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Asymmetrization of meso 1 4-Enediol Ethers by Isomerization with a Chiral binapЦRhI Catalyst.

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d aldol eliminations: a) T. Uno, P. G. Schultr. J. h i . C h e i ~ .
73. h ) T. Koch. J - L . Rrymond. R. A. Lerner, ihid., in press.
Antibody-catal~ied/i-lluoro eliminations: c) K. M. Shokat. C. J. Leumann. R .
Stigau\\ar:i. 1'. C i . Schultr, ,Vu/ur.r 1989. 338. 269; d ) K. Shokat. T.Uno. P. G .
SchuIt7. .I ,~/II. ( % W I . SO(. 1994. I l h . 2261: e ) B. C'rawtt, .I.Ashley. K . D.
Jando. I) L Hoger. R . A . Lerner. /hi/.1994, 116. 6013.
[XI For carhohqdi-ate syntheses with aldolases see ref. [4c]. Leading reference for
prchiotic iiapect\ of carbohydrate chemistry: S. S. Pitsch. S. Pombo-Villar. A.
Eschcnmoser. //<'/I,.Chiin. , A ( / u 1995, 77. 2251,
141 Screening incthods l'or cdtalysis:a ) D. S.Tawfik. B. S Green. R. Chap. M. S e l ; ~
L . E\hh:iI-. PI-O. ,Vu//. A ( u d . Sci. OSA 1993. YO. 373; b) G . MacBeath. D.
Hihcrt. .I .JJII. C ' / ~ v i i .So<.. 1994. I I 6 , 6101 : c ) J. W. Lane, X. Honp. A. W.
Sc1iw;ih:icher. h i d . 1993. 1i.i. 2078. d ) H. Fcnniri, K . D. Junda. R . A . Lerner.
/ ' / o < , X u / / , l i u d &i.
1:SA 1995. 92. 2278. and references therein.
Asymmetrization of meso 1,4-Enediol Ethers
by Isomerization with a Chiral
binap- Rh' Catalyst**
the asymmetric isomerization of 1 and the related IIZC.SOsubstrates
using (Rh{(S)-binapJ(cod)]CIO, (cod = 'I .5-cy~Iooctadiene).'~~
This catalyst has been successfully employed in the catalytic
asymmetric isomerization of allylic amines.['l Although use
of this catalyst for the analogous reaction of allylic alcohols
and other allylic oxygen substrates previously met with only
limited success,[5- in the present study asymmetric isomerization of our mem substrates occurred with high enantioselectivi t y .
The products obtained can be transformed easily into the highly versatile, chiral 2,5-cyclohexadienone synthon 4" - 3 1 as well
as synthetically useful, chiral 4-rert-butyldimethylsilyloxy-2cyclohexenone (14)'" and 4-hydroxy-2-cyclohcxenone ( 15),[81
which serve as starting materials for the synthesis of the
medicinally important compounds ML-236A and FK-506. respectively.
We first treated the me.ro diol I (0.1 $1 in TH F ) with a catalytic
amount of (S)-binap/Rh' ( 5 mol Y O )At
. room temperature 1
isomerized cleanly giving the hydroxyketone ( + )-5a in quantitative yield after 40 h (Scheme 2); its optical purity was deter-
Kou Hiroya, Yuko Kurihara, and Kunio Ogasawara"
We recently reported a highly efficient enantioselective syntheof both enantiomers of the optically pure tetrahydro-endo1,4-cnethano- and tetrahydro-endo-I ,4-ethanonaphthalenones
(4a. b) by lipase-mediated asymmetrization of the corresponding mcso 1.4-enediols (I a, b). followed by a novel palladium-mediated rearrangement"1 of the resulting optically pure monoucylated intermediates (Za, b) and (3a, b) (Scheme 1 ) . Owing to
%-OR
sisIII
3
RO
1 (R = H, n=1)
6a (R =TMS. n=l. 2)
6b (R =TES, n = l , 2)
6c (R = TBS, n=l, 2)
6d (R = Me, n=1)
6e (R = Bn, n=1)
6f (R=TBS, n = l , 2;
2,3-dihydro-)
7 (R = Ac, n = l )
8 (R = MeOCH2,n=r)
HO
(CHdn
3
meso-la, b
(+)-2a, b
(-)-4a, b
6a-f
2
q
0
Q
QoHPivO
(+)-4a, b
(-)-3a, b
Scheme I
Pi\ =
pivaloyl. I a 4a: II
= I; I b
4b: ir
= 2.
its molecular bias, its a,B-unsaturated ketone functionality, and
its facile thermal extrusion of cyclopentadiene, the naphthalenone
4a allows stereoselective introduction of both nucleophiles and
electrophiles from the convex face. Since the the masked double
bonds can be regenerated 4a may serve as a chiral synthon of
2,5-cyclohe~adienone.[~~
Because we have been interested in obtaining this highly versatile chiral synthon by a nonenzymatic
procedure and because the catalytic asymmetric isomerization of
a M ~ ~ Sallylic
O
1.4-enediols such as I is not known, we examined
[*I
[**I
Pi-ul'. Dr. K Ogasawara. Prof L k K. Hiroya, Y. Kurihara
Ptiariiiac~iiticalInstitute. Tohoku University
Aohaqmi:i. Sendai 980-77 (Japan)
w e f h ... In1 codc + (22)217-6845
u-iniiil c2 I799 (1 cctu.cc.tohoku.ac j p
hinap
= P.P'-( 1 .l'-hinaphthyl-2.?'-diyl)his(diphenylph~~sphane)
R
(-)pa (R =H, n=1)
(-)-5b (R=Me,n=l)
(-)-5c
(R=TBS,n=l, 2)
____)
I
Scheme 1 TMS
sllyl.
f
=
triinethylsilyl. TES
=
(-)-5d (R=Bn, n=1)
(-)-5e (R =TBS, n = l , 2;
2,3-dihydro-)
triethqlsilyl, TBS
=
ccr.r-hut!ldiinethyl-
mined to be 43.3 ?4e p by hplc analysis ofits benzoate derivative
using a chiral column (Table 1 , entry 1). Because 1 is insoluble
in most solvents, further examination at lower temperature was
not possible, and the reactions at higher temperatures in 1 2 dichloroethane (DCE) displayed decreased selectivity (Table 1,
entries 2 and 3). Though I is soluble in acetonitrile, the reaction
did not proceed at all. We therefore transformed 1 into the
ethers 6a-f; these were treated with the same chiral catalyst at
concentrations of 0.1 -0.2 M in DCE. because the reaction in this
solvent was found to be more selective than that in THF. Of the
examined substrates the silyl ethers showed the best results:
after desilylation with aqueous HCI or nBu4iVF.['I the products
were obtained with 93-98% r e and in high yields["] (Table I ,
entries 4-9, 12, 13). The dimethyl and the dibenzyl ethers
(Table I , entries 10 and 11) also showed high selectivity; however. bisacetate 7 (R = Ac) and bis(methoxymethy1) ether 8
(R = MeOCH,) did not form any isolable product. Similar results were obtained with the 1,4-ethano counterparts (n = 2)
(Table 1. entries 5, 7, and 9). The best substrate was the bis-TBS
ether 6c (n = I ) , which afforded the crystalline silyloxyketone 5 b
(imp. 32 C, [XI;'
= - 27.0 (c = 1.08 in CHCI,)) on brief expo-
COMMUNICATIONS
employing the Saegusa conditions.[' 31 Further transformation
of 11 into allyl acetate 13 via allyl alcohol 12, followed by reductive cleavage of the bromo ether functionality" 21 yielded
monoacetate (-)-2a (m.p. 86.5-87.5"C, [a];' = - 68.78
(c = 0.96 in CHCI,)), whose enantiomer (+)-2a (m.p. 8788 "C. [a];' = + 70.05 (c = 1.02 in CHCI,)) was previously obtained by enzymatic transesterification of 1 .[Ia1 Quite similarly.
the configuration of 1,4-ethano-bridged hydroxyketone (-)-5 a
( n = 2 ) was determined by conversion into (-)-4b, which was
identical with an authentic material obtained by the enzymatic
procedure." b1
On the other hand. a solution of the ketosilyl ether (-)-5b
(96% re) in freshly distilled diphenyl ether was refluxed for
20 min to afford (Rj-4-terr-butyldimethylsilyloxy-2-cyclohexenone [(R)-14]rs1
= + 109.0 (c = 1.1 5 in CHCI,) (96.4% ee by
hplc); literature value for the ( S ) enantiomer:[""] [a], =
- 11 5.9 (c = 1.06 in CHCI,)) in 95 Yoyield. The absolute configuration of (Rj-14 was confirmed by further transformation into
(R)-4-hydroxy-2-cyclohexenone [(R)-l5lr8] ([x];' = 109.0
(c = 1.29. CHCI,); literature value for the ( S )enantiomer:[tlal
[a], = - 110 (c = 0.92 in CHCI,)) in 9 4 % yield on exposure to
' ~:~19) (Scheme 3).
hydrofluoric acid (48 "/o) in a ~ e t o n i t r i l e [(1
Although we could not explain the inversion of enantioselectivity on going from the free diol 1 to the bisethers 6a-f in the
presence of the same catalyst, the isomerization of the meso
bisethers may be rationalized by a mechanism involving a
suprafacial 1,3-hydrogen shift." 51 This hypothesis was supported by a deuterium labeling experiment using [D,]6c. This 58,88deuterium-labeled compound afforded the rearranged product
7B,88-deuterium-labeled hydroxyketone [D,]Sa cleanly after
desilylation without scrambling or loss of the original deuterium
atoms. As shown in Scheme 4, oxidative addition occurs first to
Table 1. Asymmetriration o f n w o diol 1 and ethers 6a-f by (S)-binap;Rh' in DCE
bl] .
Entry Substr
1
2
3
4
5
6
7
8
9
10
11
12
13
Cat.
T
[mol%] [h]
I(n=i)
l(n=l)
1 (n = I )
6 a (n = I )
6 a (n = 2)
6 b 0 1 =1)
6 b (n = 2)
6 c (11 = I )
6 c ( n = 2)
6d (n = 1 )
6e(n=1)
6 f (n =1)
6 f (n = 2)
5.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
Product
/
Yield
["/.I
2 5 C 15(+)-5a(n=l)
25 C 100 ( + ) - 5 a ( 1 1 = 1 )
reflux 15 ( t)-5a (n = 1 )
reflux 14 ( - ) - 5 a (n = I )
reflux 11 (-)-Sa ( n = 2)
reflux 16 (-)-Sa ( n = 1)
reflux 12 (-)-5a (n = 2)
reflux 17 (-)-Sb (11 = 1)
reflux 12 (-)-5b (11 = 2)
50 C 12 ( - ) - S C (n = 1 )
50 C 40 ( - ) - 5 d ( n = 1 )
reflux 20 (-)-Se ( n =1)
reflux 16 ( - ) - 5 e (n = 2)
Selectivity
[% ??I
-100
43.3[e]
28.0
38.3[e]
99.6 [b] 16.9 [el
= l o 0 [h]
93.5 [el
96.8 [b] 93.6 [el
85.8 [b] Y7.5 [el
94.0 [b] 96.0 [el
94.9 [c] 96.1 [el
78.6 [c] 96.0 [el
91.4
73.0 [f]
66.6[d] 72.8[f]
88.7 [c] 93.7 [el
85.2 [ c ] 93.9 [el
[a] DCE = 1,2-dichloroethane:in entry 1 THF was used instead of DCE. [b] Yield
after conversion of the product into hydroxyketone 5 a by desilylation (dil. HCI in
T H F or nBu,NF in THF). [c] Yield after conversmn of the product into the sllyloxyketone 5 b by treatment with dilute HCI. [d] About 30% of 6 e was recovered
unchanged. [el Enantiomeric excess was determined by converting the product into
its benzoate derivative and analyzing by HPLC using a chiral column
(CHIRALCEL 0D:elution. iPrOHlhexane. 1 :99 v:v). [Q Enantiomer~cexcesswas
estimated by comparison of the optical rotation values with those of authentic
material.
sure (ca. 5 min) to nBu,NF in T H F at 0 'C (Table 1, entry 8).
Interestingly, the enantioselectivity exerted by diol 1 and ethers
6a-d is inverted. Moreover, the asymmetrization occurred with
excellent selectivity with the 2,3-dihydro substrates (6f: n = 1,
2 ) , indicating the 2,3-olefin functionality is not critical for the
reaction. It is particularly significant that this first successful
asymmetrization of the meso allylic oxygen substrates proceededwith yields and selectivities comparable to those of the enzymatic reaction (Scheme 2 and Table 1).
The absolute configuration of the 1,4-methano-bridged hydroxyketone 5a (n = 1) was determined by transforming (-)-5a
(n = 1) into the chiral2,5-cyclohexadienonesynthon (+)-4a[" 21
via the monoacetate (-)-2a; ( - ) - 5 b (n = 1) was converted into
the known chiral4-trrt-butyldimethylsilyl-2-cyclohexenone
(R)14["] and 4-hydroxy-2-cyclohexenone (R)-15 (Scheme 3).
Thus, ( - j-5a (96% re) was first treated with NBS["] to give
bromo ether 9 in 92% yield, which then was dehydrogenated to
give enone 1 1 in 80 Yooverall yield via the silyl enol ether 10 by
+
oxidative
addition
[Dz16c
TBSO
17
16
reductive
elimination
TBSO
19
'?$
(-)-5a (R = H)
(-)-5b (R = TBS)
TMSO
0
9
10
h
OH
0
11
5a
Scheme 4.
Br
0
14 (R=TBS)
3
15 (R=H)
0
12 (R = H)
13 (R = AC)
eG
AcO
(-)-2a
Scheme 3 . a) N-Brotnosuccinimide (1.1 equlv). CH2Ci,, 0 C. 1 h ; 91.5%; b) iPrNEI, (11 equiv). T M S O T ~(2 equiv), CH,CI,, 0 C, 2.5 h; C) Pd(oAc), (1.1 equiv),
MeCN, room temperature (RT). 26 h; 80%) based on 9: d) NaBH, (1.5 equiv),
CeCI3.7H,0 (1.5 equw). -78 C , 4.5 h: 92%: e) Ac,O (2equiv), Et,N (3equiv).
4-dimethylaminopyridine (cat.), CH,CI,, 0-25°C. 12 h , f) Z n (8 equiv). AcOH
.
20 mi":
(15 equiv). MeOH. reflux. 7 h; 76% based on 1 2 ; ~2) 6 0 " ~dlphenylether,
95%: h) H F (45%):MeCN ( 1 . 5 b : v ) . 0 C. 4 h; 96%.
form the Rh"' complex 16, which in turn is isomerized by 1,3metal migration to give the alternative Rh"' complex 17 carrying
a silyl en01 ether functionality. Subsequent reductive elimination produces the Rh' complex 18 and release of the Rh' catalyst
yields the disilyl ether 19.
In conclusion, we have established a new highly efficient,
enantioselective entry to the versatile chiral building blocks tetrahydro-endo-l,4-methano-and tetrahydro-endo-l,4-ethanonaphthalenones by isomerization of the bissilyl ethers of nzeso
allylic 1.4-enediols using a cationic chiral binap-Rh' catalyst.
This result is remarkable for a number of reasons: 1) This is the
first application of a catalytic asymmetric isomerization to an
allyl ether substrate that reaches a practical level of enantioseIeCtiVity. 2) This is the first SUCCeSSfUl asymmetrization of a meso
substrate by a catalytic isomerization. 3) The chemical and
COMMUNICATIONS
enantiomeric efficiencies of this method are fully comparable to
those of the enzymatic procedure. 4) This method can provide
highly vcrsatilc cyclohexenone chiral synthons very efficiently.
5 ) The reaction mechanism has been proven to include a
suprafacial 1.3-hydrogen migration pathway.
E.uprrinzcntal Procedure
Tranzforiiiatioii o i 6 c into 5 b . To a stirred solution of 6 c (405 mg. 1.0 mmol) in
I,?-dichloroetliane (4.6 m L ) was added [Rh:(S)-hinap)(cod)]ClO~ (18.6 mg.
19.9 inniol) i n 1 .Z-dichloroethane (0.5 mL) dropwise at room temperature under
argon ;ind the niiytiire w'as relluxed for 17 11. The solvent was evaporated. the
residue dissolved 111 T H F ( 5 m L ) . and the resulting solution stirred with nBu,NF
( I 0 M in 7 IfF, 1 0 inl,) at 0 ' C for 5 min. The solution was diluted with ether and
washed succeaiwly with water and brine. dried over MgSO,. and concentrated
under reduced pressure. The residue was chromatographed on silica gel (EtOAc:
hexanc 1.9) to gi%e5b a s colorless crystals (276 mg, 94.9%) (96.1 % LT). A single
recrystallmition from hexane g i v e the optically pure material (99.5 "/o e e ) as colorless prism\. m p 32 C. [r];' = - 27.0 ((, = 1.08 in CHCI,).
Received: June 9. 1995 [Z80731E]
German version: ,4i?gew. Chrm. 1995. 107. 2445-2448
Keywords: asymmetric syntheses
rhodium compounds
. catalysis
isomerizations
.
[ I ] a ) For 4 a . see- S Takano. Y. Higashi. T. Kamikubo. M Moriya. K.
Ogasauara. . S ~ n r h e i . \1993.948- 950; h) for 4b, see: M. Moriya, T. Kamikubo.
K. Ogasriwara. r/7id 1995. 1x7- 190.
121 S Takano, M . Moriya. T. Kamikuho. K. Hiroya. K. Ogasawara. TLrruhedron
L c t t 1993. 34. 8 4 8 5 ~X48X.
[3] Some rcprc\ent;itive examples, see' a ) K. Ogasawara. Pirre App/. Clim?. 1994,
Oh. 21 10 2122. h) S. Takano. M. Moriya, Y. Higashi. K. Ogasawara. J. Chrm.
.SO( C'hf~n?.
('onin~un.1993, I l l - 1 7 8 : c ) S . Takano, M . Moriya. K. Ogasawara.
ihrd 1993, 614 615; d) S. Takano, Y. Higashi. T. Kamikuho, M.Moriya. K.
Ogaaawara. /hid 1993. 788-~789:e) S. Takano. M Moriya. K. Ogasawara.
. S j , n / c , ~ 1993.601
t
-602. f ) S. Takano. T. Kamikuho. M. Moriyd. K. Ogasdwara.
. S j n t h a i s 1994. 601 - 604. g) T Kamikuho. K . Ogasawara, Clim?. Lctr. 1995.
9 5 Y6: h) T. Kamikubo. K . Ogasawara. Tetrahedron Lett. 1995. 36. 1685
[4]
[S]
161
[7]
[XI
[Y]
[lo]
16x8.
A Mi>,irhita. A. Yasuda, H. Takaya, K. Toriumi. T. Ito, T. Souchi. R.
.I)
.
1980, 102. 7932-7934; h) A. Miyashita. H. Takaya.
Noyori, J .4,ri. C ' h i v ~ ?Soc.
T. Souchi. K Noyori. Tt,rmhedrn,i 1984. 40, 1245-1253; c) M . Takaya. K.
M;c\hima. K . Koyano. M . Yagi, H . Kumobayashi. T. Taketomi. S. Akutagdwa.
K Noyori. ,L 0,:p. Chmn 1986. 51, 629- 635.
Pertinent reviews, see: a ) S. Otsuka. K. Tani in A.svmnietric Swt/ie.si.s. Vo/. S
(Ed ..I.11 Morrison), Academic Press, New York. 1985. pp. 171-191: h) R.
Noyori. M. Kitamura in ModiJrri Sjntheru Methods. Val. S (Ed : R. Schefford),
Springer. tieidelherg. 1989. pp. I15 198: c) S. Otsuka. K. Tani. SjiirhesO 1991.
665 6x1).
M K i t a i n i ~ r ~K.~ .Monake, R. Noyori. H. Yakaya. Tt.rrrihcdron Lrfr. 1987, 28.
4719 4720
tflicienl catal>tic production of achirdl enols using Rhl-diphosphane complexea. see S. H . Bergens. B. Bosnich. J: An?. Chjlenz. Sot. 1991. 113. 958-967.
a ) S. 1. Dani\hefsky. B. Simoneau, J. Ani. Cheni. Soc. 1989,111.2599-2604: b)
A B. Jones. M. Yamaguchi. A. Patten, S J. Danishefsky. J. A . Ragan. D. B.
Smith. S. L Schreiher. J. Org. Chrnz. 1989. 54. 17-19.
Attempts 10 isolate the products as the silyl enol ethers in pure form failed since
:I con\idei-;ihle umount of the ketones ( > 20%) always formed before the reaction was quenched.
I Kuw;ijini:i. E. Nahamura, M. Shimizu. .I Am. Chmi. Snc. 1982, 104. 1025io?n
1. E. Audia. L. Boisvert. A D. Patten. A. Villalobos, S. J. Danishefsky. J.
O I , ~ .' h ~ 1989.
~ n i 54. 3738 3740. h) M. C. Carreno. J. L. Ruano. M. Garrido.
3 i P. Run. G. Solladie. Trrrahcr/ron Lett. 1990. 31. 6653-6656.
[I?] C'f. S TakLino. K Inomata. K Ogasawara. Chcn. Letr 1989. 359 -362.
[13] Y 110. T Ilirao. T. Saegusa. J. Org. C h m . 1978. 43. 1011 1013.
[14] R . F Ncwton. D. P Reynolds. M. A . Finch. F. D . Kelly. S . M. Roberts, Tctro/ic</rnrl Lvti. 1979. 3981 3982.
[15] ('I R. Nohori. Tt~frirh~~drnn
1994. Sf). 4259-4292.
[I I]
;I)
Radiofrequency Encoded Combinatorial
Chemistry * *
K. C. Nicolaou,* Xiao-Yi Xiao,* Zahra Parandoosh,
Andrew Senyei, Michael P. Nova"
Combinatorial chemistry"' has recently been recognized as a
powerful tool in drug discovery"] and materials science.[31Although the potential of this method in these areas is enormous,
its current scope is limited by several factors."' Particularly
prohibitive is the lack of a general encoding system for following
the synthetic sequence leading to the chemical constructs so that
structural characterization can be facilitated. Despite the introduction of several encoding.[41physicaL1'] and deconvolution 161
techniques for identification of members in a chemical library,
serious practical issues still remain and a more general and practical solution to this problem is needed.
We introduce here a new concept for encoding combinatorial
chemical libraries based on radiofrequency signals and semiconductor memory devices using a multifunctional Microreactor.
Radiofrequency Encoded Combinatorial (RECTM)chemistry.
as this new method is termed, combines recent advances in microelectronics, sensors, and chemistry and uses a Single or Multiple Addressable Radiofrequency Tag (SMARTTM) semiconductor unit['] to record encoding and other relevant information along the synthetic pathway. This allows identification
of library members by
SMART iMemory
retrieval of the recordand
iMulfi-informnation
ed history and other
Storage Uecice
specific information relating to the construction of each compound. The practicability of the concept and
the validity of the principles of REC chemistry
are demonstrated here
with a small peptide
library generated by
the "split and pool"
--.L,.,l
IIICLIIUU.'
TerrtaGel
Polymer
Read
181
-
Inert.
Kemvvabie
Porvcts Wall
A SMART MicroreactorTM (Fig. 1) was
Fig. 1. Schematic cross-hection of 21 Microreconstructed from the
actor used in REC ~ l i c m i s,t r ~iclvinc
~.on
fOl1oWing Units: 1) a
SMART multi-information storage devices.
small
(8 x 1 x 1 mm)
semiconductor SMART memory device capable of receiving.
storing, and emitting radiofrequency signals instantaneously
from a distance of 75 - 150 mm ; 2) several TentaGel-like polymer
beads carrying an acid-cleavable linker; and 3) ii chemically inert,
surrounding porous support. A representative REC chemistry
[*] Prof Dr. K. C. Nicolaou"'
Department of Chemistry. The Scripps Research Institiire
10666 N. Torrey Pines Road. La Jolla. CA 92037 ( U S 4 1
and
Department of Chemistry and Biochemistry
Universit) of California. San Diego
9500 Gilman Drive. La Jolla. CA 92093 (USA)
Telefax: Int. code (619)554-6738
e-mail: knicolaouiti ucsd.edu
+
Dr M. P. Nova. Dr. X.-Y Xiao. Dr. 2. Parandoosh, Dr. A. Senyei
IRORI Quantum Microchemistry
11025 N. Torrey Pines Road, La Jolla, CA 92037 ( U S A )
Telefax: Int. code (619)546-1300
e-mail: N0VAIRORI:ii AOL
K. C. N. is an advisor to IRORI Quantuni Microchemistry.
We thank Chris Claihorne for the computer-generated drawings.
+
['I
[**I
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