Preparation of 2-(trimethylsilyl)methyl-2-propen-1-ol derivatives by cobalt catalyzed sp2-sp3 coupling

Article abstract of DOI:10.1016/j.tetlet.2018.06.018

A practical, operationally simple preparation of 2-(trimethylsilyl)methyl-2-propen-1-ol derivatives is described. The cobalt catalyzed coupling of a protected vinyl halide with trimethylsilylmethylmagnesium chloride shows excellent functional group tolerance and provides these synthetically useful allyl silanes in good overall yield. By this method, the use of highly concentrated organolithium reagents, complex reaction protocols, and expensive starting materials is avoided.

Full text of DOI:10.1016/j.tetlet.2018.06.018

Accepted Manuscript
Preparation of 2-(trimethylsilyl)methyl-2-propen-1-ol derivatives by cobalt cat-
alyzed sp2-sp3 coupling
M. Tariq Riaz, Ivanna Pohorilets, Jackson J. Hernandez, Jeovanna Rios, Nancy
I. Totah
PII:
S0040-4039(18)30757-3
https://doi.org/10.1016/j.tetlet.2018.06.018
TETL 50056
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Accepted Date:
7 May 2018
5 June 2018
Please cite this article as: Riaz, M.T., Pohorilets, I., Hernandez, J.J., Rios, J., Totah, N.I., Preparation of 2-
(trimethylsilyl)methyl-2-propen-1-ol derivatives by cobalt catalyzed sp2-sp3 coupling, Tetrahedron Letters (2018),
doi: https://doi.org/10.1016/j.tetlet.2018.06.018
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Preparation of 2-(trimethylsilyl)methyl-2-propen-1-ol derivatives by cobalt
catalyzed sp2-sp3 coupling.
M. Tariq Riaz, Ivanna Pohorilets, Jackson J. Hernandez, Jeovanna Rios, and Nancy I. Totah 1
Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA
Keywords
trimethylenemethane precursors
allylsilane
sp2-sp3 coupling
Co catalyst
Corresponding author. Tel.: +1-315-443-2657; fax: +1-315-443-4070; e-mail:
ntotah@syr.edu
ABSTRACT
A practical, operationally simple preparation of 2-(trimethylsilyl)methyl-2-propen-1-ol derivatives is described. The cobalt catalyzed coupling of a
protected vinyl halide with trimethylsilylmethylmagnesium chloride shows excellent functional group tolerance and provides these synthetically useful
allyl silanes in good overall yield. By this method, the use of highly concentrated organolithium reagents, complex reaction protocols, and expensive
starting materials is avoided.
Introduction
Protected 2-(trimethylsilyl)methyl-2-propen-1-ols 1 have found widespread application in organic synthesis. These versatile reagents
are able to function as nucleophiles, [1] as electrophiles[2] (depending of the on the nature of the oxygen protecting group), and as all-
carbon 1,3-dipole equivalents in transition metal catalyzed processes.[3] As such, these compounds participate in 1,2- and 1,4-addition
reactions,[4] ene reactions,[5] C-glycosylation[6] and Ferrier-type processes,[7] and oxidative radical additions,[8] to name a few.
Compounds 1 in which the oxygen atom bears an ester functionality are particularly useful in ring forming reactions. Such processes
include [3+2] cycloadditions for the preparation of cyclopentanes (2, 3),[9] dihydrofurans (4),[10] and pyrrolidines (5),[11] [3+3]
cycloadditions for the preparation of piperidines (6)[12] and other heterocycles (7)[13] and [3+4] cycloadditions for the preparation of
fused seven-membered carbocyclic ring systems (8).[14] The preparation of bridged 9-membered carbocycles (9) by [3+6] cycloaddition
reactions with tropones is also known.[15] Examples shown in Scheme 1 are representative. Reagents of these types (1) have also found
application in the preparation of natural products and other complex molecular frameworks.[16]
The synthesis of these reagents 1 is typically achieved by manipulation of the corresponding alcohol, itself prepared in two steps from
2-methyl-2-propen-1-ol through the intermediacy of the corresponding dianion.[17] Though direct, this process is technically demanding,
and requires the use of highly concentrated n-butyllithium and carefully controlled reaction conditions. Over the years a number of other
protocols have been reported for the synthesis of 2-(trimethylsilyl)methyl-2-propen-1-ol, but these preparations often require the use of
specially prepared reagents, labyrinthine reaction protocols, and superfluous protection and/or deprotection steps.[18] In most cases, the
requisite starting material is also quite expensive.

Scheme 1.
Results and discussion
Our interest in the development of tandem reaction processes using functionalized allylsilanes led us to consider an alternative
preparation of protected 2-(trimethylsilyl)methyl-2-propen-1-ols 1 that was operationally simple and made use of relatively inexpensive
starting materials. Toward this end, we anticipated that the desired substrates would be accessible through a cobalt catalyzed sp2-sp3
coupling reaction between trimethylsilyl-methylmagnesium chloride[19] and a functionalized vinyl halide 10 in which a variety of
protected alcohols are available by manipulation of 2-iodo-2-propen-1-ol 11 (Scheme 2). This latter is readily available on large scale
from inexpensive propargyl alcohol.[20] This strategy differs from prior methods of preparation in that functionalization of the hydroxyl
group occurs prior to C-C bond formation and thus avoids superfluous protecting group manipulations.
Scheme 2.
In the forward sense, the requisite vinyl iodide was readily prepared by the method of NicolaouError! Bookmark not defined. whereby addition
of the alkyne to a mixture of NaI and TMSCl in wet acetonitrile provided the desired product 11 as a single regioisomer in 60% yield.
Purification can be effected by either column chromatography or vacuum distillation, depending on reaction scale. This product can be
stored over copper wire in the freezer for several months without significant decomposition.
With the vinyl halide 11 in hand, a variety of ethers, esters and carbonates were prepared for evaluation in the cobalt catalyzed coupling
reaction. The choice of protecting groups was influenced by differences in steric bulk, stability to acidic and/or basic reaction conditions,
reactivity toward Grignard reagents, and variation in deprotection regimens. Protecting groups were introduced under standard conditions
to give the desired products in good to excellent yields (Table 1). Attempts to prepare the benzyl ethers 14 and 15 under basic conditions
were unsatisfactory, though the desired compounds could be readily obtained under acidic conditions using the corresponding benzyl-or
p-methyoxybenzyl trichloroacetimidates respectively (entries 3 and 4). Additional details on the preparation of protected vinyl iodides 12-
21 are provided in the experimental section.
Table 1. Protection of Vinyl Iodide 11.
vinyl iodide
yield
72%
entry
1
12
2
3
4
83%
98%
63%
13
14
15

5
83%
82%
85%
85%
76%
98%
16
17
18
19
20
21
6
7
8
9
10
These protected vinyl halides were then subjected to the cobalt-catalyzed cross coupling reaction with trimethylsilylmethyl-
magnesium chloride (Table 2).[21] Initial experiments focused on the use of substrates in which the alcohol 11 was protected as an ether
functionality. Both TBS 12 and TBDPS 13 ethers performed well in this transformation providing the coupled products 22 and 23 in 74
and 81% yields respectively (entries 1 and 2). Benzyl 14 and p-methoxybenzyl 15 ethers (entries 3 and 4) were also compatible with the
reaction conditions, as were acetals with MOM 16 and THP groups 17 (entries 5 and 6). Yields of the corresponding allyl silanes 24-27
ranged from 66-79%.
A more challenging test of this methodology was anticipated to be the use of vinyl halides 1 that contained ester functionality. As the
corresponding allyl silanes are commonly used as precursors to trimethylenemethane metal complexes, we were interested to see if this
method could be utilized for the preparation of substrates of this type. A series of carbonyl compounds 18-21 were thus prepared, and
their compatibility for use with a Grignard coupling partner evaluated. As shown, not only were hindered and less reactive substrates with
pivalate 18 and Boc 21 protecting groups tolerant of the reaction conditions (entries 7 and 10), but benzoate 19 and acetate 20 protected
substrates could be utilized as well (entries 8 and 9). In these cases, yields ranged from 70-76%. Examination of the crude proton NMRs
of the coupling reactions of ester protected substrates showed little if any products resulting from cleavage of the protecting group.
Table 2. Cobalt Catalyzed Coupling Reactions.
entry
1
vinyl iodide
product
yield
74%
12 (R = TBS)
22
23
2
13 (R = TBDPS)
81%
3
4
5
6
7
8
14 (R = Bn)
71%
68%
79%
66%
70%
70%
24
25
26
27
28
29
15 (R = PMB)
16 (R = MOM)
17 (R = THP)
18 (R = Piv)
19 (R = Bz)

9
20 (R = Ac)
21 (R = Boc)
74%
76%
30
31
10
Conclusion
In summary, a practical protocol for the synthesis of protected 2-(trimethylsilyl)methyl-2-propen-1-ols has been developed.
Preparation of these synthetically useful allyl silanes via the cobalt-catalyzed sp2-sp3 coupling reaction of a protected 2-iodo-2-propen-1-
ol 11 and (trimethylsilylmethyl)magnesium chloride provides an attractive alternative to existing methodologies. The sequence is
operationally simple, makes use of inexpensive, readily available starting materials, and is characterized by short reaction times. All
reactions in the sequence proceed at room temperature. Intricate reagent preparations are not required, and the use of concentrated
organolithiums is avoided. Further, the procedure is compatible with a wide variety of functionality, facilitating the direct preparation of
different oxygen derivatives without extraneous protection/deprotection steps.
Acknowledgments
We thank the following organizations for providing fellowship support: ACS Project SEED (JH), National Science Foundation (CHE-
1263154; JR, JH), and the IRSIP of the Higher Education Commission, Pakistan (MTR). In addition, support for the Syracuse University
NMR facility (National Science Foundation, CHE-1229345) is gratefully acknowledged.
Supplementary Material
Supplementary data (experimental procedures, characterization data, copies of 1H and 13C NMR spectra) associated with this article
can be found in the online version at http://xxx.
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Highlights
• Versatile 2-(trimethylsilyl)methyl-2-propen-1-ol derivatives prepared.
• Method shows broad functional group compatability.
• Mild reaction conditions and an operationally simple reaction protocol.
• Target compounds isolated in good overall yield.