Carbonates stannane

This reaction type differs from die three-component reaction reported by Grigg et al. Thus, Grigg et al. [53] (Scheme 7) immobihzed 3-iodo-4-(N-acetyl-N-(2-methyl-2-propenyl)amino)benzoate (36) onto a sohd support. In the presence of suitable Pd salts, Pd substituted the iodide function of the aromatic. The proximal isopropyhdene group trapped the resulting metalated species in an intramolecular Heck reaction. The resulting alkyl palladium species (37) could then react with a suitable carbanion equivalent. The authors used vinylstaimanes or boronates for this purpose, which they obtained in situ from alkynes by hydroboration or hydro-starmylation. The latter procedure allowed them to attach the same vinylic species via its terminal carbon (boronate) (41) and its subterminal carbon (stannane) (39). 

The palladium component may be added to the reaction mixture as Pd(0)- as well as Pd(II)- compound in the latter case the Pd(II)- first has to be reduced to Pd(0)- by excess stannane. Since the first publication on this coupling method by Stille in 1978, this reaction has gained increased importance in synthetic organic chemistry. This is due to the fact that many different types of substrates can be used in this reaction. The following table lists possible carbon electrophiles and stannanes that can be coupled in any combination. 

Tin/lithium exchange on the a-alkoxy stannanes and subsequent addition of carbon dioxide led to optically active (7-protected a-hydroxy acids 18 with retention of configuration and without any loss of stereochemical information11. 

To a solution of 516 nig (1 mmol) of the stannane 17 (R = C.H3, 95% ee) in 10 ml of dry DME is added, at — 78 C, 0.62 nlL of 1.6 M BuLi (1 mmol) in hexane. After 5 min gaseous carbon dioxide is bubbled into ihe yellow solution. The reaction mixture decolorizes immediately. After a further 10 min the reaction is quenched with sat. aq NH4C1. The organic layer is extracted with 2N aq NaOll. Acidification of the aqueous layer with 2N aq IICI is followed by extraction with F.t,o, drying over Na,SC)4 and concentration in vacuo yield 193 mg (92%) 95% ec [determined by HPLC-analysis of the amide obtained by derivati/alion with (S)-x-phenylelhylaminc] [a]20 — 37 (r = 1,6, CI1C1,). 

The readily available organotin compounds include tin hydrides (stannanes) and the corresponding chlorides, with the tri-n-butyl compounds being the most common. Trialkylstannanes can be added to carbon-carbon double and triple bonds. The reaction is usually carried out by a radical chain process,137 and the addition is facilitated by the presence of radical-stabilizing substituents. 

As with the silanes, the most useful synthetic procedures involve electrophilic attack on alkenyl and allylic stannanes. The stannanes are considerably more reactive than the corresponding silanes because there is more anionic character on carbon in the C-Sn bond and it is a weaker bond.156 The most useful reactions in terms of syntheses involve the Lewis acid-catalyzed addition of allylic stannanes to aldehydes.157 The reaction occurs with allylic transposition. 

Enantioselective Addition Reactions of Allylic Stannanes. There have been several studies of the enantiomers of a-oxygenated alkenyl stannanes. The chirality of the a-carbon exerts powerful control on enantioselectivity with the preference for the stannyl group to be anti to the forming bond. This is presumably related to the stereoelectronic effect that facilitates the transfer of electron density from the tin to the forming double bond.182... 

Allylic stannaries with y-oxygen substituents have been used to build up polyoxy-genated carbon chains. For example, 16 reacts with the stannane 17 to give a high preference for the stereoisomer in which the two oxygen substituents are anti. This stereoselectivity is consistent with chelation control.183... 

Lewis acid-mediated ionization of acetals also generates electrophilic carbon intermediates that react readily with allylic stannanes.190 Dithioacetals can be activated by the sulfonium salt [(CH3)2SSCH3]+BF4,191... 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

Scheme 10.17 illustrates allylation by reaction of radical intermediates with allyl stannanes. The first entry uses a carbohydrate-derived xanthate as the radical source. The addition in this case is highly stereoselective because the shape of the bicyclic ring system provides a steric bias. In Entry 2, a primary phenylthiocar-bonate ester is used as the radical source. In Entry 3, the allyl group is introduced at a rather congested carbon. The reaction is completely stereoselective, presumably because of steric features of the tricyclic system. In Entry 4, a primary selenide serves as the radical source. Entry 5 involves a tandem alkylation-allylation with triethylboron generating the ethyl radical that initiates the reaction. This reaction was done in the presence of a Lewis acid, but lanthanide salts also give good results. 

The success of such reactions depends on the intramolecular hydrogen transfer being faster than hydrogen atom abstraction from the stannane reagent. In the example shown, hydrogen transfer is favored by the thermodynamic driving force of radical stabilization, by the intramolecular nature of the hydrogen transfer, and by the steric effects of the central quaternary carbon. This substitution pattern often favors intramolecular reactions as a result of conformational effects. 

In the first systematic study on nucleophilic substitutions of chiral halides by Group IV metal anions, Jensen and Davis showed that (S )-2-bromobutane is converted to the (R)-2-triphenylmetal product with predominant inversion at the carbon center (Table 5)37. Replacement of the phenyl substituents by alkyl groups was possible through sequential brominolysis and reaction of the derived stannyl bromides with a Grignard reagent (equation 16). Subsequently, Pereyre and coworkers employed the foregoing Grignard sequence to prepare several trialkyl(s-butyl)stannanes (equation 17)38. They also developed an alternative synthesis of more hindered trialkyl derivatives (equation 18). 

Stannanes bearing aliphatic groups with unsaturation in the carbon chain are grouped in Table 3, including both open-chain and cyclic vinyl-, allyl- and alkynylstannanes. 

In the second class of reactions, stannanes are added to carbon-carbon it bonds. This enables either (i) the direct addition of a labelled tin atom to an organic substrate when the tin atom is isotopically labelled, or (ii) the introduction of an unlabelled tin group that is subsequently replaced by another isotopically labelled atom such as 36C1, to give a labelled compound. These two types of reactions are discussed separately in the following paragraphs. 

The trialkylstannyl intermediates required in this synthetic sceme to prepare labelled compounds can be obtained in several ways. One method is the addition of the organotin hydride to the carbon-carbon triple bond of an alkyne (equation 93). These reactions have already been discussed in detail above. A second approach is to add a trialkylstan-nylvinyllithium to a ketone (equation 95), and a third method involves adding trialkylstan-nyllithium to a /J-halo, a, /J-unsaturated ester (equation 96). Although this last reaction gives a suitable trialkylstannane, these stannanes have proven to be inert in the destanny-lation reaction and, therefore, have not been used extensively to prepare radiolabelled compounds. 

Like most aryl halides, furyl halides and furyl triflates have been coupled with a variety of organostannanes including alkenyl, aryl, and heteroaryl stannanes in the presence of catalytic palladium. Carbamoylstannane 66 was prepared by treating lithiated piperidine with carbon monoxide and tributyltin chloride sequentially. The Stille reaction of 66 and 3-bromofuran then gave rise to amide 67 [61]. In another example, lithiation of 4,4-dimethyl-2-oxazoline followed by quenching with MesSnCl resulted in 2-(tributylstannyl)-4,4-dimethyl-2-oxazoline (68) in 70-80% yield [62], Subsequent Stille reaction of 68 with 3-bromofuran afforded 2-(3 -furyl)-4,4-dimethyl-2-oxazoline (69). 

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