Complete Retention of Configuration in a Cobaloxime ?-Cation-Mediated Cyclization of an (ω-hydroxy-β-hydroxyalkyl)cobaloxime

Full text of DOI:10.1021/jo961794w

242
J . Org. Chem. 1997, 62, 242-243
Sch em e 1
Com p lete Reten tion of Con figu r a tion in a
Coba loxim e π-Ca tion -Med ia ted Cycliza tion
of a n
(ω-Hyd r oxy-â-h yd r oxya lk yl)coba loxim e
Lana M. Grubb and Bruce P. Branchaud*
Department of Chemistry, University of Oregon,
Eugene, Oregon 97403-1253
Received September 19, 1996
In 1961, Lenhert and Hodgkin reported that the
vitamin B12 coenzyme contains a novel carbon-cobalt
bond.1 The unusual chemical reactions catalyzed by
coenzyme B12-dependent enzymes have stimulated nu-
merous studies of the chemical reactions of the C-Co
bond in coenzyme B12, in other cobinamides, and in
coenzyme B12 model complexes such as the cobaloximes.
Most of the mechanistic studies have focused on the
radical chemistry of the C-Co bond.2 Over the past
decade, the radical chemistry of the C-Co bond in B12-
like compounds has been used to develop useful synthetic
organic methods.3
The C-Co bond also displays ionic reactivity. The
C-Co bond can provide anchimeric assistance for the
departure of a leaving group in the â position to form a
hyperconjugated cationic intermediate best described as
a cobaloxime π-cation. Several studies have focused on
the structure and reactivity of cobaloxime π-cations.4 It
has been known for over 20 years that cobaloxime
π-cations can be captured by oxygen and nitrogen nu-
cleophiles. For example, (â-hydroxyalkyl)- and (â-alkoxy-
alkyl)cobaloximes can undergo acid-catalyzed â-hetero-
atom exchange with oxygen and nitrogen nucleophiles.5
Recently, we reported the reaction of cobaloxime π-cat-
ions with carbon nucleophiles, the first examples of
carbon-carbon bond formation.6
was only 37%,8 the retention of configuration result in
this case and other incisive mechanistic studies of this
type of reaction9 indicated its considerable potential for
applications in organic synthesis.
As part of our research program to explore the reactiv-
ity and synthetic potential of cobaloxime π-cations we
decided to examine the stereochemistry of a cyclization
reaction of an (ω-hydroxy-â-hydroxyalkyl)cobaloxime to
form a cyclic ether. Racemic (2,5-dihydroxypentyl)-
cobaloxime (3) was reported to undergo silica gel-medi-
ated cyclization to form (tetrahydrofurfuryl)cobaloxime
(4) (eq 2).10 In this paper, we report the stereochemical
To date there has been only one report of the stereo-
chemistry of reactions of cobaloxime π-cations. In 1972,
the solvolysis of homochiral (2-acetoxypropyl)cobaloxime
in benzyl alcohol was reported to proceed with retention
of configuration (eq 1).7 This observation supported the
outcome of that reaction (Scheme 1).
Treatment of L-glutamic acid ((S)-5) with NaNO2 and
HCl in H2O gave an intermediate lactone11 that was
reduced to (S)-1,2,5-pentanetriol using LiAlH4,12 followed
by acetonide protection of the 1,2 diol (catalytic p-
toluenesulfonic acid (p-TsOH) in dry acetone)13 to give
(S)-1,2-O-isopropylidene-1,2,5-pentanetriol ((S)-6) in 19%
overall yield for three steps from (S)-5. Treatment of
(S)-6 with benzoyl chloride and pyridine in CH2Cl2
produced (S)-1,2-O-isopropylidene-5-O-benzoyl-1,2,5-pen-
tanetriol,14 which was treated with 0.1 N HCl in MeOH/
H2O to remove the acetonide to provide (S)-5-O-benzoyl-
1,2,5-pentanetriol ((S)-7) in 82% overall yield for two
steps from (S)-6. Treatment of (S)-7 with p-toluene-
postulated intermediacy of cobaloxime π-cations in alco-
holyses of (2-acetoxyalkyl)cobaloximes. Although the
yield of pure, isolated [2-(benzyloxy)propyl]cobaloxime
* To whom correspondence should be addressed. Phone: (541) 346-
4627. Fax: (541) 346-4645. E-mail: bbranch@oregon.uoregon.edu.
(1) Lenhert, P. G.; Hodgkin, D. C. Nature 1961, 192, 937-38.
(2) (a) Golding, B. T. Chem. Br. 1990, 950-954. (b) Garr, C. D.;
Finke, R. G. Inorg. Chem. 1993, 32, 4414-21. (c) Waddington, M. D.;
Finke, R. G. J . Am. Chem. Soc. 1993, 115, 4629-40. (d) Ng, F. T. T.;
Rempel, G. L.; Mancuso, C.; Halpern, J . Organometallics 1990, 9,
2762-72.
(3) Branchaud, B. P.; Friestad, G. K. Vitamin B12. In Encyclopedia
of Reagents for Organic Synthesis; Paquette, L. A., Ed.; J ohn Wiley
and Sons: Chichester, West Sussex, 1995; pp 5511-5514 and references
cited therein.
(4) (a) Brown, K. L.; Ramamurthy, S.; Marynick, D. S. J . Organomet.
Chem. 1985, 287, 377-394. (b) Brown, K. L.; Ramamurthy, S.
Organometallics 1982, 1, 413-415. (c) Silverman, R. B.; Dolphin, D.
J . Am. Chem. Soc. 1976, 98, 4626-4633.
(5) Ecker, H.; Ugi, I. J . Organomet. Chem. 1976, 118, C55.
(6) Gage, J . L.; Branchaud, B. P. J . Org. Chem. 1996, 61, 831-837.
(7) Golding, B. T.; Sakrikar, S. J . J . Chem. Soc., Chem. Commun.
1972, 1183-1184.
(8) Personal communication from Bernard T. Golding.
(9) Golding, B. T.; Holland, H. L.; Horn, U.; Sakrikar, S. Angew.
Chem., Int. Ed. Engl. 1970, 9, 959-960.
(10) Parfenov, E. A.; Yurkevich, A. M. Zh. Obshch. Khim. 1972, 42,
2350.
(11) Herdeis, C. Synthesis 1986, 232-233.
(12) Brunner, H.; Lautenschlager, H. Synthesis 1989, 706-709
(13) Hayashi, H.; Nakanishi, K.; Brandon, C.; Marmur, J . J . Am.
Chem. Soc. 1973, 95, 8749-8757.
(14) Mashimo, K.; Sato, Y. Tetrahedron 1970, 26, 803-812.
S0022-3263(96)01794-X CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 2, 1997 243
Sch em e 2
sulfonyl chloride (TsCl), triethylamine, and 4-(N,N-
dimethylamino)pyridine (DMAP) in CH2Cl2 at -20 °C
followed by treatment with NaCo(dmgH)2py in MeOH
under standard conditions to form alkyl cobaloximes15
provided [(S)-2-hydroxy-5-O-benzoylpentyl]cobaloxime ((S)-
8) in 52% overall yield for two steps from (S)-7. The
benzoate group in (S)-8 was hydrolyzed with 1% NaOH
in MeOH to produce cobaloxime (S)-3, which was not
isolated but was converted directly into cobaloxime (S)-4
by acidification to pH 6.4-6.8 with a standardized HCl
solution and solid pyridinium p-toluensulfonate (PPTS).
1
The structure of cobaloxime (S)-4 was confirmed by H
NMR comparison to an authentic racemic sample, (R,S)-
4, prepared from (()-tetrahydrofurfurylbromide16 and by
comparison to literature data.17 Cobaloxime (S)-4 was
photochemically cross-coupled with styrene in 95% EtOH
for 48 h18 to give alkene (S)-10 in 51% isolated yield after
chromatography.
tioenriched tetrahydyro-2-furoic acid (R)-11 was obtained
through a brucine resolution.22 Borane reduction of (R)-
11 using BH3‚SMe2 in THF gave (R)-12 in moderate
yield.23 Tosylate formation followed by displacement of
the tosylate with LiBr in acetone gave (R)-13. Reaction
of (R)-13 with NaCo(dmgH)2py in MeOH produced co-
baloxime (R)-4. Cross-coupling of (R)-4 with styrene gave
alkene (R)-10, whose absolute configuration was cer-
tain.24 Alkene (R)-10 was analyzed by chiral HPLC. The
major peak in the analysis of (R)-10 was opposite to that
observed for alkene (S)-10 obtained by the cobalt-medi-
ated cyclization shown in Scheme 1. This result, com-
bined with the other results reported herein, establishes
that the cyclization of cobaloxime (S)-3 to form co-
baloxime (S)-4 is stereospecific and proceeds with reten-
tion of configuration.
The stereoselectivity of the cyclization of (S)-3 to form
(S)-4 was determined by chiral HPLC.19 Racemic diol
(R,S)-7 was prepared from racemic 1,2,5-pentanetriol,
which was prepared by a literature method.20 Racemic
diol (R,S)-7 was used to determine the retention times
for each enantiomer of 7 on the chiral HPLC column. The
enantiomeric excess of (S)-7 was determined to be 95.9%
ee ((0.3%).21 Racemic alkene (R,S)-10 was prepared by
cross coupling of racemic (R,S)-4 (prepared as described
for (S)-10 above) with styrene. Racemic alkene (R,S)-10
was used to determine the retention times for each
enantiomer of 10 on the chiral HPLC column. Alkene
(S)-10 obtained from the cobalt-mediated cyclization
shown in Scheme 1 was determined to have an enantio-
meric excess of 93.8% ((0.1%).
The data presented in the preceding paragraph estab-
lish that the cyclization of cobaloxime π-cation 9 is
stereospecific, but they do not establish whether the
reaction proceeds with complete retention or with com-
plete inversion of configuration. To determine this it was
necessary to obtain an authentic sample of either (R)-10
or (S)-10 by an independent method (Scheme 2). Enan-
Ack n ow led gm en t. Professor J ames D. White and
his research group at Oregon State University provided
access to their polarimeter and instruction in its use.
Professor David A. Evans and Dr. J erry A. Murry at
Harvard University obtained the first chiral HPLC data
for this project and provided invaluable advice on chiral
HPLC. Dr. Timothy Weakley obtained the X-ray crystal
structure mentioned in ref 24. This research was
supported by NSF CHE 9423782.
(15) Schrauzer, G. N.; Deutsch, E. J . Am. Chem. Soc. 1969, 91,
3341-3350.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for synthetic operations and chiral HPLC, and charac-
terization data for all compounds are available (12 pages).
(16) Smith, L. H. Organic Syntheses; Wiley: New York, 1964;
Collect. Vol. III, pp 793-794.
(17) Mock, W. L.; Bieniarz, C. Organometallics 1984, 3, 1279-1284.
(18) Branchaud, B. P.; Meier, M. S. J . Org. Chem. 1989, 54, 1320-
1326.
J O961794W
(19) Chiral HPLC analysis was performed using a Chiralcel OD-H
analytical column and monitored at 254 nm. Experimental details are
in the Supporting Information.
(22) Belanger, P. C.; Williams, H. W. R. Can. J . Chem. 1983, 61,
1383-1386.
(23) Alajarin, R. et al. J . Med. Chem. 1995, 38, 2830-2841.
(24) In addition to the configuration information reported in refs
22 and 23, an X-ray crystal structure of the brucine salt used for the
resolution of 11 was obtained. The X-ray crystal structure confirmed
the configuration shown.
(20) Wilson, C. L. J . Chem Soc. 1945, 49.
(21) HPLC separation of 7 on the column was not complete and some
shouldering was observed. This could lead to a slight overestimation
of the enantiomeric purity of 7.