Transmetalation allylic stannanes

Certain S- and e-oxygenated allylic stannanes have been found to transmetallate with SnCU to give chiral pentacoordinated chloro stannane intermediates which add stereos-electively to aldehydes (Scheme 31)74. These reactions proceed with net 1,5-and 1,6-asymmetric induction. 

As well as alkenylstannanes [106-108], other classes such as a-heteroatom-substituted alkyltributylstannanes [109] and, more importantly, allylic stannanes [110, 111] also undergo these Sn-Cu transmetalations. Otherwise difficult to prepare, allylic copper reagents may, however, be obtained by treatment of allylic stannanes (produced in turn from organolithium, magnesium, or zinc organometallics) with Me2CuLi LiCN. They enter into cross-coupling reactions with alkyl bromides [110] or vinyl triflates (Scheme 2.52) [111]. 

The transmetallation process was extended to the preparation of vinylboranes709,710, and the superior reactivity of organotins over organosilicons was elegantly demonstrated by Williams and coworkers for the preparation of the optically active allylborane 24 from the corresponding allylic stannane in the total synthesis of (—)-Hennoxazole A711 (equation 54). 

Indium trichloride-mediated addition of (i )-a-(methoxymethoxy)allylic stannane (>95% ee) to cyclohexanecarbox-aldehyde affords the anti-adduct predominantly (anti syn = 98 2) and stereoselectively (>95%ee) (Equation (12)). Production of a transient allylic indium reagent is postulated via a stereosepecific anti-Se2 transmetallation. This a-(methoxymethoxy)allylic stannane reacts without allylic inversion, whereas the reaction of crotylstannane in Equation (5) (Section 9.14.3.3.1) proceeds with net allylic inversion. <5-Oxygenated allylic stannane also undergoes transmetallation with InCl3, and in situ addition to a-ODPS acetaldehyde leads mainly to the //-adduct, which is a potential precursor to D-(+)-altrose (Scheme 31).149,150... 

Transmetalations of Chiral Oxygenated Allylic Stannanes 10.12.1 SnCU... 

Figure 13. Reaction pathway for transmetalation of d-oxygenated allylic stannanes and their ensuing addition to aldehydes.

Table 42. Transmetalation-addition of e-oxygenated allylic stannanes.

Attempts to access enantioenriched /3 ,y-dioxygenated allylic stannanes through Lewis acid-catalyzed 1,3-isomerization of the a,d-dioxygenated isomers were unsuccessful owing to the facile elimination of BusSnOR from these intermediates (Eq. 60) [76]. Transmetalation with InCls in the presence of an aldehyde proceeds without elimination, however, to afford the anti adduct as the major diastereomer (Table 44). In additions to unbranched aldehydes, higher yields were obtained with... 

The generation of allylic indium reagents by transmetallation of allylic stannanes with InCl3 and subsequent reaction of these with aldehydes represents an important advance for diastereoselective synthesis of homoallylic alcohols [203]. In these reactions, the stannane is added to a premixed solution of the aldehyde and InCl3 in acetone. In this way, the reaetion of cyclohexanecarboxaldehyde with the 2-butenylindium reagent affords a 98/2 antilsyn mixture of homoallylic alcohols (Scheme 10-104). 

Benzaldimines have been reported to give high yields of condensation products with allylic stannanes, in the presence of palladium catalysts, under neutral conditions. Studies support transmetalation of the stannane to yield a bis-7r-allylpalladium complex, which binds imine 190 for allyl transfer. In the case of the catalyst 191, the chiral allyl ligand is not transferable, but determines facial selectivity in the optically emiched amine 192 (80% ee) (Scheme 5.2.42). 

Recent reports of the rapid transmetalation of the highly functionalized allylic stannane 216 (Scheme 5.2.49) leads to the trichloro species 217, which provides for greater Lewis acidity and increased reactivity compared to the parent trialkyl reagent. Although transmetalation assumes a dynamic equilibrium of 217 and 218, optimized allylation conditions using SnCU (1.0 equivalent) give the syn,anti-product 219 in 96% yield. 

The efficient transmetalation of allylic stannanes to allylboron reagents has generated an attractive methodology for asymmetric allylation. Corey and coworkers first described the use of enantiomers of bromoborane 228 (Scheme 5.2.51) for mild and quantitative transmetalation of allylstannane to yield the allylboron reagent 229. i The asymmetry in the bis-toluenesulfonamide of 228 is derived from l,2-diamino-l,2-diphenylethane, and both antipodes are readily available in high optical purity, by resolution of the starting diamines producing (R,R)- and (5, 5 )- Stein chiral auxiliaries in transmetalation product 229. 

Scheme 5.2.51 Use of the Stein chiral auxiliary in transmetalations of allylic stannanes...

Williams and coworkers have expanded the utility of this methodology via the application to highly functionalized substrates. transmetalation with R.R)-ot (S,S)-228 is quantitative and dependable, with a variety of allylic stannanes with C-2 substitution. Carbon chains at C-2 of the allyl component may contain additional functionality, including benzyl and allyl ethers, silyl ethers, esters, alkenes, halogens, or thioacetals, as well as stereogeificity. Asymmetric induction in the condensation with aldehydes is dominated by the chiral auxiliary. In this fashion, the allylation reaction may be designed as a convergent... 

In addition, the asymmetric allylation was utilized to address the issues of stereocontrol at C37 and C38 in the construction of the acyclic carbon chain of 234 (Scheme 5.2.53). Reactions of the sensitive /3,y-unsaturated aldehyde 241 were effected upon transmetalation of stannane 240 using (R,R)-22S,... 

The use of InCls for Lewis acid activation of aldehyde substrates leads to rapid transmetalation of the allylic stannane, followed by carbonyl addition reactions of an allyl indium reagent. Premixing of InCb and the allylic stannane in the absence of aldehyde often produces precipitation and poor results. On the other hand, allyl indium reagents have been independently prepared by several procedures, including reductive metalations. Several important reviews describe the methods of preparation and the reactivity of allyl indium compounds. This discussion will be limited to key factors regarding the transmetalation of allylic stannanes in the presence of aldehydes. Stereochemical events leading to the production of anti adducts as major products are illustrated in Scheme 5.2.55. 

Scheme 5.2.56 Examples of reactions involving transmetalations with InCIs 5.2.12 Reactions of Chiral Allylic Stannanes...

The allylation of aldehydes with allyhc bromide in water, in the presence of stoichiometric amounts of InClj and Sn, proceeds cleanly to give the corresponding anti y-adducts predominantly (Scheme 8.16) [7b[. It has been postulated that transmetalation from allylic stannane to allyllic indium via an S, 2 process occurs during this reaction the high anti selectivity can be explained in terms of a sixmembered ring transition state. 

Most of the catalytic methods reported so far are the chiral metal compound-catalyzed allylation reactions using allylic silanes or allylic stannanes. Two types of catalytic mechanism, Lewis acid mechanism and transmetallation mechanism, can be considered for these reactions as illustrated in Scheme 2. If the chiral metal catalyst acts as a Lewis acid in the asymmetric allylation, an al-... 

This allylation protocol was used in the total synthesis of amphidinolide to give homoallylic alcohol 12 in 72% yield and 17 1 dr (eq 5). Initial transmetallation of stannane 10 with (R,R)-1 via allylic transposition yielded an intermediate borane. Introduction of aldehyde 11 at -78 °C provided for a facile condensation reaction leading to 12. Stereocontrol was induced from the 1,2-diphenylethane sulfonamide auxiliary and could be predicted from a Zimmerman-Traxler model with minimized steric repulsions. The high level of selectivity obtained in this case was a result of a matched diastereomeric transition state featuring the inherent Felkin-Ahn selectivity for nucleophilic attack in aldehyde 11, with the (5)-configuration of the benzoate of 10, as well as the (7 ,7 -antipode of auxiliary 1, resulting in threefold stereodifferentiation. 

Instead of using allyl stannanes in the reaction, Loh et al. used a Sn/InCls system to achieve the allylation reactions between allylic bromides and aldehydes in water with moderate to excellent yields and good diastereoselectivities [31]. The in situ generation of the allyl stannane followed by the previously discussed transmetallation with InCls through a Se2 mechanism was surmised. Thus, the... 

Transmetalation of the appropriate allyl(tributyl)- or allyl(triphenyl)stannanes with butyllithi-um or phenyllithium offers a convenient and clean access to 2-propenyllithium 25,26,27. 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

Lewis acids, particularly the boron trifluroride diethyl ether complex, are used to promote the reaction between allyl(trialkyl)- and allyl(triaryl)stannanes and aldehydes and ketones52-54. The mechanism of these Lewis acid promoted reactions may involve coordination of the Lewis acid to the carbonyl compound so increasing its reactivity towards nucleophilic attack, or in situ transmetalation of the allyl(trialkyl)stannane by the Lewis acid to generate a more reactive allylmetal reagent. Which pathway operates in any particular case depends on the order of mixing of the reagents, the Lewis acid, temperature, solvent etc.55- 58. 

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