis of complex
€
natural products: (a) Hickmann, V.; Alcarazo, M.; Furstner, A. J. Am.
Chem. Soc. 2010, 132, 11042. (b) Gerfaud, T.; Xie, C.; Neuville, L.; Zhu,
J. Angew. Chem., Int. Ed. 2011, 50, 3954. (c) Liu, G.; Romo, D. Angew.
Chem., Int. Ed. 2011, 50, 7537. (d) Xu, J.; Caro-Diaz, E. J. E.; Trzoss, L.;
Theodorakis, E. A. J. Am. Chem. Soc. 2012, 134, 5072. (e) Waldeck,
A. R.; Krische, M. J. Angew. Chem., Int. Ed. 2013, 52, 4470.
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€
69, 1963. (b) Koll, P.; Stenns, C.; Seelhorst, W.; Brandenburg, H. Liebigs
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Ann. Chem. 1991, 201. (c) Dromowicz, M.; Koll, P. Carbohydr. Res.
ꢀ
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1998, 308, 169. (d) Vojtech, M.; Petrusova, M.; Pribulova, B.; Petrus, L.
Tetrahedron Lett. 2008, 49, 3112.
r
10.1021/ol401810b
Published on Web 07/31/2013
2013 American Chemical Society

methodology. Representative nucleophiles applied in these
reactions are the cyanide anion10 (Kiliani reaction),
nitromethane11 (FischerÀSowden reaction), phosphorus
ylides,12 1,3-dicarbonyl compounds,13 allyl metal species,9a,14
vinyl boronic acid esters,9b,c and aryl compounds.14h,15
Precedents that allow for the convergent incorporation of
molecular skeletal fragments with multiple functional
groups are scarce, however, despite their high synthetic
utility. Furthermore, the available reports include only a
limited number of catalytic reactions.13j,l,m,14g,14h,15
higher-carbon sugars.19 In addition, the reaction would be
useful for the concise synthesis of glycoconjugates of func-
tional organic molecules, such as biotin derivatives and
fluorescent probes. The orthogonal reactivity of soft
nucleophile20 and hard hydroxy groups of the substrate
would be an essential factor to realize the target CÀC bond
formation. We herein report a copper-catalyzed anomeric
aminoalkynylation reaction of unprotected aldoses.
To broaden the scope of carbon nucleophiles that could be
catalytically coupled with unprotected aldoses, we became
interested in alkynes. Specifically, aminoalkynylation16 of
unprotected aldoses17 affords nitrogen-containing polyol
structures with elongated carbon chains18 that could be
potential synthetic intermediates for nitrogen-containing
Table 1. Optimization of Catalytic Aminoalkynylation of
D-Arabinose
(12) (a) Bestmann, H. J.; Angerer, J. Tetrahedron Lett. 1969, 10, 3665.
(b) Henk, T.; Giannis, A.; Sandhoff, K. Liebigs Ann. Chem. 1992, 167. (c)
Railton, C. J.; Clive, D. L. J. Carbohydr. Res. 1996, 281, 69. (d) Le
Mignot, V.; Lievre, C.; Frechou, C.; Demailly, G. Tetrahedron Lett.
1998, 39, 983. (e) Jørgensen, M.; Iversen, E. H.; Madsen, R. J. Org.
boron
entry
reagent
ligand
additive
yield
0%
ꢂ
ꢁ
1a,b
2a,b
3
none
none
none
none
none
none
PPh3
none
none
none
none
none
none
none
none
none
none
IPA
BF3 OEt2
18%
ꢂ
ꢁ
Chem. 2001, 66, 4625. (f) Ranoux, A.; Lemiegre, L.; Benoit, M.; Guegan,
J.-P.; Benvegnu, T. Eur. J. Org. Chem. 2010, 1314. (g) van Kalkeren,
H. A.; van Rootselaar, S.; Haasjes, F. S.; Rutjes, F. P. J. T.; van Delft,
F. L. Carbohydr. Res. 2012, 362, 30.
3
PhB(OH)2
B(OH)3
B(OEt)3
B(OH)3
B(OH)3
B(OH)3
B(OH)3
B(OH)3
B(OH)3
B(OH)3
B(OH)3
30%c
51%
4
5
51%
(13) (a) Cornforth, J. W.; Firth, M. E.; Gottschalk, A. Biochem. J. 1958,
68, 57. (b) Ghalambor, M. A.; Heath, E. C. Biochem. Biophys. Res.
Commun. 1963, 11, 288. (c) Gonzalez, M. A.; Jimenez Requejo, J. L.;
Palacios Albarran, J. C.; Gabis Perez, J. A. Carbohydr. Res. 1986, 158, 53.
(d) Shirai, R.; Ogura, H. Tetrahedron Lett. 1989, 30, 2263. (e) Wulff, G.;
Clarkson, G. Carbohydr. Res. 1994, 257, 81. (f) Rodrigues, F.; Canac, Y.;
Lubineau, A. Chem. Commun. 2000, 2049. (g) Riemann, I.; Fessner, W.-D.;
Papadopoulos, M. A.; Knorst, M. Aust. J. Chem. 2002, 55, 147. (h)
6
50%c
47%c,d
trace
65%c
73%c
62%
7
xantphose
8
dppef
9
P(3,5-(CF3)2-C6H3)3
P(C6F5)3
10
11
12
13
none
P(3,5-(CF3)2-C6H3)3
P(C6F5)3
IPA
71%c
84%
ꢁ
Cavezza, A.; Boulle, C.; Gueguiniat, A.; Pichaud, P.; Trouille, S.; Ricard,
L.; Dalko-Csiba, M. Bioorg. Med. Chem. Lett. 2009, 19, 845. (i) Winzar, R.;
Philips, J.; Kiefel, M. Synlett 2010, 583. (j) Feng, W.; Fang, Z.; Yang, J.;
Zheng, B.; Jiang, Y. Carbohydr. Res. 2011, 346, 352. (k) Wang, J.; Li, Q.;
Ge, Z.; Li, R. Tetrahedron 2012, 68, 1315. (l) Voigt, B.; Scheffler, U.;
Mahrwald, R. Chem. Commun. 2012, 48, 5304. (m) Voigt, B.; Matviitsuk,
A.; Mahrwald, R. Tetrahedron 2013, 69, 4302.
IPA
a 30 mol % of CuBr and 3 equiv of diallylamine were used. b Reaction
time was 12 h. c Determined by 1H NMR d dr: 1.8/1 e xantphos: 4,5-
Bis(diphenylphosphino)-9,9-dimethyl-xanthene f dppe: 1,2-Bis(diphenyl-
phosphino)ethane.
(14) (a) Schmid, W.; Whitesides, G. M. J. Am. Chem. Soc. 1991,
113, 6674. (b) Chan, T.-H.; Li, C.-J. J. Chem. Soc., Chem. Commun. 1992,
747. (c) Kim, E.; Gordon, D. M.; Schmid, W.; Whitesides, G. M. J. Org.
Chem. 1993, 58, 5500. (d) Prenner, R. H.; Binder, W. H.; Schmid, W.
Liebigs Ann. Chem. 1994, 73. (e) Toshima, K.; Ishizuka, T.; Matsuo, G.;
Nakata, M. Tetrahedron Lett. 1994, 35, 5673. (f) Chan, T.-H.; Lee, M.-
C. J. Org. Chem. 1995, 60, 4228. (g) Kobayashi, S.; Wakabayashi, T.;
Oyamada, H. Chem. Lett. 1997, 26, 831. (h) Toshima, K.; Matsuo, G.;
Ishizuka, T.; Ushiki, Y.; Nakata, M.; Matsumura, S. J. Org. Chem.
1998, 63, 2307. (i) Warwel, M.; Fessner, W.-D. Synlett 2000, 865. (j)
Palmelund, A.; Madsen, R. J. Org. Chem. 2005, 70, 8248. (k) Hansen,
F. G.; Bundgaard, E.; Madsen, R. J. Org. Chem. 2005, 70, 10139. (l)
We began our investigations using D-arabinose (1a),
ethynylbenzene (2a), and several amines as substrates
and Cu(I) salts as a catalyst. Initially, we tested CuBr
and diallylamine by following Knochel’s precedent,21 but
obtained no desired product (Table 1, entry 1). We hy-
pothesized that the low reactivity of arabinose was due to
its dominant hemiacetal form rather than a reactive alde-
hyde form.22 We therefore used Lewis acid additives,
expecting that they would promote the formation of the
aldehyde form from the hemiacetal form of arabinose.
Although the reactions with most Lewis acids were
€
Saloranta, T.; Muller, C.; Vogt, D.; Leino, R. Chem.;Eur. J. 2008, 14,
€
10539. (m) Schmolzer, C.; Fischer, M.; Schmid, W. Eur. J. Org. Chem.
2010, 4886. (n) Behr, J.-B.; Hottin, A.; Ndoye, A. Org. Lett. 2012, 14,
1536.
(15) (a) Toshima, K.; Matsuo, G.; Ishizuka, T.; Nakata, M.;
Kinoshita, M. J. Chem. Soc., Chem. Commun. 1992, 1641. (b) Toshima,
K.; Matsuo, G.; Nakata, M. J. Chem. Soc., Chem. Commun. 1994, 997.
(c) Matsuo, G.; Miki, Y.; Nakata, M.; Matsumura, S.; Toshima, K.
J. Org. Chem. 1999, 64, 7101.
(19) Representative reviews on the synthesis of higher-carbon sugars:
(a) Danishefsky, S. J.; DeNinno, M. P. Angew. Chem., Int. Ed. Engl.
1987, 26, 15. (b) Casiraghi, G.; Zanardi, F.; Rassu, G.; Spanu, P. Chem.
Rev. 1995, 95, 1677. (c) Kiefel, M. J.; von Itzstein, M. Chem. Rev. 2002,
102, 471. (d) Li, L. S.; Wu, Y. L. Curr. Org. Chem. 2003, 7, 447.
(20) Previously reported alkynylation reactions of aldehydes and
imines are mainly catalyzed by soft metal complexes such as Zn, Cu,
Ru, etc. For representative reviews, see: (a) Zani, L.; Bolm, C. Chem.
Commun. 2006, 4263. (b) Trost, B. M.; Weiss, A. H. Adv. Synth. Catal.
2009, 351, 963. (c) Li, C.-J. Acc. Chem. Res. 2010, 43, 581.
(21) Gommermann, N.; Koradin, C.; Polborn, K.; Knochel, P.
Angew. Chem., Int. Ed. 2003, 42, 5763.
(16) (a) Wei, C. M.; Li, Z. G.; Li, C. J. Synlett 2004, 1472. (b)
ꢁ
Kouznetsov, V. V.; Vargas Mendez, L. Y. Synthesis 2008, 491. (c)
Peshkov, V. A.; Pereshivko, O. P.; Van der Eycken, E. V. Chem. Soc.
Rev. 2012, 41, 3790.
(17) A stoichiometric gold-mediated aminoalkynylation reaction
of special oligosaccharides possessing an unmasked formyl group
(D-raffinose aldehyde and D-stachyose aldehyde) was reported during
our investgations: Kung, K. K.-Y.; Li, G.-L.; Zou, L.; Chong, H.-C.;
Leung, Y.-C.; Wong, K.-H.; Lo, V. K.-Y.; Che, C.-M.; Wong, M.-K.
Org. Biomol. Chem. 2012, 10, 925.
(18) A recent review on the synthetic methods to extend carbon
chains in carbohydrates at the anomeric positions: Monrad, R. N.;
Madsen, R. Tetrahedron 2011, 67, 8825.
(22) No aldehyde form was observed in NMR analysis of arabinose
in dioxane-d8.
Org. Lett., Vol. 15, No. 16, 2013
4131

unsuccessful,23 product 3aa was obtained in 18% yield by
the addition of 1 equiv of BF3 OEt2 (entry 2). Encouraged
by this preliminary result, we further screened boron
reagents and found that less acidic phenylboronic acid,
boric acid, and triethylborate afforded higher product
3
Table 3. Scope of Aminoalkynylation Reaction for Aldose
Substrates
yields than BF3 OEt2 (entries 3 to 5). These results suggest
3
thattheboronreagentsimproved the yield, notbyacting as
a Lewis acid, but by forming boron acetals with arabinose.
Next, weinvestigatedtheeffectsofligands for the copper
atom. Use of standard phosphine ligands did not improve
the reactivity (entries 6 and 7), and some of the bidentate
phosphine ligands (entry 8) and nitrogen-based ligands
significantly inhibited the reaction. On the other hand,
electron-deficient tris(pentafluorophenyl)phosphine sig-
nificantly improved the reactivity (entry 10).
Given that phenylboronic acid gave less satisfactory
results than boric acid24 and triethylborate (Table 1, entry
3 vs entries 4 and 5) despite its ability to form stable
complexes with the diol moieties25 of carbohydrates, we
speculated that the reversible complexation between arab-
inose and boron reagents might be important for the high-
er reactivity.26 Thus, we next examined alcohol additives
Table 2. Scope of Catalytic Aminoalkynylation Reaction for
Alkyne Substrates
a 1.2 equiv of diallylamine were used. b The stereochemistry of the
major product is only speculative.
that would enhance the reversibility of the carbohydrateÀ
boron complexation (Table 1, entries 11À13). The com-
bined use of the electron-deficient phosphine ligand and IPA
(10 equiv) led to product 3aa in 84% yield (entry 13).27,28
Diastereoselectivity, however, was not induced in most cases.
Having determined the optimal conditions, we tested the
substrate scope. The scope of alkynes was examined using
D-arabinose as an aldose substrate (Table 2). The reactivity
was not markedly influenced by the substituents of alkynes,
and in most cases the use of excess amounts of the alkyne
was not necessary to achieve high conversion. Notably,
alkynes with synthetically useful functional groups, such
as a protected aminoalcohol moiety (entry 9), an indole ring
a 3 equiv of alkyne were used. b dr: 1.9/1.
(23) We examined several Lewis acid additives, such as Al(OTf)3,
Sn(OTf)2, LiClO4, and FeCl3, but no target product was obtained in any
case.
(24) (a) Van Duin, M.; Peters, J. A.; Kieboom, A. P. G.; Van Bekkum,
H. Tetrahedron 1985, 41, 3411. (b) van den Berg, R.; Peters, J. A.; van
Bekkum, H. Carbohydr. Res. 1994, 253, 1. (c) Smith, B. M.; Owens, J. L.;
Bowman, C. N.; Todd, P. Carbohydr. Res. 1998, 308, 173. (d) Furneaux,
R. H.; Rendle, P. M.; Sims, I. M. J. Chem. Soc., Perkin Trans. 1 2000, 2011.
(e) Ricardo, A.; Carrigan, M. A.; Olcott, A. N.; Benner, S. A. Science 2004,
303, 196. (f) Sponer, J. E.; Sumpter, B. G.; Leszczynski, J.; Sponer, J.;
Fuentes-Cabrera, M. Chem.;Eur. J. 2008, 14, 9990.
(26) Our hypothesis is that the desired aminoalkynylation would
proceed from appropriate carbohydrateÀboron complexes. Reversible
carbohydrateÀboron complexation might be necessary to access such
reactive structures.
(27) Preliminary mechanistic studies and
a tentative reaction
mechanism are explained in the Supporting Information (SI)
(sections 6À8).
(25) For some representative reviews and articles on the complexa-
tion of carbohydrate and phenylboronic acid or its derivatives, see: (a)
Duggan, P. J.; Tyndall, E. M. J. Chem. Soc., Perkin Trans. 1 2002, 1325.
(b) Springsteen, G.; Wang, B. Tetrahedron 2002, 58, 5291. (c) Berube,
M.; Dowlut, M.; Hall, D. G. J. Org. Chem. 2008, 73, 6471.
(28) Control experiments suggested that boric acid does not simply
work as a transient protecting group to free hydroxy groups in unpro-
tected aldoses (see the SI, section 6).
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Org. Lett., Vol. 15, No. 16, 2013

We also examined the applicability of the developed meth-
od to the reaction using more elaborate substrates (Scheme 1).
Alkyne 2l linked to a biotin molecule was successfully used as
a nucleophile in the reaction with arabinose (1a) to afford a
biotin-conjugated32 polyol 3al in 66% yield (Scheme 1 a). The
reaction with β-D-lactose as a representative disaccharide
substrate was also attempted. Although the optimal condi-
tions for monosaccharides afforded the product in only low
yield, modification of the conditions in terms of the reaction
temperature (70 °C) and amount of boric acid (2 equiv)
successfully improved the yield. The use of 30 mol % CuBr
afforded disaccharide-conjugated product 3fj in 72% yield in
36 h (Scheme 1 b). The catalyst loading could be reduced to
10 mol % without a significant loss of reactivity (58%) if the
reaction time was extended (72 h; Scheme 1 b). Specifically,
the reaction proceeded selectively at the reducing terminal of
the disaccharide. The tolerance to multiple free hydroxy
groups and biologically significant functional groups suggests
that the developed reaction could be a potential lead method
for the concise synthesis of glycol-conjugates from sugars with
reducing terminals.
Scheme 1. Catalytic Aminoalkynylation with Elaborated
Substrates: (a) Reaction with Biotinylated Alkyne,
(b) Reaction with Disaccharide
In summary, we have developed a copper(I)-catalyzed
aminoalkynylation reaction of unprotected aldoses. This
convergent reaction can introduce molecular fragments,
including a biotinylated alkyne, to the reducing terminal of
natural carbohydrates. The catalytically generated nucleo-
phile, copper alkynide, was tolerant to multiple hydroxy
groups of the substrates and protic additives (boric acid
and IPA), yet exhibited high nucleophilicity for the desired
CÀC bond formation. Boric acid was an essential additive,
and the stereochemistry of the aldoses markedly influenced
the reactivity, suggesting that the complexation modes of
boric acid and aldoses are crucially related to the reaction
process. Elucidation of the detailed complexation modes
between boric acid and aldoses,27 improvement of the
diastereoselectivity with a wider range of aldose substrates,
and extension of this catalytic method to drug lead synthe-
sis with minimal use of protecting groups are ongoing.
(entry 10), and a ketoester equivalent (entry 11), were
competent without any loss of reactivity.
The scope of aldoses was also studied (Table 3). Among
the other three aldopentoses, the reactions with ribose
(entries 1 and 2) and xylose (entry 3) gave the target
compounds in 40À50% yield, while the reaction with
lyxose afforded the product in low yield (entry 4).29
Intriguingly, high diastereoselectivity was observed in the
reactions with ribose and lyxose, both of which have a cis
2,3-diol structure.30 As for aldohexoses, galactose (entries
5 and 6) and fucose (entries 7 to 9) gave the products in
greater than 40% yield.31 These results suggest that the
relative stereochemistry of aldoses is a crucial factor for the
reactivity and diastereoselectivity.
Acknowledgment. This work was supported by ERA-
TO from JST. Y.K. thanks JSPS for the fellowship.
Supporting Information Available. Experimental proce-
dures, syntheses and characterization of all new products,
results of control experiments and preliminary mechanis-
tic studies, and tentaive reaction mechanism. This material
is available free of charge via the Internet at http://pubs.
acs.org.
(29) Neither heating nor increasing the equivalents of boric acid
improved the reactivity.
(30) A possible mechanism for the diastereoselective induction is
explained in the SI.
(31) Reactions with typical aldohexsoses, such as D-glucose and
D-mannose, afforded the products in very low yields.
(32) For a recent review on biotinylation of bioactive molecules, see:
Trippier, P. C. ChemMedChem 2013, 8, 190.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 16, 2013
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