Iodoolefinic polypropionate building blocks from vinyl silanes with control of geometry by solvent and by neighboring group participation

Article abstract of DOI:10.1016/j.tetlet.2010.11.001

Iododesilylation of trisubstituted (Z)-silyl olefins proceeds with retention of geometry in hexafluoroisopropanol (HFIP) but, for unhindered cases, with inversion of geometry in DMSO. When an acyloxy substituent is positioned to participate in the reactio

Full text of DOI:10.1016/j.tetlet.2010.11.001

Tetrahedron Letters 52 (2011) 2115–2116
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Tetrahedron Letters
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Iodoolefinic polypropionate building blocks from vinyl silanes with control
of geometry by solvent and by neighboring group participation
⇑
Kathlyn A. Parker , Richard W. Denton
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 5 November 2010
Iododesilylation of trisubstituted (Z)-silyl olefins proceeds with retention of geometry in hexafluoroiso-
propanol (HFIP) but, for unhindered cases, with inversion of geometry in DMSO. When an acyloxy sub-
stituent is positioned to participate in the reaction, the protocol consistently leads to inversion of
geometry.
Dedicate this communication to Professor
Harry Wasserman on the occasion of his
90th birthday.
Ó 2010 Published by Elsevier Ltd.
Keywords:
Vinyl iodide
Solvent effect
Anchimeric assistance
Polypropionate
Iododesilylation
Vinyl iodides with defined geometry are important chemical
intermediates.1 Their preparation from vinyl silanes with retention
of geometry by use of acetonitrile/trichloroacetonitrile2 or hexa-
fluoroisopropanol (HFIP)3 as solvent is an attractive synthetic
method. We recently took advantage of this transformation in
order to convert trisubstituted (Z)-vinyl silane (Z)-1 (R = TBS,
R0 = MOM) into the corresponding vinyl iodide (Z)-2 (R = TBS,
R0 = MOM, Scheme 1); we viewed this iodide as a useful building
block for polypropionates in which there is a (Z)-trisubstituted
olefin.4
During the course of our studies, we noted that iododesilylation
in some solvent systems gave appreciable amounts of vinyl iodides
in which the geometry of the double bond had not been
retained.2,3,5 Therefore, we imagined that we might find conditions
that would lead from the now readily accessible, protected homo-
allylic alcohol substrates (Z)-1,4 to trisubstituted vinyl iodides
(E)-2 with complete inversion of the geometry of the double bond
(Scheme 1).6,7 A syn, anti (E)-isomer of iodide 2 is considered a
building block for khafrefungin (3)8 and the anti, anti (E)-isomer
is a potential building block for tirandamycin A (4,9 see Fig. 1).
We first examined the chemistry of interest in the model homo-
allylic system (Z)-5. Iododesilylation of (Z)-5a–d10 with NIS was
studied in three solvent media (Table 1). As expected on the basis
of our earlier work,4 alcohol (Z)-5a,11 when treated with NIS in
HFIP containing lutidine, gave a mixture of products that contained
only a small amount of the expected (Z)-vinyl iodide. On the other
hand, iododesilylation of substrates (Z)-5b and (Z)-5c in HFIP with
lutidine gave good yields of vinyl iodides (Z)-6b and (Z)-6c,10
respectively, as the almost exclusive products. These results are
consistent with the known propensity of HFIP to favor iododesily-
lation with high levels of retention of geometry. However, reaction
of acetate (Z)-5d gave a 5:95 mixture of (Z)- and (E)-vinyl iodides
(Z)-6d and (E)-6d.10 This example suggests that the homoallylic es-
ter substituent participates in the reaction, adding to the iodonium
ion and then eliminating anti to the TMS group to provide the
product with (E)-geometry.12 This pathway is not entirely surpris-
ing;2,3 however, the high level of inverted geometry is impressive
and clearly useful.
Me3Si
R'O
I
CH3
NIS
CH3
R'O
RO
RO
HFIP
CH3
CH3
CH3
CH3
(Z)-2
(Z)-1
conditions?
RO
CH3
R'O
I
CH3
CH3
(E)-2
⇑
Corresponding author. Tel.: +1 631 632 7851; fax: +1 631 632 7960.
E-mail address: kparker@notes.cc.sunysb.edu (K.A. Parker).
Scheme 1. Established and postulated iododesilylation of polypropionate building
block (Z)-1.
0040-4039/$ - see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2010.11.001

2116
K. A. Parker, R. W. Denton / Tetrahedron Letters 52 (2011) 2115–2116
CH3 CH3 CH3 CH3 CH3 CH3
CH3
Me3Si
MOMO
CH3
NIS
DMSO
O
CO2H
CH3(CH2)9
OH
O
O
O
OH
TBSO
3
HO
CH3
CH3
I
O
(Z )-1a
CH3
I
CH3
MOMO
MOMO
O
OH
O
O
CH3
CH3
+
O
CH3
TBSO
TBSO
H
NH
CH3 CH3
(E)-2a
CH3
CH3
H
CH3
4
(Z)-2a
96% (71:29)
Figure 1. The structures of khafrefungin (3) and tirandamycin A (4).
Scheme 2.
Table 1
Yields and stereoselectivity in iododesilylation of vinyl silanes 5 as a function of
solvent
Me3Si
AcO
CH3
AcO
CH3
NIS
I
n-C5H11
OR
Me3Si
OR
C5H11-n
NIS
C5H11-n
+
I
I
TBSO
TBSO
OR
HFIP,
76%
CH3
CH3
CH3
CH3
(Z)-1b
(E)-2b
Scheme 3.
(Z)-5
(Z)-6
(E)-6
verted (E)-geometry in both the simple, unhindered series 5 (i.e.,
with substrate (Z)-5d) and in the case of polypropionate substrate
(Z)-1b.
Substrate 5
Yield (ratio of (Z)-6 to (E)-6)c Rxn time (h)
HFIP
MeCN/ClCH2CN (4:1)
DMSO
a (R = H)
(ꢀ)a
82% (86:14)b
85% (15:85)d
1.5
18
67
Acknowledgment
b (R = TBS)
c (R = MOM)
d (R = Ac)
72% (97:3)
0.5
53% (72:28)
2
94% (4:96)
117
This work was supported by the Army Breast Cancer Initiative
(BC 051816), the National Institutes of Health (GM 74776), and
the National Science Foundation (CHE-0131146, NMR
instrumentation).
75% (97:3)
0.5
87% (82:18)
19
86% (3:97)
6
94% (5:95)
0.5
48% (7:93)
17
43% (E)-6 only
18
a
b
c
See Ref. 4.
Solvent was neat MeCN.
Determined by integration of the NMR spectrum of the isolated vinyl iodide
References and notes
mixture.
1. Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4442.
2. Stamos, D. P.; Taylor, A. G.; Kishi, Y. Tetrahedron Lett. 1996, 37, 8647.
3. Ilardi, E. A.; Stivala, C. E.; Zakarian, A. Org. Lett. 2008, 10, 1727–1730.
4. Xie, Q.; Denton, R. W.; Parker, K. A. Org. Lett. 2008, 10, 5345–5348.
5. As part of an extensive study of solvent effects on the stereoselectivity of the
halodesilylation of (E)-1-silyloctenes, Tamao had shown that NBS in DMF gave
1-bromooctenes with a high inversion: retention (Z:E) ratio; see: Tamao, K.;
Akita, M.; Maeda, K.; Kumada, M. J. Org. Chem. 1987, 52, 1100.
6. Complex intermediates that contain trisubstituted (E)-olefins adjacent to a
series of asymmetric centers are most often prepared from methyl acetylenes
by hydrozirconation/iodination or hydrostannylation/iodination; see: (a) Hart,
D. W.; Blackburn, T. F.; Schwartz, J. J. Am. Chem. Soc. 1975, 97, 679; (b) Benechie,
M.; Skrydstrup, T.; Khuong-Huu, F. Tetrahedron Lett. 1991, 32, 7535. They have
also been prepared from (E)-vinyl silanes by iododesilyation with retention of
geometry (our Refs. 2–4).
7. During the course of our work, Oguri and co-workers reported complete
inversion of geometry in the iododesilylation of a (Z)-trisubstituted olefin,
unsubstituted on the carbon chain, in DMF; see: Migita, A.; Shichijo, Y.; Oguri,
H. i.; Watanabe, M.; Tokiwano, T.; Oikawa, H. Tetrahedron Lett. 2008, 49, 1021.
8. For total syntheses and biological activities of khafrefungin and its isomers,
see: Shirokawa, S.; Shinoyama, M.; Ooi, I.; Hosokawa, S.; Nakazaki, A.;
Kobayashi, S. Org. Lett. 2007, 9, 849. and references therein.
9. For leading references on tirandamycins A and B, see: Shiratani, T.; Kimura, K.;
Yoshihara, K.; Hatakeyama, S.; Irie, H.; Miyashita, M. Chem. Commun. 1996, 21.
10. Each of these compounds was fully characterized.
d
Yield based on 33% recovered starting material.
In a 4:1 mixture of MeCN/ClCH2CN, iododesilylation of (Z)-5a–c
gave product mixtures in which the (Z)-olefins predominated.
Homoallylic acetate (Z)-5d, under these conditions, again gave al-
most exclusively the (E)-olefin.
Remarkably, reaction of silanes (Z)-5a–c as well as that of silane
(Z)-5d in DMSO supplied almost entirely the inverted E-iodoolefi-
nic products.10 These results are consistent with the general prin-
ciples put forth by Tamao5 for the halodesilylation of disubstituted
vinyl silanes. They implicate a high level of participation by solvent
or, in the case of (Z)-5d, by a nearby participating functional group.
Extension of the solvent-induced inversion of double bond
geometry to more complex substrates was partially successful.
Application of the DMSO protocol to substrate (Z)-1a afforded a
disappointing 71:29 ratio of the known (Z)-2a and the desired
(E)-2a (Scheme 2). The appearance of a significant amount of the
retention product is consistent with increased steric hindrance at
the allylic position2 in substrate (Z)-1a relative to that in the model
system.
11. Alcohol 5a was prepared in three steps from 1-cyclohexyl-3-nonyn-1-ol.
Functionalization with tetramethyldisilazane (TMDS) and intramolecular
On the other hand, treatment of the acetate (Z)-1b10,13 with NIS
(in HFIP with 2,6-lutidine) gave only vinyl iodide (E)-2b10 (Scheme
3) in 76% yield after 1 h at room temperature.
In summary, both unhindered and chain-substituted (Z)-vinyl
silanes ((Z)-5 and (Z)-1a, respectively) give (Z)-vinyl iodides under
the HFIP conditions; however, only the unhindered compounds
were efficiently converted into (E)-vinyl iodides in DMSO. On the
other hand, a well-positioned participating group led to the in-
hydrosilyation
catalyzed
by
the
cationic
ruthenium
complex,
*
[Cp Ru(MeCN)3]PF6 gave the dihydrooxasiline. Ring cleavage with
methyllithium yielded hydroxy vinyl silane 5a. See: (a) Trost, B. M.; Ball, Z.
T. J. Am. Chem. Soc. 2003, 125, 30; (b) Mbaye, M. D.; Demerseman, B.; Renaud, J.-
L.; Toupet, L.; Bruneau, C. Adv. Synth. Catal. 2004, 346, 835.
12. For additional evidence for this mechanism, see Refs. 2 and 3.
13. Acetate (Z)-1b was prepared by 9-BBN hydroboration of our siloxine precursor
(Ref. 4), ring opening with methyllithium, selective protection of the primary
hydroxyl group with TBSCl, and acetylation of the remaining secondary
hydroxyl group.