Elimination vs. substitution in the reaction of 3-stannyl esters and 3-stannyl nitriles with sodium tert -butoxide in DMSO

The reaction of 3-stannyl propanoates and 3-stannyl propanonitriles with sodium tert -butoxide in DMSO leads to elimination and/or substitution products. The composition of the product mixture depends on the nature of the ligands attached to tin and also on the nature of the functional group (COOMe or CN). Stereochemical results suggest that the elimination reactions proceed through an (E1cB) R mechanism.


Introduction
In previous investigations 1 we have reported that the reaction of a series of threo-3-(triorganostannyl)nitriles with sodium tert-butoxide in t-BuOH led to Z/E mixtures of α-methylene nitriles in different yields under appropriate conditions.
Recently 2 we have found that a series of 3-(triorganostannyl)ketones, under similar conditions, afforded elimination and/or substitution products.The elimination reaction exhibited features characteristic of a (E1cB) R mechanism.Our results indicated that the elimination/substitution ratios obtained were dependent upon the nature of the ligands attached to the tin atom.Thus, while substrates containing better nucleofuges such as Cl 3 Sn, Ph 2 BrSn and Ph 3 Sn led exclusively to elimination products, substrates supporting a poor nucleofuge such as Me 3 Sn led to a mixture of elimination/substitution products or to exclusively substitution products which are dependent on the temperature.We have also found that a phenyl group attached to C-2, due to stabilization of the intermediate anion, increased the elimination/substitution ratio in a substrate that contained a poor nucleofuge such as Me 3 Sn.
A change from t-BuOH to dimethyl sulfoxide (DMSO) caused a very dramatic acceleration of either the elimination or substitution reactions.Under these conditions there were exclusive reactions depending only on the nature of the ligands attached to tin.
Taking into account our results we considered that it would be of interest to investigate the reactivity of comparable 3-(triorganostannyl)nitriles and 3-(triorganostannyl)esters under similar conditions.These reactions could be of interest not only from a mechanistic point of view but also as a synthetic tool.We wish to report the results obtained in the reaction of a series of methyl 3-(triorganostannyl)propanoates and 3-(triorganostannyl)propanonitriles with sodium tert-butoxide in DMSO.

Results and Discussion
The reactions were carried out with substrates supporting two chiral centres because we could ascertain at the same time the course and stereochemistry of the reaction by using individual diastereomers as starting material and determining isomeric compositions of the products.
The results obtained indicate that in the studied reactions the stannyl group can depart in a nucleofugal sense as well as an electrofugal sense, leading to elimination or substitution products, respectively.
The results obtained indicate that the tert-butoxide anion reacts with these substrates in a similar way as with 3-stannyl ketones. 2 The hydrodestannylated products obtained could be explained as the result of a nucleophilic attack of the tert-butoxide anion at the tin atom. 4It should be noted that high yields of acids are formed in the reactions carried out with tributyltin derivatives 8 and 9. Probably, the tin oxide generated in the reaction accelerates the hydrolysis of the ester group leading to high yields of the corresponding acids in very short times. 5n the other hand, the formation of olefins should be due to an elimination reaction where the tert-butoxide anion acts as a base abstracting the proton from C-2 and the organotin anion acts as a nucleofuge.The stereochemical results summarized in Table 1 show that there is complete stereoconvergence in the elimination reaction leading always to the olefin E, independently of the starting substrate configuration.It should be mentioned that threo esters always led to lower olefin yields than their erythro isomers in the same reaction time.When these reactions were quenched at shorter times (5 min) it was observed that olefins E were formed together with a mixture of isomeric starting material.All these observations support an (E1cB) R mechanism as represented in Scheme 1.The stereoselectivity of the elimination reaction implies that conformation A is preferred instead of B. On these grounds it may be assumed that for these compounds the interaction between 3-Ph and COOMe is energetically less favourable than that between Me/Ph and Ph/Ph, in spite of their A-values. 6These stereochemical results agreed with those reported by Cabaleiro, 7  As shown in Scheme 2, the observed product distribution is strongly dependent on the nature of the ligands attached to the tin atom.Meanwhile 3-(triphenyl) and 3-(dibutylchlorostannyl)esters 1, 4, 14 and 15 led, exclusively, to olefins, 3-(trimethyl) and 3-(tributylstannyl)esters 7, 8 and 9 afforded only substitution products.Changes in the substituent on C-2 have no detectable effect on the product mixtures.
We assumed that with 3-stannyl nitriles as substrates, the substitution reaction is probably preferred over the elimination reaction because the elimination mechanism is slowed by the less acidic character of the hydrogen on C-2.

Scheme 3
Although similar stereochemical results were obtained with the erythro nitriles, they always led to lower olefin yields than their threo isomers.The diastereoselectivity of the elimination reaction could be explained on the basis of the stability of the carbanion intermediate.Considering steric effects 6 the lowest energy conformation should be conformation C (Scheme 4).

Scheme 4
In summary, the results obtained from the present study confirm that the stannyl group in 3stannyl esters and in 3-stannyl nitriles as well as in 3-stannyl ketones can be electrofugal or nucleofugal in favorable circumstances.We found that all the substrates studied led exclusively to the corresponding substitution product when a trialkylstannyl group (Me 3 Sn, Bu 3 Sn) is attached to C-3.On the other hand, the elimination reaction is exclusive with 3-stannyl esters and 3-stannyl ketones 2 containing good nucleofuges (Ph 3 Sn, Bu 2 ClSn, Ph 2 BrSn, Cl 3 Sn) but not with comparable 3-stannyl nitriles.The latter substrates, even at higher temperatures, always led to mixtures of elimination/substitution products.
These reactions would have a potential synthetic utility.For example, the reaction of methyl (E)-3-phenyl propenoate (22) with triphenyl-or tributylstannyl lithium in THF and quenching the intermediate carbanions with methyl iodide led to the corresponding adducts 4 and 9 in 85% and 65% yield, respectively. 9The reaction of 4 and 9 with sodium tert-butoxide in DMSO led to eliminations product 6 and to substitution product 12 in high yields, respectively (Table 1, entries 5 and 8).Thus, it is possible, through a simple two step synthesis, to obtain compounds 6 and 12 from ester 22 as is shown in Scheme 5.
Further work is in progress to study the scope of these reactions.Experimental Section General Procedures.The reactions were performed under nitrogen or argon.DMSO was dried under standard methods.Sodium tert-butoxide was sublimated periodically and kept under argon atmosphere.3-Stannyl esters and 3-stannyl nitriles were synthesized according to previously reported procedures. 10The reactions were monitored by TLC, and quantified by GC and on isolated pure product.The measurements were carried out with either a 10% SE-30 (Chrom W 60/80, 6 ft x 1/8 in., SS) or a 3% SE-30 (Chrom W 60/80, 3 ft x 1/8 in., SS) column.
The reactions were performed following the same procedure in all cases.One experiment is described in detail to illustrate the method used.

Reaction of methyl erythro-2,3-diphenyl-3-(triphenylstannyl)propenoate (1) with Na t-BuO in DMSO.
The reaction was carried out in a two-necked, 10 mL, round bottom flask equipped with a nitrogen (argon) inlet, a magnetic stirrer and septums.To a solution of 46.0 mg (0.482 mmol) of Nat-BuO in 2.8 mL of DMSO was added, by syringe, a solution of 1 (211 mg, 0.402 mmol) in 2.8 mL of DMSO.After keeping the reaction mixture under stirring for 15 min at room temperature it was quenched by adding water and extracted with ether (phase 1).The aqueous alkaline phase was acidified and extracted with ether (phase 2).The ester 2, extracted from phase 1, was quantified by GC using the external standard method.The acid 3, extracted from phase 2 was quantified by weighting.Both products were compared with authentic samples prepared by known procedures.

Table 1 .
Reaction of erythro-3-stannyl esters with sodium tert-butoxide in DMSO a a Substrate/base 1/1.1, r.t.b Ester and acid yields between brackets.c Threo isomers led to lower yields.d Threo isomers led to similar yields.e Together with 17% of 13.