Selective one-pot synthesis of Z-iodoallylic iodides from propargyl alcohols

Article abstract of DOI:10.1016/j.tetlet.2006.06.081

A selective one-pot procedure was developed for the production of Z-iodoallylic iodides from the corresponding propargyl alcohols.

Full text of DOI:10.1016/j.tetlet.2006.06.081

Tetrahedron Letters 47 (2006) 5867–5868
Selective one-pot synthesis of Z-iodoallylic iodides from
propargyl alcohols
Govindaswamy Manickam,a Umesh Siddappaa and Yong Lib,*
aSyngene International Pvt. Ltd., 20th KM Hosur Road, Electronics City, Bangalore 560 100, India
bKosan Biosciences Inc., Hayward, CA 94545, USA
Received 7 June 2006; revised 13 June 2006; accepted 14 June 2006
Abstract—A selective one-pot procedure was developed for the production of Z-iodoallylic iodides from the corresponding propargyl
alcohols.
Ó 2006 Elsevier Ltd. All rights reserved.
Iodides are useful building blocks in organic synthesis,
particularly allylic and vinyl iodides. Most synthetically
useful allylic vinyl diiodides are made from propargyl
alcohols via multi-steps sequences1 because direct con-
version leads to mixtures in low yields.2 Here we report
that Z-iodoallylic iodides can be obtained in good yields
from propargyl alcohols in a one pot procedure.
requirement. To our delight, when zinc chloride was
used as a catalyst, the reaction proceeded smoothly
to produce diiodide 1 in high yield (Eq. 1).3 Only a
catalytic amount of zinc chloride (10–15 mol %) and
slight excess of trimethylsilyl iodide (2.2 equiv) were
required. The Z/E ratio of the double bond was greater
than 9/1.
In association with one of our projects, large quantities
of diiodide 1 were required. Although 1 can be prepared
via a three-step, two-pot sequence from propargyl alco-
hol,1a a useful one-pot procedure was preferred. We
envisioned that a Lewis acid catalyzed addition of HI
across the triple bond of 2-butyn-1-ol followed by iodin-
ation of the resulting allylic alcohol would fulfill the
2.2 eq. TMSI
10-15 mol% ZnCl2
OH
ð1Þ
CH2Cl2, -40-0 oC
I
I
1
93% yield, Z/E>9/1
Table 1. Conversion of alkynols to diiodides
Entry
Starting material
Products
Yield (%)
Z/E ratioc
Product ratiod
OH
1
93a
9.2/0.8
I
I
OH
2
3
80b
80b
9/1
I
I
Ph
OH
9.5/0.5
Ph
I
I
I
OH
4
65b
7/3
I
(continued on next page)
*
Corresponding author. Tel.: +1 510 731 5203; fax: +1 510 732 8401; e-mail: li@kosan.com
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.081

5868
G. Manickam et al. / Tetrahedron Letters 47 (2006) 5867–5868
Table 1 (continued)
Entry
Starting material
Products
Yield (%)
Z/E ratioc
Product ratiod
A/B 4.4/5.6
Ph
I
A: 35a
B: 45a
Ph
OH
5
A
I
Ph
I
B
O
I
A: 25b
B: 50b
A
6
7
A/B 3.3/6.7
OH
I
I
B
I
I
A: 62b
1: 19b
A/1 7.5/2.5
A
OH
I
OH
I
I
1
a Purified by vacuum distillation.
b Purified by silica gel chromatography.
c Z/E ratio was determined by 1H NMR of crude reaction mixtures.
d Product ratios are based on purified materials.
H
OH
TMSI
I
I
O
ZnCl2
I
Zn
1
Cl
Scheme 1.
Having succeeded in generating 1 from 2-butyn-1-ol, we
then examined several other alkynyl alcohols to probe
the generality of the reaction (Table 1). Similar results
were observed with ethyl and phenyl substituted propar-
gyl alcohols (entries 2 and 3). Extending the method to
homo-propargyl alcohol led to decreased, but respect-
able, yield and Z/E selectivity (entry 4). Additional dete-
rioration in selectivity was observed as the hydroxyl
group is further removed away from the triple bond
(entry 5). The formation of product B in entry 5 could
occur via cyclization to a dihydropyran intermediate
followed by acid catalyzed ring-opening. The method-
ology cannot be applied to terminal alkynyl alcohols,
since unexpected mixtures were obtained (entries 6 and
7).
iodo-homoallylic iodides from the corresponding alkyn-
yl alcohols.
References and notes
1. (a) Chappell, M. D.; Stachel, S. J.; Lee, C. B.; Danishefsky,
S. J. Org. Lett. 2000, 2, 1633; (b) Kagechika, K.; Ohshima,
T.; Shibasaki, M. Tetrahedron 1993, 49, 1773; (c) Sato, Y.;
Nukui, S.; Sodeoka, M.; Mikiko, S.; Shibasaki, M. Tetra-
hedron 1994, 50, 371.
2. Gras, J.-L.; Chang, K. W.; Bertrand, M. Tetrahedron Lett.
1982, 23, 3571.
3. Trimethylsilyl iodide was purchased from Lancaster Chem-
ical Co. and was used directly. Zinc chloride was purchased
from Aldrich Chemical Co. and fused prior to use.
Experimental procedure: To a solution of 2-butyn-1-ol
(45 g, 0.64 mol) in dry dichloromethane (500 mL) was
added freshly fused zinc chloride (13 g, 0.096 mol) under
nitrogen atmosphere. The reaction mixture was cooled to
ꢀ40 °C, and trimethylsilyl iodide was then introduced
slowly under dark over a period of 30 min. The reaction
mixture was slowly warmed to 0 °C and stirred for 1 h. It
was filtered over a bed of celite and concentrated. The crude
residue was subjected to vacuum distillation to give diiodide
1 as a brown oil (bp 59–62 °C/0.1 mmHg, 184 g, 93%).
Although a mechanistic basis for the role zinc chloride
plays remains to be determined, it is reasonable to
speculate that an iodozincate complex is responsible
for hydroxyl-directed iodide addition to the triple bond
(Scheme 1).
In conclusion, we have developed a simple and econom-
ical procedure for the generation of Z-iodoallylic or Z-