Synthesis of cyclic 1-alkenylboronates via Zr-mediated double functionalization of alkynylboronates and sequential Ru-catalyzed ring-closing olefin metathesis

Article abstract of DOI:10.1021/ol400896u

Synthesis of novel cyclic 1-alkenylboronates is accomplished through the zirconium-mediated regio- and stereoselective double functionalization of 1-alkynylboronates and the subsequent ruthenium-catalyzed ring-closing metathesis (RCM). The obtained substituted cyclic 1-alkenylboronates are transformed into o-terphenyl and triphenylene derivatives.

Full text of DOI:10.1021/ol400896u

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Synthesis of Cyclic 1‑Alkenylboronates
via Zr-Mediated Double Functionalization
of Alkynylboronates and Sequential
Ru-Catalyzed Ring-Closing Olefin
Metathesis
Yasushi Nishihara,*,†,‡ Masato Suetsugu,† Daisuke Saito,† Megumi Kinoshita,† and
Masayuki Iwasaki†
Division of Earth, Life, and Molecular Sciences, Graduate School of Natural Science and
Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530,
Japan, and Japan Science and Technology Agency, ACT-C, 4-1-8 Honcho, Kawaguchi,
Saitama 332-0012, Japan
ynishiha@okayama-u.ac.jp
Received April 2, 2013
ABSTRACT
Synthesis of novel cyclic 1-alkenylboronates is accomplished through the zirconium-mediated regio- and stereoselective double functionalization
of 1-alkynylboronates and the subsequent ruthenium-catalyzed ring-closing metathesis (RCM). The obtained substituted cyclic 1-alkenylboronates
are transformed into o-terphenyl and triphenylene derivatives.
Cyclic alkenylboron compounds are highly valuable
synthetic intermediates, particularly with regards to CꢀC
bond formation through Pd-catalyzed SuzukiꢀMiyaura
cross-coupling reactions,1 giving rise to useful organic
compounds showing biological activity such as Manz-
amine A and its derivatives.2 Several synthetic routes to
cyclic 1-alkenylboronates have been realized through
DielsꢀAlder reactions of 1,3-dienyl-2-boronates with
alkynes3 or of 1-alkynylboronates with dienes,4 halogenꢀ
boron exchange reactions,5,6 and transition-metal-catalyzed
dehydrogenative borylations of cyclic alkenes.7 However,
we often encounter difficulties in obtaining cyclic 1-alke-
nylboronates by utilizing transition-metal-catalyzed addi-
tion reactions of the boron-containing compounds to
the internal alkynes8 due to the less common availability
ꢀ
(7) (a) Olsson, V. J.; Szabo, K. J. Angew. Chem., Int. Ed. 2007, 46, 6891–
6893. (b) Kondoh, A.; Jamison, T. F. Chem. Commun. 2010, 46, 907–909.
(8) For examples of dimetalation of the internal alkynes, see: Silyl-
borylation: (a) Nozaki, K.; Wakamatsu, K.; Nonaka, T.; Tuckmantel,
W.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1986, 27, 2007–2010.
(b) Suginome, M.; Nakamura, H.; Ito, Y. Chem. Commun. 1996, 2777–
2778. (c) Ohmura, T.; Oshima, K.; Suginome, M. Chem. Commun. 2008,
1416–1418. Stannylborylation: (d) Sharma, S.; Oehlschlager, A. C.
Tetrahedron Lett. 1988, 29, 261–264. (e) Onozawa, S.; Hatanaka, Y.;
Sakakura, T.; Shimada, S.; Tanaka, M. Organometallics 1996, 15, 5450–
5452. Diboration: (f) Ishiyama, T.; Matsuda, N.; Miyaura, N.; Suzuki,
A. J. Am. Chem. Soc. 1993, 115, 11018–11019. Thioborylation:
(g) Ishiyama, T.; Nishijima, K.; Miyaura, N.; Suzuki, A. J. Am. Chem.
Soc. 1993, 115, 7219–7225.
† Okayama University.
‡ Japan Science and Technology Agency.
(1) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
(2) Winkler, J. D.; Londregan, A. T.; Ragains, J. R.; Hamann, M. T.
Org. Lett. 2006, 8, 3407–3409.
(3) Kamabuchi, A.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1993,
34, 4827–4828.
(4) Hilt, G.; Smolko, K. I. Angew. Chem., Int. Ed. 2003, 42, 2795–2797.
(5) Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. Synthesis
2000, 778–780.
(6) Takahashi, K.; Takagi, J.; Ishiyama, T.; Miyaura, N. Chem. Lett.
2000, 126–127.
r
10.1021/ol400896u
XXXX American Chemical Society

of cyclic alkynes9 or benzyne10 as the precursors. On the
other hand, the versatility and synthetic applicabi-
lity of the ring-closing olefin metathesis (RCM) reac-
tion in the construction of functionalized carbocycles
and heterocycles has been thoroughly demonstrated.11
Along this line, recent advances in the synthesis of cyclic
1-alkenylboronates using the Ru-catalyzed RCM of di-
enylboronates provided cyclic 1-alkenylboronates with
high versatility.12 Recently, we have succeeded in the
synthesis of various multisubstituted alkenylboronates
regio- and stereoselectively, derived from alkynylboro-
nates13 and a low-valent ziroconocene complex.14 Herein,
we disclose that the cyclic 1-alkenylboronates are
synthesized in high yields via RCM of highly allylated
alkenylboronates given by double functionalization of
1-alkynylboronates as the starting materials.
Similarly, analogous tetrasubstituted alkenylboronates
2bꢀ2e were obtained in moderate to high yields by double
allylation or vinylation/allylation sequences. Perfect con-
trol of the stereochemistry of (Z)-alkenylboronates 2aꢀ2e
is highly important for further cyclization reaction leading
to the formation of the desired cyclic 1-alkenylboronates.
Scheme 1. Zirconocene-Mediated Synthesis of Tetrasubstituted
Alkenylboronates 2aꢀ2e
The tetrasubstituted alkenylboronates 2aꢀ2e were pre-
pared in good to excellent yields by the reaction of the
starting 1-alkynylboronates 1a and 1b with the low-valent
zirconocene complex, followed by sequential introduction
of various allyl and/or vinyl moieties.15 For instance,
treatment of phenyl-substituted 1-alkynylboronate1awith
Cp2ZrCl2/2nBuLi (Negishi’s reagent)16 in the presence of
PnBu3 afforded the stabilized zirconacyclopropene I,17
which upon sequential double allylation generated 2a in
60% yield with perfect stereoselectivity as shown in
Scheme 1. To the best of our knowledge, zirconacyclopro-
penes as the intermediate species are believed to be fleeting
and difficult to observe,18 although related complexes are
known.19 Excellent selectivity forming 2 is attributed to the
regioselective formation of zirconacyclopentene II (allyl)
or II0 (vinyl) bearing the boron moiety in the R-position,
from which a smooth β-oxygen elimination gave rise to the
alkenylzirconocene intermediate III.
Next our investigations focused on the regio- and stereo-
selective preparation of multisubstituted alkenylboron-
ates through double allylation of zirconacyclopentenes
(Scheme 2).20 To our delight, upon treatment with
Cp2ZrCl2/2EtMgBr (Takahashi’s reagent),21 1-alkynyl-
boronate 1a afforded the zirconacyclopentene as an inter-
mediate regioselectively, which was subjected to double
allylation to give 2f and 2g in 53% and 58% yields,
respectively. The obtained alkenylboronates 2aꢀ2g are
1
fully characterized by GC-MS, H, and 13C{1H} NMR
(9) Krebs, A.; Wilke, J. Top. Curr. Chem. 1983, 109, 189–233.
(10) Yoshida, H.; Okada, K.; Kawashima, S.; Tanio, K.; Ohshita, J.
Chem. Commun. 2010, 46, 1763–1765.
spectra as well as elemental analyses.
(11) For recent reviews on olefin metathesis, see: (a) Cusak, A.
Chem.;Eur. J. 2012, 18, 5800–5824. (b) Hassan, H. M. A. Chem.
Commun. 2010, 46, 9100–9106. (c) van Otterlo, W. A. L.; de Koning,
C. B. Chem. Rev. 2009, 109, 3743–3782. (d) Monfette, S.; Fogg, D. E.
Chem. Rev. 2009, 109, 3783–3816. (e) Donohoe, T. J.; Fishlock, L. P.;
Procopiou, P. A. Chem.;Eur. J. 2008, 14, 5716–5726.
(12) (a) Renaud, J.; Ouellet, S. G. J. Am. Chem. Soc. 1998, 120, 7995–
7996. (b) Renaud, J.; Graf, C.-D.; Oberer, L. Angew. Chem., Int. Ed.
2000, 39, 3101–3104.
Scheme 2. Synthesis of Tetrasubstituted Alkenylboronates 2f
and 2g via Double Allylation of Zirconacyclopentene
(13) For a recent review on alkynylboron compounds, see: Jiao, J.;
Nishihara, Y. J. Organomet. Chem. 2012, 721ꢀ722, 3–16.
(14) (a) Nishihara, Y.; Miyasaka, M.; Okamoto, M.; Takahashi, H.;
Inoue, E.; Tanemura, K.; Takagi, K. J. Am. Chem. Soc. 2007, 129,
12634–12635. (b) Nishihara, Y.; Okada, Y.; Jiao, J.; Suetsugu, M.; Lan,
M.-T.; Kinoshita, M.; Iwasaki, M.; Takagi, K. Angew. Chem., Int. Ed.
2011, 50, 8660–8664.
(15) Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron
Lett. 1994, 35, 5685–5688.
(16) Negishi, E.-i.; Cederbaum, F. E.; Takahashi, T. Tetrahedron
Lett. 1986, 27, 2829–2832.
(17) Takahashi, T.; Suzuki, N.; Kageyama, M.; Kondakov, D. Y.;
With the doubly allylated alkenylboronate 2a in hand,
we next established the reaction conditions for RCM.
The reactions were routinely carried out in the presence
of 1ꢀ5 mol % of Grubbs second-generation catalyst A
Hara, R. Tetrahedron Lett. 1993, 34, 4811–4814.
(18) For example: (a) Takahashi, T.; Swanson, D. R.; Negishi, E.
Chem. Lett. 1987, 623–626. (b) Buchwald, S. L.; Nielsen, R. B. Chem.
Rev. 1988, 88, 1047–1058. (c) Johnson, S. A.; Liu, F.-Q.; Suh, M. C.;
Zurcher, S.; Haufe, M.; Mao, S. S. H.; Tilley, T. D. J. Am. Chem. Soc.
2003, 125, 4199–4211. (d) Imabayashi, T.; Fujiwara, Y.; Nakao, Y.;
Sato, H.; Sakaki, S. Organometallics 2005, 24, 2129–2140.
(19) Miller, A. D.; McBee, J. L.; Tilley, T. D. J. Am. Chem. Soc. 2008,
130, 4992–4999.
(20) Ben-Valid, S.; Quntar, A. A. A.; Srebnik, M. J. Org. Chem. 2005,
70, 3554–3559.
(21) Takahashi, T.; Nitto, Y.; Seki, T.; Saburi, M.; Negishi, E. Chem.
Lett. 1990, 2259–2262.
B
Org. Lett., Vol. XX, No. XX, XXXX

(Mes = 2,4,6-Me3C6H2),22 an efficient catalyst for
RCM,23 in CH2Cl2 at 25 or 40 °C. As shown in Table 1,
the RCM catalyzed by Ru-complex A efficiently converted
the substrate 2a into the desired six-membered carbocyclic
1,4-cyclohexadienylboronate 3a in 82% yield (Table 1,
entry 1). Owing to a suppression of the intermolecular
reaction, the diluted solution (0.01 M) of 2a gave the better
yield (Table 1, entry 2). A catalyst loading reduced to
1.0 mol % also generated 3a in comparable yields (Table 1,
entries 3 and 4). Finally, we found that the inexpensive
first-generation Grubbs catalyst B24 also furnished 3a in
95% yield. This is the first example of the Ru-catalyzed
RCM of tetrasubstituted alkenylboronates into cyclic
1-alkenylboronates bearing the substituents in the R-position
of the boron functionality.
alkenylboronate 2d (for a five-membered ring) and 2f
(for an eight-membered ring). Unfortunately, however,
no desired cyclic 1-alkenylboronates were isolated under
the conditions described in Table 1. For example, when 2d
and 2f were treated with catalyst B, the complete consump-
tion of 2d gave the complex mixture and the starting
compound 2f remained unreacted, respectively.
Table 2. Synthesis of Cyclic 1-Alkenylboronates 3aꢀc via RCM
of Alkenylboronates 2aꢀca
entry
substrate
product
yield (%)b
Table 1. Effect of Reaction Parameters on RCM of the
Tetrasubstituted Alkenylboronate 2aa
1
2
3
2a
2b
2c
3a
3b
3c
95
94
94
a All reactions employed alkenylboronates 2 (2.0 mmol) in CH2Cl2
(200 mL, 0.01 M) at rt. b Isolated yields.
The successful transformation of tetrasubstituted alke-
nylboronates 2 into six-membered cyclic ones 3 encour-
aged us to investigate the synthesis of 1,2-disubstituted 1,4-
cyclohexadienes, o-terphenyls, and triphenylenes. In the
field of organic materials science, the design and charac-
terization of polycyclic aromatic hydrocarbons (PAHs),
which exhibit superior electronic, optical, and/or self-assem-
bling properties, have been studied intensively.25 Hence,
efficient synthetic methods leading to functionalized PAHs
are expected to assist the rapid developments of PAH-based
functional materials.26 The Pd-catalyzed SuzukiꢀMiyaura
cross-coupling reactions of 3a with aryl iodides could be an
efficient method for the formation of a wide variety of
PAHs. The results of cross-couplings and the aromatization
of 3a are also summarized in Scheme 3. The resultant cyclic
alkenylboronate 3a was efficiently cross-coupled with var-
ious aryl iodides to give the corresponding 1,2-disubstituted
1,4-cyclohexadienes 4aꢀd in excellent yields in the
entry
catalyst
X (mol %)
Y (M)
temp (°C)
yield (%)b
1
2
3
4
5
A
A
A
A
B
5.0
5.0
1.0
1.0
1.0
0.10
0.01
0.01
0.01
0.01
40
40
40
25
25
82
94
92
99
95
a All reactions employed alkenylboronate 2a (0.1 mmol). b GC yields.
Under the optimized reaction conditions, a series of
alkenylboronates 2aꢀc were subjected to the Ru-catalyzed
RCM. The results are summarized in Table 2. The six-
membered cyclic 1-alkenylboronates 3aꢀc were formed in
excellent yields. Since an RCM forming five- to seven-
membered rings has been known to proceed,11 we at-
tempted the RCM of the synthesized tetrasubstituted
(22) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953–956. (b) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.;
Wilhelm, T. E.; Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs,
R. H. J. Am. Chem. Soc. 2003, 125, 2546–2558. (c) Vougioukalakis,
G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746–1787.
€
€
(25) (a) Watson, M. D.; Fechtenkotter, A.; Mullen, K. Chem. Rev.
€
2001, 101, 1267–1300. (b) Wu, J.; Pisula, W.; Mullen, K. Chem. Rev.
2007, 107, 718–747. (c) Wu, D.; Zhi, L.; Bodwell, G. J.; Cui, G.; Tsao, N.;
€
Mullen, K. Angew. Chem., Int. Ed. 2007, 46, 5417–5420. (d) Lorenz,
(23) (a) Yoshida, K.; Imamoto, T. J. Am. Chem. Soc. 2005, 127,
10470–10471. (b) Yoshida, K.; Kawagoe, F.; Iwadate, N.; Takahashi,
H.; Imamoto, T. Chem.;Asian J. 2006, 1, 611–613. (c) Yoshida, K.;
Horiuchi, S.; Iwadate, N.; Kawagoe, F.; Imamoto, T. Synlett 2007,
1561–1564. (d) Yoshida, K.; Toyoshima, T.; Imamoto, T. Chem.
Commun. 2007, 3774–3776. (e) Yoshida, K.; Takahashi, H.; Imamoto,
T. Chem.;Eur. J. 2008, 14, 8246–8261. (f) Yoshida, K.; Shishikura, Y.;
Takahashi, H.; Imamoto, T. Org. Lett. 2008, 10, 2777–2780. (g) Yoshida,
K.; Narui, R.; Imamoto, T. Chem.;Eur. J. 2008, 14, 9706–9713.
(h) Yoshida, K.; Toyoshima, T.; Imamoto, T. Bull. Chem. Soc. Jpn.
2008, 81, 1512–1517. (i) Yoshida, K.; Kawagoe, F.; Hayashi, K.;
Horiuchi, S.; Imamoto, T.; Yanagisawa, A. Org. Lett. 2009, 11, 515–
518. (j) Takahashi, H.; Yoshida, K.; Yanagisawa, A. J. Org. Chem. 2009,
74, 3632–3640. (k) Yoshida, K.; Shida, H.; Takahashi, H.; Yanagisawa,
A. Chem.;Eur. J. 2011, 17, 344–349. (l) Yoshida, K.; Hayashi, K.;
Yanagisawa, A. Org. Lett. 2011, 13, 4762–4765.
ꢁ
U. J.; Solca, N.; Lemaire, J.; Maitre, P.; Dopfer, O. Angew. Chem., Int.
Ed. 2007, 46, 6714–6716. (e) Rouhanipour, A.; Roy, M.; Feng, X.;
€
€
Raeder, H. J.; Mullen, K. Angew. Chem., Int. Ed. 2009, 48, 4602–4604.
(f) Kitagawa, Y.; Segawa, H.; Ishii, K. Angew. Chem., Int. Ed. 2011, 50,
9133–9136.
(26) (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons; Wiley:
New York, 1997. (b) Boorum, M. M.; Scott, L. T. In Modern Arene
Chemistry; Astruc, D., Ed.; Wiley-VCH: Weinheim, 2002: pp 20ꢀ31.
(27) For recent selected examples, see: (a) Lee, J. J.; Yamaguchi, A.;
Alam, M. A.; Yamamoto, Y.; Fukushima, T.; Kato, K.; Takata, M.;
Fujita, N.; Aida, T. Angew. Chem., Int. Ed. 2012, 51, 8490–8494. (b)
Osawa, T.; Kajitani, T.; Hashizume, D.; Ohsumi, H.; Sasaki, S.; Takata,
M.; Koizumi, Y.; Saeki, A.; Seki, S.; Fukushima, T.; Aida, T. Angew.
Chem., Int. Ed. 2012, 51, 7990–7993. (c) Tatum, L. A.; Johnson, C. J.;
Fernando, A. A. P.; Ruch, B. C.; Barakoti, K. K.; Alpuche-Aviles,
M. A.; King, B. T. Chem. Sci. 2012, 3, 3261–3264. (d) Paquette, J. A.;
Yardley, C. J.; Psutka, K. M.; Cochran, M. A.; Calderson, O.; Williams,
V. E.; Maly, K. E. Chem. Commun. 2012, 48, 8210–8212.
(24) (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc.
1996, 118, 100–110. (b) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs,
R. H. Angew. Chem., Int. Ed. Engl. 1995, 34, 2039–2041.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 3. Synthesis of Symmetrical and Unsymmetrical
1,2-Diaryl-1,4-cyclohexadienes 4aꢀd and o-Terphenyls 5aꢀc
Scheme 5. An Alternative Synthesis of Triphenylenes (6) by
Pd-Catalyzed Annulation via CꢀH Functionalization of 4d
Scheme 6. Rhodium-Catalyzed 1,4-Addition of Cyclic
Alkenylboronate 3a
Scheme 4. Synthesis of Triphenylene (6) by Oxidative Cyclization
of 5a
In order to demonstrate the utility of the synthesized
cyclic 1-alkenylboronates, conjugate addition of 3a to
2-cyclohexenone catalyzed by Rh was conducted and the
subsequent DDQ oxidation in CH2Cl2 afforded 7 in 49%
yield (Scheme 6).31
In summary, we have developed the regio- and stereo-
selective synthesis of tetrasubstituted alkenylboronates by
a zirconocene-mediated stepwise allylation or vinylation
of 1-alkynylboronates and zirconacyclopentene. The sub-
sequent Ru-catalyzed RCM gave rise to the formation
of six-membered cyclic 1-alkenylboronates that are not
available by other methods. Current efforts to expand the
scope of 1-alkynylboronates as well as to elucidate the
application to the synthesis of various PAHs are in
progress.
presence of a catalytic amount of PdCl2(dppf) under the
basic conditions. Furthermore, oxidation of the obtained
4aꢀc with DDQ in CH2Cl2 furnished the o-terphenyls
5aꢀc in 93, 98, and 93% yields, respectively.
Triphenylene derivatives are known to be applied to
several functional organic materials such as the discotic
liquid crystals.27,28 When 5a was treated with MoCl5,29
synthesis of triphenylene (6) was accomplished, albeit in
33% yield (Scheme 4).
Since a direct oxidative cyclization of o-terphenyl was
known to give a complex mixture due to the severe reac-
tion conditions and the presence of many CꢀH bonds
in the molecule,26 selective synthesis of triphenylene (6)
was examined by the Pd-catalyzed CꢀH functionalization
of 4d. The once isolated 4d was treated with a catalytic
amount of Pd(OAc)2 under basic conditions,30 followed by
DDQ oxidation to give the desired products 6 in 63% yield
(Scheme 5).
Acknowledgment. The authors gratefully thank Ms.
Megumi Kosaka and Mr. Motonari Kobayashi at the
Department of Instrumental Analysis, Advanced Science
Research Center, Okayama University for the measure-
ments of elemental analyses and the SC-NMR Laboratory
of Okayama University for the NMR measurements. Y.N.
also acknowledges The Sumitomo Foundation.
(28) For recent reviews, see: (a) Laschat, S.; Baro, A.; Steinke, N.;
Giesselmann, F.; Hagele, C.; Scalia, G.; Judele, R.; Kapatsina, E.; Sauer,
S.; Schreivogel, A.; Tosoni, M. Angew. Chem., Int. Ed. 2007, 46, 4832–
4887. (b) Sergeyev, S.; Pisula, W.; Geerts, Y. H. Chem. Soc. Rev. 2007,
36, 1902–1929. (c) Kumar, S. Chem. Soc. Rev. 2006, 35, 83–109.
(d) O’Neill, M.; Kelly, S. M. Adv. Matter 2003, 15, 1135–1146.
´
(29) King, B. T.; Kroulık, J.; Robertson, C. R.; Rempala, P.; Hilton,
C. L.; Korinek, J. D.; Gortari, L. M. J. Org. Chem. 2007, 72, 2279–2288.
Supporting Information Available. Copies of 1H NMR
and 13C{1H} NMR spectra for all the new compounds, as
well as details on experimental procedures and character-
ization data. This material is available free of charge via
the Internet at http://pubs.acs.org.
ꢀ
(30) For reviews, see: (a) Echavarren, A. M.; Gomez-Lor, B.;
ꢀ
ꢀ
Gonzalez, J. J.; de Frutos, O. Synlett 2003, 585–597. (b) Alberico, D.;
Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174–238. (c) Lyons,
T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147–1169.
(31) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997,
16, 4229–4231. (b) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.;
Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579–5580. (c) Hayashi, T.;
Yamasaki, K. Chem. Rev. 2003, 103, 2829–2844.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX