Substituent effects on the reaction of trityl chlorides with Grignard reagents

Article abstract of DOI:10.1016/S0040-4039(00)01470-2

The result of the substitution of trityl chlorides with Grignard reagents was found to be highly dependent on the solvent and the nature of the substituents on the trityl group. In THF, electron donating substituents were found to give high yields of Grig

Full text of DOI:10.1016/S0040-4039(00)01470-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8247–8250
Substituent effects on the reaction of trityl chlorides with
Grignard reagents
Ryan E. Oyler, Benjamin E. Ketz and Timothy E. Glass*
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA
Received 23 August 2000; revised 4 September 2000; accepted 5 September 2000
Abstract
The result of the substitution of trityl chlorides with Grignard reagents was found to be highly
dependent on the solvent and the nature of the substituents on the trityl group. In THF, electron donating
substituents were found to give high yields of Grignard addition while electron withdrawing substituents
were found to give mostly reduction to the corresponding triphenyl methane via hydride abstraction from
the solvent. © 2000 Elsevier Science Ltd. All rights reserved.
As part of an ongoing program geared toward the synthesis of cooperative chemical sensors,1
we required a facile preparation of bis-tritylacetylene compounds bearing a variety of substitu-
tion on the trityl groups. Literature precedent indicated that trityl chlorides could be substituted
with acetylene Grignard reagents in ethereal solvents to give good yields of the tritylacetylene
(Eq. (1)).2,3 Therefore, this class of compounds appeared to be easily accessible.
(1)
Our initial synthetic target required a meta-amino substitution pattern. Thus, the tosyl
protected trityl chloride 3 was treated with acetylene Grignard in THF. However, the only
product obtained was that of reduction (4) with no addition of the Grignard reagent observed
(Eq. (2)). Using benzene as the solvent,4 the trityl acetylene 5 was produced in good yields with
no reduction observed.5 Clearly, THF promoted the reduction and was ultimately the reductant
in the reaction. Further work demonstrated that the reduction process could not always be
avoided. For example, the benzyl protected trityl chloride 6 gave mostly the product of
* Corresponding author. E-mail: teg@chem.psu.edu
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01470-2

8248
reduction (7) with little substitution (<10%) under a variety of conditions (Eq. (3)). Our interest
in this class of compounds prompted an investigation into the substituent effects on the
reduction process involved in Eqs. (2) and (3).
(2)
(3)
Toward this end, four substituted trityl chlorides were treated with excess ethyl Grignard at
two different concentrations in THF (Table 1). In general, electron donating groups tended to
promote Grignard addition while electron withdrawing groups favored the reduction product.
Higher concentration generally gave higher ratios of the Grignard addition product (compare
entries 5 and 6). The sterically imposing tosyl amine groups inhibited Grignard addition to the
extent that only reduction was observed at either concentration (entries 7 and 8). The yields of
compound 8a were better overall than the other substituted trityl chlorides owing to side
reactions which are apparent in the latter cases.
In principle, the mechanism of this reduction could entail a carbocation or a radical
intermediate. The reduction of trityl chlorides with lithium amides has been studied by
Newcomb and proceeds via electron transfer which produces a trityl radical.6 The radical
abstracts a hydrogen atom from the resulting aminyl radical and gives the product of reduction.
However, the results in Table 1 appeared to be more consistent with a pathway in which a trityl
carbocation abstracts a hydride from the solvent.7,8 Indeed, reaction of compound 8a with a
Lewis acid, MgBr2, in THF gives exclusively the reduction product in 70% yield (Eq. (4)). The
reaction was repeated in d8-THF and the product contained >95% deuterium incorporation by
mass spectrometry. Therefore the reduction products presented in Table 1 likely result from
Lewis acid promoted hydride abstraction from THF.
(4)

8249
Table 1a
Entry
1
Trityl chloride
Concentration (M)
0.012
Ratio 9:10
Yield (%)
1:5.0
87
2
3
8a
8b
0.1
0.012
1:4.4
1:1.6
80
51
4
5
0.1
0.012
1:2.9
9.1:1
58
50
6
7
8
8c
3
3
0.1
0.012
0.1
1.1:1
\20:1
\20:1
55
58
45
a All new compounds gave satisfactory spectroscopic analysis.
A simple mechanism consistent with these results is presented in Scheme 1. The magnesium
salts aid in the dissociation of the trityl chloride to the solvent associated trityl cation (11).6,9
This cation then partitions between addition of the Grignard reagent (10) and abstraction of a
hydride from the coordinated solvent (9). Thus, electron withdrawing groups destabilize the
trityl cation making it more reactive and prone to hydride abstraction, while electron donating
groups stabilize the cation which can then be trapped by the Grignard reagent. Increased overall

8250
Scheme 1.
concentration leads to a higher ratio of Grignard addition as this is a bimolecular reaction.
Steric constraints imposed by large substituents disfavor the addition of the Grignard reagent
leading to predominance of the reduction product.
In summary, we have found that the addition of Grignard reagents to trityl chlorides is
dependent on both the solvent and the substituents on the trityl group. Electron donating
groups give higher yields of products which favor Grignard addition while electron withdrawing
groups and sterically demanding groups favor reduction to the triphenyl methane derivative via
hydride abstraction.
Acknowledgements
This work was supported by the National Institutes of Health (GM 59245) and the
Pennsylvania State University TEAS scholars program for undergraduate research.
References
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