In order to carry out the allylation procedures, a suitable acrylate had to be prepared, and since the acrylate 12 had been used successfully in the reported^ allylation reaction with triphenylphosphine [eqn. (5)], it was again used as a substrate in these radical- chain reactions.
çOzEt ÇOzEt
SAd-l
Peroxide initiator
The acrylate 12 was prepared from ethyl l,3-dibromopropane-2-carboxylate (which contained some of the monodehydrobrominated ester) and 1-adamantanethiol [eqn. (6)]/ using a modification of the procedure as described by Barton and Crich.^
1-AdSH + KoCO lO.Et Br— V
^ C 0 2 E t
R r — / Absolute ethanol SAd-l
The first attempted allylation reaction to be carried out, involved the use of a trialkylborane to convert the electrophilic thiyl radical into a nucleophilic alkyl radical [eqn. (1), Scheme 2],^ which can then go on to add to the acrylate 12.
When a mixture of 12 (2.5 mmol), trihexylborane (2.8 mmol) and TBHN (5 mol%) was stirred in benzene (5 cm^) at 60 °C for 2 h under argon, with subsequent removal of the solvent under reduced pressure only a trace of product 14^ was formed, as judged by NMR spectroscopic analysis of the crude reaction mixture. Although only a trace of starting material was detected by NMR, indicating that a reaction had taken place, the main product appeared to be a polymer, since broad peaks at 3 - 4 ppm and 1 - 2 ppm dominated the spectrum.
COoEt SAd-l
TBHN, benzene, 60 °C, 2 h
It is possible that although the product is formed in the reaction, subsequent addition to the terminal double bond in the product 14 of the thiyl or hexyl radical may occur, leading ultimately to polymer formation. The starting material 12 may be involved in competing polymerisation.
To limit the amount of polymer formed, various changes to the above experimental conditions were made and the details of the radical reactions of the acrylate 12 with trialkylboranes are listed in Table 1, The same molar quantities of trialkylborane and acrylate 12 were always used and, depending on the initiator and the temperature of the reaction, either one addition of initiator was made at the beginning of the reaction, or three additions of initiator were made (one at the start of the reaction, and two further additions every 40 minutes). The volume of the solvent used was always the same (5 cm^) and, unless otherwise stated, the quantity of initiator used in the reactions was 5 mol%.
Table 1: Experimental details of the radical reactions of the acrylate 12 with various trialkylboranes
Experiment No.
Trialkylborane Initiator Solvent Time Temp.
(1) Trihexylborane TBHN (one addition) Benzene 3 h 60 °C (2) Trihexylborane DBPC (15) (three additions) Octane 3 h 115 °C (3) T rii sobutylborane TBHN (one addition) Benzene 3 h 60 °C
(4) Triisobutylborane AIBN (10 mol%) (one addition)
Benzene 2 h At reflux
With both experiments (1) and (2), polymer was the main product of reaction (as judged by *H NMR spectroscopic analysis of the crude reaction product) and no
substantial amount of acrylate 14 could be detected.
When triisobutylborane was used in the reaction, the expected product would be the acrylate 16. However, as judged by NMR spectroscopic analysis of the crude product from experiments (3) and (4), no 16 had been formed and again a polymer was the main product of reaction.
B u'O O ^^O O B u' !OiEt
SAd-l
With all of these reactions, the polymer produced was not isolated or characterised and as the reactions of the acrylate 12 with trialkylboranes did not yield any of the desired product acrylates, it was thought necessary to investigate other sources of carbon-centred radicals for the proposed allylation procedure.
Another process that converts the electrophilic thiyl radical into a nucleophilic carbon-centred radical is its reaction with an aldehyde to give an acyl radical [eqn. (2), Scheme 2].^
COoEt COzEt
1-AdS
When a mixture of the acrylate 12 (2.5 mmol), butanal (7.5 mmol) and TBHN (5 mol%) was stirred in benzene (5 cm^) at 60 °C for 3 h under argon, no product 17 could be detected in the crude mixture, as judged by NMR spectroscopy. Again, broad peaks at 3 - 4 ppm and 1 - 2 ppm dominated the spectrum and no significant amount of starting material 12 was seen in the spectrum; this indicates that polymerisation is the main reaction that occurs.
As reaction with aldehydes was not successful, the addition of the thiyl radical to an electron-rich alkene to give the nucleophilic carbon-centred radical adduct [eqn. (3), Scheme 2],^ which can then go on to add to the acrylate 12 to form the p-thioalkyl radical, was investigated. However, when a mixture of the acrylate 12 (2.5 mmol), isopropenyl acetate (2.8 mmol) and AIBN (10 mol%) was stirred in benzene (5 cm^) at reflux for 3 h under argon, no product 18 was formed, and only polymer was detected, as judged by ^H NMR spectroscopic analysis of the crude reaction mixture.
Since these reactions did not yield any of the desired product acrylates, a slightly different conversion process was attempted. As the electrophilic thiyl radical is known to abstract hydrogen from silanes to produce the nucleophilic silyl radical,^ it was hypothesized that this conversion process might be used in the allylation reaction, as shown in Scheme 5. (R = Ph) SR COzEt 1 Scheme 5 12 r ’ = Ad-l
The mechanism involves abstraction of hydrogen from the silane by the thiyl radical to give the nucleophilic silyl radical which then adds to the terminal double bond of the acrylate 1 to form the p-thioalkyl radical, which undergoes p-scission to regenerate the thiyl radical and give the product acrylate 19. When a mixture of the acrylate 12 (1.8 mmol), PhgSiH (2.7 mmol) and TBHN (5 mol%) was stirred in 1,4-dioxane (4 cm^) at 60 °C for 4 h under argon, conversion of 12 to give 20 was ca. 60% complete, as judged by NMR spectroscopic analysis of the crude mixture, and 20 was isolated in 46% yield by flash-column chromatography. However, a substantial amount of polymer and some starting material 12 was also detected in the NMR spectrum and as 20 was only produced in a moderate yield, various changes to the experimental conditions were made in an effort to increase the yield. When a larger quantity of triphenylsilane was used in the reaction (2.5 mol equiv. instead of 1.5 mol equiv.), the amount of product 20
octane as solvent, with three additions of the peroxyketal initiator (DBPC) 15, only a small amount of product 20 was produced. By reducing the temperature to 80 °C, with 1,4-dioxane as solvent and one addition of dilauroyl peroxide (DLP) initiator, no further increase of the product yield of 20 was observed. Therefore, it can be concluded that the original experimental conditions led to the highest yield of the novel product 20. However, as only moderate success was achieved with this allylation procedure using triphenylsilane, and since the various other allylation procedures investigated were not successful, no further time was spent on this part of the project.
4.3.2 Ethyl 3-aIkyIthioacrylates
A variety of known and novel thioacrylates were prepared as substrates for a
projected vinylation procedure, which again would involve a P-thioalkyl radical as a key intermediate (Scheme 3). SH 21 (91%) Cis.Trans = 1:5.5 COÆt COÆt 22 (70%) Cis.Trans = 1.4:1 23 (96%) Cis.Trans = 1.1:1 COoEt SH 24 (93%) Cis.Trans = 4.4:1
The known thioacrylates 22/^ 23^^ and 24^^ were prepared by Michael-type addition of the corresponding thiol to ethyl propiolate in ether, catalysed by
triethylamine/"^ At the beginning of this investigation, the first aim was to test how reactive these acrylates were, and if any product alkene could be formed; therefore it was not considered necessary to use either the pure cis or trans isomer and the starting thioacrylate was used as a mixture of cis and trans isomers. The novel thioacrylates 27 and 28 were prepared similarly^"^ in high yields, and were isolated as a mixture of stereoisomers. 1 -Adamantanethiol 26*^ was prepared in 94% yield from the reduction of isothiouronium bromide 25, which had been prepared in 73% yield from the reaction of 1 -bromoadamantane with thiourea.
SH