Asymmetric dihydroxylations of 1-substituted (E)-and (Z)-3-methylpent-2-en- 4-ynes: Full compliance with the sharpless mnemonic re-established and embellished

Article abstract of DOI:10.1021/ol103063t

Asymmetric dihydroxylations ("ADs") of the pentenynyl chlorides (E)-and (Z)-1 or the pentenyne-based ester (Z)-3 in the presence of (DHQ) ₂-containing ligands delivered diol stereoisomers (2R,3S)-2, (2R,3R)-2, and (3S,4R)-4, respectively. The A

Full text of DOI:10.1021/ol103063t

ORGANIC
LETTERS
2011
Vol. 13, No. 5
1020–1023
Asymmetric Dihydroxylations of
1-Substituted (E)- and (Z)-3-Methylpent-2-
en-4-ynes: Full Compliance with the
Sharpless Mnemonic Re-established
and Embellished
†
Heike Burghart-Stoll, Oliver Bohnke, and Reinhard Bruckner*
‡
,†
€
€
€
Institut fu€r Organische Chemie und Biochemie, Albert-Ludwigs-Universitat,
Albertstr. 21, 79104 Freiburg im Breisgau, Germany, and Gymnasium Goetheschule,
Schu€tzenstr. 1, 37574 Einbeck, Germany
reinhard.brueckner@organik.chemie.uni-freiburg.de
Received December 17, 2010
ABSTRACT
Asymmetric dihydroxylations (“ADs”) of the pentenynyl chlorides (E)- and (Z)-1 or the pentenyne-based ester (Z)-3 in the presence of (DHQ)2-containing
ligands delivered diol stereoisomers (2R,3S)-2, (2R,3R)-2, and (3S,4R)-4, respectively. The ADs of pentenynyl ethers (E)-10 and (Z)-12, respectively, have
the same stereochemical preference under analogous conditions; these reattributions correct previous reports of the contrary. The Sharpless mnemonic
rationalizes all these results implying that each substrate prefers a Sharpless/Norrby instead of a Chapleur orientation in the transition state.
Recently1 we have shown that in the presence of Sharp-
less’ ligands (DHQ)2PHAL (which is responsible for stereo-
control effected by AD-mix R2) or (DHQ)2AQN3 the
1-chlorinated 3-methylpent-2-en-4-ynes (E)- and (Z)-1
are dihydroxylated asymmetrically.4 This furnished chloro-
diols (2R,3S)- and (2R,3R)-2, respectively, in yields of up
to 73% (Scheme 1). Enantioselectivities reached 85% ee
with (E)-1 as the substrate and 91% ee starting from (Z)-1.
The configurational proof in the (E)-series was based on an
X-ray structural analysis and the proof in the (Z)-series on
a correlation with a compound derived from the (E)-series.
Another 1-substituted 3-methylpent-2-en-4-yne, namely
ester (Z)-3, reacted with the same facial selectivity with
Sharpless’ AD-mix R as chloride (Z)-1, proceding via
dihydroxyester (3S,4R)-4 directly5 to the hydroxylactone
(4S,5R)-56 (Scheme 2). The correct configuration of the
latter was not recognized correctly7 before we found that
ester (Z)-6 and AD-mix R gave the identically configured
lactone (4S,5R)-8 via dihydroxyester (3S,4R)-7.8 This was
shown by an X-ray analysis of the derived bromobenzoate
†
€
Albert-Ludwigs-Universitat.
‡ Gymnasium Goetheschule.
(1) Burghart-Stoll, H.; Kapferer, T.; Bruckner, R. Org. Lett. (DOI:
10.1021/OL103061g).
€
(2) (a) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.;
Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768–2771 (in the presence
€
of MeSO2NH2). (b) Footnote 6 in Jeong, K.-S.; Sjo, P.; Sharpless, K. B.
Tetrahedron Lett. 1992, 33, 3833–3836 (in the absence of MeSO2NH2).
(3) (a) Becker, H.; Sharpless, K. B. Angew. Chem. 1996, 108, 447–449.
(b) Becker, H.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1996, 35,
448–451.
r
10.1021/ol103063t
Published on Web 01/27/2011
2011 American Chemical Society

Scheme 1. AD Reactions of the Methylpentenyne-Based
Chlorides (E)- and (Z)-1
Scheme 2. AD Reactions of the Methylpentenyne-Based Ester
(Z)-3 and the Related Ester (Z)-68
a K3Fe(CN)6 (3.0 equiv), K2OsO2(OH)4 (1.0 mol %), dihydroquini-
dine-based ligand (2.0 mol %), buffer (3.0 equiv each of NaHCO3 and
K2CO3), and MeSO2NH2 (1.0 equiv).
a K3Fe(CN)6 (3.0 equiv), K2OsO2(OH)4 (2.0 mol %), (DHQ)2PHAL
(10 mol %), K2CO3 (3.0 equiv), and MeSO2NH2 (1.0 equiv). b Prepared
from (Z)-3: [R]2D0 = -4.9 (c = 0.83 in CHCl3); prepared from (2R,3R)-2:
[R]2D0 = -5.6 (c = 0.5 in CHCl3). c K3Fe(CN)6 (3.0 equiv), K2OsO2-
(OH)4 (0.8 mol %), (DHQ)2PHAL (1.6 mol %), K2CO3 (3.0 equiv), and
MeSO2NH2 (1.0 equiv).
(4S,5R)-9. A proof of the steric course of the AD reaction
of ester (Z)-3 was obtained by an independent synthesis1 of
the same lactone (4S,5R)-5 from the chlorodiol (2R,3R)-2.
Disconcertingly, the stereoselectivity of our AD (E)-1 þ
AD-mix R f (2R,3S)-2 differed from the selectivities
reported for ADs of certain ethers, which share an (E)-
configured methylpentenyne with our substrate: AD-mix
R was claimed to convert ethers (E)-10a-dinto diols (2R,3R)-
11a-d (Scheme 3, top).9 Similarly, our ADs (Z)-1 þ AD-
mix R f (2R,3R)-2 and (Z)-3 þ AD-mix R f (3S,4R)-
4/(4S,5R)-5 had opposite stereoselectivities as the ADs of
several ethers, which share a (Z)-configured methylpente-
nyne with our substrates: AD-mix R allegedly transforms
ethers (Z)-12a and b into dihydroxyethers (2R,3S)-13a and
b, respectively (Scheme 4, bottom).10 Incidentally Nakatani
et al. (Scheme 3, bottom) contradicted this (without
recognizing it) when they dihydroxylated the PMB ether
(E)-10d in the presence of AD-mix β and isolated diol
Scheme 3. AD Reactions of the Methylpentenyne-Based Ethers
(E)-109 and (E)-1210 from the Literature11,12
(4) (a) Lohray, B. B. Tetrahedron: Asymmetry 1992, 3, 1317–1349. (b)
Johnson, R. A.; Sharpless, K. B. In Asymmetric Catalysis in Organic
Synthesis; Ojima, I., Ed.; VCH: New York, 1993; pp 227-272; (c) Kolb,
H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94,
2483–2547. (d) Poli, G.; Scolastico, C. Methoden Org. Chem. (Houben-
Weyl), 4th ed. -, Vol. E21e; Helmchen, G., Hoffmann, R. W., Mulzer, J.,
Schaumann, E., Eds.; Thieme: Stuttgart, 1995; pp 4547-4598. (e)
Salvadori, P.; Pini, D.; Petri, A. Synlett 1999, 1181–1190. (f) Johnson,
R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 357-389. (g) Bolm, C.;
(2R,3R)-11d, which was dextrorotatory.11 According to
~
Hildebrand, J. P.; Muniz, K. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: Weinheim, 2000; pp 399-428. (h) Krief, A.;
Colaux-Castillo, C. Pure Appl. Chem. 2002, 74, 107–113. (i) Kolb, H. C.;
Sharpless, K. B. In Transition Metals for Organic Synthesis; Beller, M.,
Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2, pp 275-298. (j) Noe,
M. C.; Letavic, M. A.; Snow, S. L.; McCombie, S. Org. React. 2005, 66,
109–625. (k) Zaitsev, A. B.; Adolfsson, H. Synthesis 2006, 1725–1756.
€
Tietze and Gorlitzer the same diol (2R,3R)-11d stemmed
from (E)-10d and AD-mix R but was levorotatory.9
€
Ancillary findings by Tietze and Gorlitzer increased our
worries. Ethers (E)-12a-d and AD-mix R reportedly gave
the diols (2S,3S)-13a-d (Scheme 3, center);10 this amounts
to a reversal of the asymmetric induction in the ADs (E)-
10a-d þ AD-mix R f (2R,3R)-11a-d9 (Scheme 3, top).
Why an sp-bonded arene moiety in (E)-12a-d instead of
an sp-bonded H-atom in (E)-10a-d should have such an
€
(5) Method: (a) Harcken, C.; Bruckner, R. Angew. Chem. 1997, 109,
€
2866–2868. Harcken, C.; Bruckner, R. Angew. Chem., Int. Ed. 1997, 36,
€
2750–2752. (b) Kapferer, T.; Bruckner, R. Eur. J. Org. Chem. 2006,
2119–2133.
(6) The enantiopurity of this specimen was determined by chiral
HPLC after tert-butyldiphenylsilylation (see Supporting Informations).
€
€
(7) Bohnke, O. Dissertation, Universitat Freiburg, 2002, pp 63,
124, 151.
€
€
(8) Kapferer, T.; Bruckner, R.; Herzig, A.; Konig, W. A. Chem.;
Eur. J. 2005, 11, 2154–2162.
(12) The AD reaction of the para-methoxybenzoate of the alcohol,
which underlies the ethers (E)-10a-d, in the presence of AD-mix R gave
a levorotatory triol with 86% ee; the “configuration of the major
enantiomer was assigned tentatively by application of the Sharpless
mnemonic” as (2S,3S), i.e. differently than Tietze’s (2R,3R)-10a-d:
Alvarez, S.; Alvarez, R.; de Lera, A. R. Tetrahedron Asymmetry 2004,
15, 839–846. Our results are analogous and therefore corroborate de
Lera’s conclusion.
€
(9) Tietze, L. F.; Gorlitzer, J. Liebigs Ann. Recl. 1997, 2221–2225.
€
(10) Tietze, L. F.; Gorlitzer, J. Synthesis 1997, 877–885.
(11) (a) Nakatani, K.; Okamoto, A.; Saito, I. Angew. Chem. 1997,
109, 2881–2884. Nakatani, K.; Okamoto, A.; Saito, I. Angew. Chem.,
Int. Ed. 1997, 36, 2794–2797. (b) Nakatani, K.; Okamoto, A.; Matsuno,
T.; Saito, I. J. Am. Chem. Soc. 1998, 120, 11219–11225.
Org. Lett., Vol. 13, No. 5, 2011
1021

Scheme 4. AD Reactions of the Methylpentenyne-Based Ethers
(Z)-109 and (Z)-1210 from the Literature14
Scheme 5. AD Reactions Reassigned I: Proof That (E)-10a and
AD-Mix R React Differently than Published
a [R]2D0 = þ23.6 (c = 1.1 in CHCl3). b Compatibility of this sense of the
specific rotation with the depicted configuration is excluded by our
work. c [R]2D0 = -22.0 (c = 1.0 in CHCl3).
substrates-that the stereodescriptors of the resulting diols
must be reversed (Schemes 5 and 6, respectively). More-
over we proved the correctness of the stereodescriptors of
diol (2S,3S)-13a15-18 obtained from ether (E)-12a and of
diol (2S,3R)-11a19,20 obtained from ether (Z)-10a.
Chlorodiol (2S,3R)-21 and sodium 4-methoxyphenoxide
in ethanol21 at reflux gave the PMP-containing diol
(2R,3R)-11a (Scheme 5). It was dextrorotatory. Diol 11a
prepared from the PMP ether (E)-10a and AD-mix R was
levorotatory9 and therefore (2S,3S)-11a.22 By analogy, diols
(-)-11b-c of Scheme 3 should be (2S,3S)-configured, too.
effect was not clear.13 The same structural change seemed
to swap the asymmetric inductions in the AD-mix
R-mediated dihydroxylations of the Csp-arylated ethers
(Z)-12a,b [f (2R,3S)-13a and b, respectively;10 Scheme 4,
bottom] compared to the Csp-unsubstituted ethers (Z)-10a,b
[f (2R,3S)-11a and b, respectively;9 Scheme 4, top].
The pivotal role of Sharpless ADs in organic synthesis4
compelled us to check these matters by correlating selected
€
Tietze/Gorlitzer diols with ours. We showed both for
ether (E)-10a and ether (Z)-12a,b-i.e., for representative
(18) (S)-6-(Benzyloxy)-2,5,7,8-tetramethylchromane-2-carbalde-
hyde is dextrorotatory (589 nm, c = 5.2 in CHCl3) according to Cohen,
N.; Lopresti, R. J.; Saucy, G. J. Am. Chem. Soc. 1979, 101, 6710–6716.
(13) There are AD reactions, however, where remote anisyl groups
modify the extent of enantiocontrol, albeit not its direction: (a) Corey,
E. J.; Guzman-Perez, A.; Noe, M. C. Tetrahedron Lett. 1995, 36, 3481–
3484. (b) Corey, E. J.; Guzman-Perez, A.; Noe, M. C. J. Am. Chem. Soc.
1995, 117, 10805–10816. (c) Corey, E. J.; Noe, M. C.; Guzman-Perez, A.
J. Am. Chem. Soc. 1995, 117, 10817–10824. (d) Corey, E. J.; Noe, M. C.;
Ting, A. Y. Tetrahedron Lett. 1996, 37, 1735–1738. (e) Corey, E. J.; Noe,
M. C. J. Am. Chem. Soc. 1996, 118, 11038–11053.
(14) The AD reaction of the para-methoxybenzoate of the alcohol,
which underlies the ethers (Z)-10a,b, with AD-mix R gave a levorotatory
triol with 56% ee; the “absolute configuration of the major enantiomer
was assigned tentatively by application of the Sharpless mnemonic” as
(2S,3R), i.e. differently than Tietze’s (2R,3S)-12a,b: Alvarez, S.; Alvarez,
R.; de Lera, A. R. Tetrahedron Asymmetry 2004, 15, 839–846. Our
results are analogous and therefore corroborate de Lera’s conclusion.
€
(19) We proved the steric course of Tietze’s and Gorlitzer’s
transformation10 (Z)-10a þ AD-mix R f (-)-(2S,3R)-11a (Scheme 4,
top) by establishing that the enantiomeric product (2R,3S)-11a
(preparation: Scheme 6, top) was dextrorotatory: (-)-(2S,3R)-11a
(82% ee) showed [R]2D0 = -20.0 (c = 1 in CHCl3) while (2R,3S)-11a
(92% ee) showed [R]D20 = þ22.3 (c = 0.37 in CHCl3).
(20) The facial selectivity of the functionalizations of (Z)-10a,b with
AD-mix R (Scheme 4, top9) lacked experimental support. The resulting
diols were Sonogashira-coupled to provide diols9 13a,b with the same
relative configurations as the ones obtained from (Z)-12a,b and AD-mix
R in one step (Scheme 4, bottom10). However, differently than the
authors believed (ref 10 and footnote 2 therein) no specific rotations
were measured on the Sonogashira route (ref 22b). This left the absolute
configuration of these specimens of (-)-ul-11a and (-)-ul-b unproved.
(21) Procedure: Gandolfi, C. A.; Di Domenico, R.; Spinelli, S.;
Gallico, L.; Fiocchi, L.; Lotto, A.; Menta, E.; Borghi, A.; Rosa, C. D.;
Tognella, S. J. Med. Chem. 1995, 38, 508–525.
€
(15) We proved the steric course of Tietze’s and Gorlitzer’s
transformation9 (E)-12a þ AD-mix R f (-)-(2S,3S)-13a (Scheme 3,
center) by gaining the enantiomeric product (þ)-(2R,3R)-13a by a
Sonogashira coupling between diol (þ)-(2R,3R)-11a (proof of the 3D
structure of the latter: Scheme 5, top) and 1-iodo-2,5-dimethoxy-3,4,6-
trimethylbenzene.18 (2S,3S)-13a (>95% ee) exhibited [R]2D0 = -13.5 (c
= 1 in CHCl3) whereas (2R,3R)-13a (92% ee) exhibited [R]2D0 = þ11.4 (c
= 0.3 in CHCl3); i.e., these compounds had inverse rotational powers.
(22) (a) The 3D structure of the dihydroxylation product (-)-
(“2R,3R”)-11a should have emerged from the X-ray analysis of crystals
of the monosulfonate derived with (þ)-camphorsulfonyl chloride.9 The
ORTEP plot depicted the compound as 14 (ref 22b, p 72), but the
corresponding valence formula was flawed as 15 (ref 22b; p 70)
and published as such.9 (b) Gorlitzer, J. Dissertation, Universitat
€
€
€
Gottingen, 1997.
(16) The steric course of the transformation (E)-12b þ AD-mix R f
(2S,3S)-13b (Scheme 3, center) was established unambiguously by
acetonide formation, desilylation, condensation with (-)-camphanoyl
chloride, and an X-ray structural analysis of the resulting ester.10
(17) Differently than stated10 no proof was provided for the stereo-
selectivity of the transformation (E)-12c þ AD-mix R f (2S,3S)-13c
(Scheme 3, center): (2S,3S)-13c had been converted into what was drawn
as the S-enantiomer of 6-(benzyloxy)-2,5,7,8-tetramethylchromane-2-
carbaldehyde in seven steps,10 but this assignment was not corroborated
experimentally.18
ꢀ
€
(23) (a) Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroder, G.;
Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968–1970. (b) Sharpless,
K. B.; Amberg, W.; Beller, M.; Chen, H.; Hartung, J.; Kawanami, Y.;
€
Lubben, D.; Manoury, E.; Ogino, Y.; Shibata, T.; Ukita, T. J. Org.
Chem. 1991, 56, 4585–4588. (c) Reference 2b. (d) Kolb, H. C.;
Andersson, P. G.; Sharpless, K. B. J. Am. Chem. Soc. 1994, 116,
1278–1291. (e) Vanhessche, K. P. M.; Sharpless, K. B. J. Org. Chem.
1996, 61, 7978–7979. (f) Fristrup, P.; Tanner, D.; Norrby, P.-O. Chirality
2003, 15, 360–368.
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Org. Lett., Vol. 13, No. 5, 2011

Scheme 6. AD Reactions Reassigned II: Proof That (Z)-12a and
AD-Mix R React Differently than Published
a [R]2D0 =þ22.3 (c=0.37inCHCl3).b [R]D20 =þ13.6 (c=0.33inCHCl3).
c Compatibility of this sense of the specific rotation with the depicted
configuration is excluded by our work. d [R]D20 = -12.6 (c = 1.0 in CHCl3).
According to Scheme 6 chlorodiol (2S,3S)-21 was con-
verted via its PMP-ether (2R,3S)-11a21 and a Sonogashira
coupling with 1-iodo-2,5-dimethoxy-3,4,6-trimethylben-
zene into the dextrorotatory diol (2R,3S)-13a. Diol 13a
prepared from the arylated PMP-ether (Z)-12a and AD-
mix R was levorotatory10 and hence (2S,3R)-configured.
In summary it has been shown that all heterosubstituted
(E)- and (Z)-methylpentenynes, which have been vic-dihy-
droxylated to date under the influence of DHQ-containing
ligands are attacked as if preferring a “Sharpless/Norrby
orientation” in any of the Sharpless-mnemonic transition
states23 16-19 (Figure 1) such that steric hindrance in
zone 1, which is (the most) repulsive, is minimized.
With respect to alkenes containing a trisubstituted CdC
bond we reduced the number of “Chapleur oriented”24 AD
substrates by (E)-10a-d and (Z)-12a,b. When/if one does
Figure 1. Stereoselectivities of ADs of standard substrates with a
trisubstituted CdC bond in the presence of DHQ-containing
ligands (top; DHQD-containing ligands attack from downside) and
of isobutyl angelate in the presence of (DHQD)2PHAL (bottom).
(24) A “Chapleur orientation” in the transition state of an AD
represents the optimum of maximized bonding in zone 2 and minimized
strain in zone 1.25
(25) Moitessier, N.; Henry, C.; Len, C.; Chapleur, Y. J. Org. Chem.
2002, 67, 7275–7282.
(26) Shao, H.; Rueter, J. K.; Goodman, M. J. Org. Chem. 1998, 63,
5240–5244.
not accept the revised configuration25 of the diol produced
from isobutyl angelate and AD-mix β,26 this implies a
“Chapleur orientation” 2025 (Figure 1) in the transition
state,27-29 the only AD reaction affecting a “Chapleur
oriented” trisubstituted CdC bond, of which we are aware
may concern an R-alkylidenelactone.30 It seems reasonable,
accordingly, to base synthetic planning entailing an AD of a
trisubstituted CdC bond on “Sharpless/Norrby orienta-
tions” 16-19 of the substrate and to specify that the sp2-
bonded H-atom shall be in the (most) hindered position (1).
(27) (a) Menthyl angelates undergo ADs with stereoselectivities
matching “Sharpless/Norrby orientations” in the transition state:
Torres-Valencia, J. M.; Cerda-Garcıa-Rojas, C. M.; Joseph-Natan, P.
Tetrahedron: Asymmetry 1998, 9, 757–764. (b) The same is true for
disubstituted angelates: Nicolaou, K. C.; Yue, E. W.; La Greca, S.;
Nadin, A.; Yang, Z.; Leresche, J. E.; Tsuri, T.; Naniwa, Y.; De
Riccardis, F. Chem.;Eur. J. 1995, 1, 467–494.
(28) (a) AD stereoselectivities of monocarbamoylated alkyl angelates in
line with “Sharpless/Norrby orientations” in the transition state but with-
out proofs: Claudel, S.; Olszewski, T. K.; Mutzenardt, P.; Aroulanda, C.;
Coutrot, P.; Grison, C. Tetrahedron 2006, 62, 1787–1798. (b) dto. regarding
ADs of a mono- and a dimethylated ethyl angelate: Stritzke, K.; Schulz, S.;
Nishida, R. Eur. J. Org. Chem. 2002, 3884–3892.
(29) The diols from AD-mix R and 2-(trimethylsilyl)ethyl angelate
(Liu, H.; Jensen, K. G.; Tran, L. M.; Chen, M.; Zhai, L.; Olsen, C. E.;
Søhoel, H.; Denmeade, S. R.; Isaacs, J. T.; Christensen, S. B. Phyto-
chemistry 2006, 67, 2651-2658) or a monosubstituted angelate [Xie, W.;
Ding, D.; Zi, W.; Li, G.; Ma, D. Angew. Chem. 2008, 120, 2886-2890;
Xie, W.; Ding, D.; Zi, W.; Li, G.; Ma, D. Angew. Chem., Int. Ed. 2008, 47,
2844-2848 (Supporting Information)] were drawn-without proofs-as
if emerging from “Chapleur orientated” substrates.
Acknowledgment. The authors thank Dr. Thomas
Netscher (DSM, Basel) for donations of (E)- and (Z)-3-
methylpent-2-en-4-yn-1-ol.
Supporting Information Available. Experimental pro-
cedures, characterization data, and copies of NMR spec-
tra. This material is available free of charge via the
Internet at http://pubs.acs.org.
(30) Curran, D. P.; Ko, S.-B. J. Org. Chem. 1994, 59, 6139–6141.
Org. Lett., Vol. 13, No. 5, 2011
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