the chemistry of carbenes has seen an explosive growth both as complexes for metals and as organocatalysts , but our knowledge of the chemistry of the derived enetetramines is much less advanced .
we have recently shown that unactivated alkyl and aryl halides are reduced by enetetramines , acting as very strong neutral , ground - state , organic electron donors .
thus benzimidazole - based donor 1(4,5 ) was found to react efficiently via set ( single electron transfer ) with unactivated aryl as well as alkyl iodides , e.g. , 3 and 5 , respectively , leading to the cyclization products 4 and 6 derived from the corresponding initial aryl and alkyl radicals ( scheme 1 ) .
substrates such as 5 showed that alkyl carbanions were not intermediates ( carbanion formation would be expected to lead to p - methoxystyrene and cyclohex-2-en-1-ol ) , but these products were not detected .
more recently the imidazole - derived donor , 2 , was shown to be an even more powerful reagent than 1 , featuring double - electron transfer to iodoarenes , leading to cyclization of the aryl anion derived from ester 7 to form ketone 8 and reduced product 9 .
the impressive reducing power of reagents such as 1 and 2(10 ) is ascribed both to the ability of nitrogen atoms to stabilize positive charge on an adjacent carbon , and to the aromatization energy that is gained , following electron donation , on forming their radical - cations 11 and 13 , respectively , and their dications 12 and 14 , respectively .
comparison with the simpler enetetramine , tdae 10 , shows that 10 is a weaker electron donor ; oxidation does not lead to aromatic stabilization energy .
the greater reactivity of 2 , compared to 1 , relates to the greater aromatization energy associated with formation of the bis - imidazolium salt 14 from precursor 2 , compared to forming bis - benzimidazolium salt 12 from precursor 1 .
similar arguments can apply to the radical cations 13 and 11 , as depicted in scheme 2 .
this paper now reports and investigates the unprecedented formation of aliphatic aldehydes by extrusion of a single carbon atom from the imidazolium salt - derived enetetramine 2 when it reacts with alkyl and appropriate aryl halides .
this new reactivity came to light upon reacting alkyl halides with enetetramine 2 ( scheme 3 ) .
donor 2 ( 1.5 equiv ) was prepared in situ by deprotonation of salt 15(7,8 ) and subsequently reacted with 5-phenyliodopentane 16 .
when a neutral workup was used , a trace of aldehyde was noted in the nmr spectra of the crude reaction products . turning to acidic workup afforded aldehyde 17 in 19% yield . to explore whether an aldehyde might be obtained from an alkyl bromide , substrate 18
the conditions of the reaction were then studied to maximize the yield of the aldehyde .
an excess of donor 2 ( 5 equiv , concentrated solution ) led to isolation of aldehyde 19 in 61% yield following acidic workup . again , the yield of the aldehyde was significant only when the reaction workup featured acidic conditions , suggesting that the aldehyde required to be liberated from a protected form during workup . the origin of the aldehyde carbonyl carbon in products 17 and 19 was now addressed .
this could happen by conversion of the alkyl halide to the corresponding alkyl anion following transfer of two electrons from donor 2 . to test this possibility ,
reaction of the corresponding alkyl anion with dma should now afford the ketone , 20 , following workup .
however , no ketone was formed , and , instead , aldehyde 17 was again isolated ( 32% yield ) after further purification by column chromatography .
this clearly shows that the aldehyde product can arise from a pathway that does not involve dmf and hence really must involve the bisimidazolylidene 2 .
this still left the possibility that reaction in dmf as solvent could form aldehyde by two routes , in one of which the aldehyde carbon was derived from 2 , while in the other it derived from dmf .
[ it will be shown later with substrate 47 that aldehyde does not derive from dmf at all , within the limits of detection ] .
looking for mechanistic routes for cc bond formation between the substrate 21 and molecule 2 , three options present themselves , all involving reaction at the central carbons of 2 ( scheme 4 ) .
thus 2 could behave simply as a nucleophile , undergoing sn2 reaction with the alkyl halide substrates .
the driving force for regioselective reaction at the central carbons is the aromaticity of the resulting imidazolium ring in 24 .
an alternative route to the same product features electron transfer from the donor 2 to the alkyl halide 21 .
the third possibility is that an alkyl anion 23 is formed from the substrate following transfer of two electrons as suggested above ; 23 would then be well placed to couple to dication 14 .
the path to 24 will be discussed later in this article , but first a mechanism needs to be proposed to explain how such an intermediate could lead to aldehydes ( scheme 5 ) .
the ultimate fate of the carbene group is not clear from the products that we isolate , but for the formation of the aldehyde , a possible route would feature the reduction of the imidazolium unit of 25 to radical 26 by electron transfer , followed by hydrogen atom abstraction to give the imidazoline 27 .
the best yields of aldehydes were obtained when multiple equivalents of bisimidazolylidene 2 were used in the reaction , and when the reaction featured acidic workup conditions .
the need for multiple equivalents of donor 2 would be consistent with the need for a reduction step ( 25 to 26 ) ; excess of donor 2 would facilitate this electron transfer .
similarly , the improved yields of aldehydes isolated from these reactions when using acidic workup conditions would be explained by the need to hydrolyze imidazoline 27 . alternatively ( we thank a reviewer for this suggestion ) , 25 could undergo deprotonation to form enediamine 29 . the deprotonation might be carried out intramolecularly by the carbene carbon in 25 , which , from a model , might be feasible . within 29 ,
nucleophilic attack by the enediamine upon the imidazolium salt would afford 30 , and hydrolysis of this compound on acidic workup would lead to formation of aldehyde - acid 31 , which could undergo decarboxylation to give the observed aldehydes . to see if evidence in favor of either route could be found , the simple 1,3-dimethyl-2-(3-phenylpropyl)-1h - imidazolium iodide 33 was prepared and treated with donor 2 . in the  reductive route 
if this happens , then other imidazolium salts , such as 33 , should also be reduced by 2 .
however , no aldehyde was formed in the reaction of iodide 33 with donor 2 , suggesting that aldehydes do not arise from a reductive route . the alternative route to aldehydes 28 goes through hydrolysis of imidazolium salt 30 during the workup procedure .
if that imidazolium salt can be hydrolyzed to an acid , then imidazolium salt 33 should also afford an acid , i.e. , 35 .
the reaction of imidazolium salt 33 with 2 , followed by acidic workup did indeed afford acid 35 but in low yield ( 2% ) .
compound 30 is relatively more activated than 33 for hydrolysis , and so it is possible that it would afford higher yields of acid 31 ( and subsequently aldehyde 28 ) than seen here for acid 35 .
thus , the best working hypothesis is that the aldehydes 28 arise from the hydrolysis and decarboxylation route .
the favored route to aldehydes discussed above , relies on iminium saltenediamine conversions between 25 , 29 , and 30 .
we envisaged that 37 , an analogue of 25 , featuring a leaving group ( or )  to the imidazolium salt would lead to further reactions that would signal its role as an intermediate ( see scheme 6 ) .
deprotonation of 37 would afford the enediamine 38 ; this compound would then be primed to expel the alkoxide group ro , thereby affording imidazolium cation 39 . in turn , this could be deprotonated in the basic medium to yield 40 , from which expulsion of ro could be expected .
the isolation of alcohol(s ) roh , roh could therefore be an important pointer in support of alkylimidazolium intermediates , such as 25 in scheme 5 . while alcohol roh could also arise through other mechanisms , it is difficult to think of an alternative way in which roh would be produced , and hence we set particular importance on the isolation of this alcohol in the test reactions below .
the hindered alkyl halide substrates 45ah were selected and prepared as shown in scheme 7 .
reaction of initial substrate 45a very clearly led to mixtures of the corresponding two alcohols , phenylpropanol + benzyl alcohol ( 1.5:1 ) .
sensing that the deviation from an expected 1:1 ratio might be due to volatility of the benzyl alcohol , substrate 45b was reacted with 2 and afforded a 1:1 mixture of phenylpropanol + phenylbutanol as judged by nmr , in accordance with the hypothesis in scheme 6 . however , the separation of the alcohols was challenging on the scale of the experiment , and so 45ch employed r = me to facilitate isolation of roh .
clearly , the alcohol roh is isolated in high yield from these reactions , completely consistent with scheme 6 .
the aliphatic substrates 16 and 18 do not allow us to distinguish between the three routes shown in scheme 4 .
on the other hand , reactions of donor 2 with substrates 45 do provide key information .
the outcomes of these reactions are consistent with both the direct sn2 mechanism and/or with the intermediacy of aliphatic radicals from set to the alkyl halides .
however , they are inconsistent with formation of alkyl anions , since the developing carbanion represented by 46 should force the -elimination of the alkoxide in a concerted reaction affording 44 , but no 44 was formed . to gain further insight ,
iodide 47 afforded two products , 48 and 49 , in 42% and 13% yields , respectively ( see scheme 8) .
the same products 48 ( 42% ) and aldehyde 49 ( 5% ) were afforded .
the aldehyde showed no labeling with deuterium in nmr or mass spectrometry this supports our previous statement that the aldehyde products do not incorporate the formyl group of dmf ] .
similarly , iodide 50 gave reduced product 51 ( 40% ) and aldehyde 52 ( 5% ) .
for both reactions , the major product is likely to arise from transfer of two electrons to the substrate to form the aryl anion , consistent with our previous results for donor 2 . as in the experiments with the previous substrates in this article , isolation of aldehyde was dependent on the use of acid in the reaction workup .
the two aldehydes 49 and 52 , as minor products , can not arise from sn2 reaction and so must result from the trapping of an alkyl radical or an alkyl anion .
although the formation of alkyl anions by direct reduction of alkyl halides ( via alkyl radicals ) is rejected above following the experiments with substrates 45 , alkyl anions might arise indirectly by cyclization of aryl anions , and aryl anions are known to form when donor 2 reacts with aryl iodides . to probe that point , substrate 53 was prepared and reacted with donor 2 in dmf ( scheme 9 ) .
this afforded three products in a combined yield of 70% : the  reduced product 54 ( 27% ) , the cyclized product 55 ( 8% ) and the alcohol 56 ( 35% ) ( scheme 9 ) .
formation of product 54 sees two electrons being transferred in quick succession from donor 2 to substrate 53(8 ) to form anion 58 ( scheme 10 ) .
if anion 58 could cyclize to give aliphatic anion 62 , this would lead to formation of alcohol 56 as well as vinylindoline 63 .
alcohol 56 arises through initial and rapid cyclization of aryl radical 57 to form 59 ( scheme 10 ) .
hydrogen abstraction by 59 then leads to 55 . alternatively , trapping of 59 with radical - cation 13 affords salt 60 , which acts as the source of alcohol 56 following the pathway proposed in scheme 6 .
no products that derived from the electrophile 61 were detected , signaling its high reactivity . in summary ,
aliphatic aldehydes are formed on reaction of bisimidazolylidene 2 with both aliphatic and aryl iodides as well as alkyl bromides .
an sn2 mechanism may play a role in aldehyde formation from the aliphatic substrates , but the aldehydes formed from the aryl substrates arise via a radical mechanism .
this indicates that some aryl radicals cyclize before a second electron can be received from donor 2 .
 reaction of imidazolylidene - derived enetetramine 2 with aliphatic iodides and bromides ( and with aryl iodides bearing alkene - containing side - chains in the ortho - position ) leads to formation of aliphatic aldehydes through an unprecedented extrusion of a one - carbon unit from the enetetramine . 
 an intermediate 2-alkylimidazoline 24 is proposed , where the alkyl group derives from the substrate ; this imidazoline undergoes further reaction in situ to afford the observed aldehydes on acidic workup . 
 modified substrates were designed and prepared to probe the chemistry of the alkylimidazoline adducts and provided extensive information on the chemistry of the adducts . 
Introduction
Results and Discussion