Oxygenated Allylic Stannanes

10 Enantioenriched Oxygenated Allylic Stannanes 10.10.1 a-Oxygenated Allylic Stannanes 

Initial efforts in this area involved the addition of BuaSnLi to fratw-crotonaldehyde and conversion of the racemic hydroxy stannane adduct to diastereomeric (-)-menthyloxy-methyl ethers by reaction with (-)-menthyloxymethyl chloride (Eq. 32) [52]. These dia-stereomers could be separated by careful chromatography. They formed diastereomeric anti, (Z) adducts with aldehydes upon heating to 130 °C. The results parallel those seen for the racemic OMOM allylic stannanes (Table 25). Formation of the (Z) double bond in these adducts is attributed to steric interactions between the allylic OR substituent and the adjacent stannane butyl groups in a chair-like transition state as pictured in Eq. (9). The excellent stereoselectivity of these additions is suggestive of a highly ordered transition state. 

A sequence was later developed for the synthesis of enantioenriched a-oxygenated allylic stannanes that did not require resolution (Eq. 33) [53]. This sequence, like the former, starts with the addition of BusSnLi to an enal. The resulting lithio alkoxide is oxidized in situ to the corresponding acylstannane. Reduction of the acylstannane with (M)-BINAL-H affords the (5)-a-hydroxy allylic stannane in 95% ee. The use of (F)-BINAL-H leads to the (R) enantiomer with comparable ee. These hydroxy 

Significantly higher diastereoselectivity was observed in reactions with a-branched aldehydes as illustrated in Eq. (34) [54]. Here the (5)-a-methyl-/3-OMOM aldehyde substrate is matched with the (f )-a-OMOM stannane in a Felkin-Ahn acyclic transition state to afford the syn, syn adduct almost exclusively. 

An even more impressive example is illustrated in Eq. (35). In this example the enantioenriched aldehyde substrate is treated with excess stannane reagent consisting of a 1 1 mixture of diastereomers at the a-position. A kinetic resolution ensues with the (5)-stannane reacting preferentially to afford the syn, syn adduct exclusively. The recovered stannane is enriehed in the a- R) isomer. 

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A. y-Oxygen-Substituleel Stannanes. Oxygenated allylic stannanes have been synthesized and used advantageously in several types of syntheses. Both a- and y-alkoxy and silyloxy stannane can be prepared by several complementary methods.177 C-y-Alkoxy and silyloxy allylic stannanes react with aldehydes to give primarily syn... 

A second route to nonracemic /-oxygenated allylic stannanes utilizes an enantioselective deprotonation of allylic carbamates by BuLi in the presence of (—)-sparteine. The configurationally stable a-lithio carbamate intermediate undergoes enantioselective S/,-2 reaction with Bu3SnCl and Mc SnCI (Scheme 28)65. Once formed, the /-carbamoyloxy stannanes can be inverted by successive lithiation with. s-BuLi and stannation with R3SnCl (Scheme 29)65. The former reaction proceeds with S/.-2 retention and the latter by Sf2 inversion. Nonracemic allylic carbamates can also be used to prepare chiral stannanes. Deprotonation with. s-BuLi TMEDA proceeds stereospecifically with retention (Scheme 29)65. 

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. 

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... 

Additions of Achiral and Racemic Oxygenated Allylic Stannanes to Aldehydes... 

Both a- and y-oxygenated allylic stannanes add to aldehydes under thermal or Lewis-acid-promoted conditions. These reagents are less reactive and more acid-labile than their non-oxygenated counterparts. Consequently, the best results are obtained with relatively reactive aldehydes. Strong Lewis acids cannot be used because they tend to cause decomposition of the stannanes. Initial studies employed thermal conditions to effect the additions. Thus, the frans-a-OMOM crotylstannane, prepared from crotonaldehyde by addition of BuaSnLi and etherification of the alcohol adduct, afforded the anti-(Z) adduct upon treatment with benzaldehyde under reflux in toluene (Eq. 28) [46]. 

Upon treatment with a variety of mild Lewis acids, a-oxygenated allylic stannanes rearrange to the y isomers (Eq. 36) [56]. The process is stereospecific and highly regioselective. Thus (S)-a afford (5)-y-allylic stannanes, and vice versa, with essentially no loss of ee. 

Table 39. Additions of a y-oxygenated allylic stannane bearing a chiral ether auxiliary to achiral aldehydes. OH OH...

The presence of an a-alkoxy substituent on the substrate aldehyde leads to the formation of a differentially protected 1,2,3-triol upon addition of a y-oxygenated allylic stannane (Eq. 43). Such additions are of potential use for the synthesis of carbohydrates and extended polyols. The resident double bond in the adduct can be further functionalized by dihydroxylation or epoxidation to extend the polyol chain. 

The MgBr2-promoted additions are strongly substrate-controlled. As a result it is possible to effect kinetic resolution of racemic y-oxygenated allylic stannanes thereby circumventing the need to employ enantioenriched stannane. The degree of enantio discrimination is somewhat dependent upon the y-oxygen substituent as illustrated by the additions to a threonine-derived aldehyde given in Eq. (46) [66]. 

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.

This behavior contrasts with that of TiCU with which premixing of the stannane is essential for optimum formation of the anti adduct. The reaction can also be conducted with a-oxygenated allylic stannanes which also afford anti adducts (Eq. 54). 

Lewis-acid promoted cyclizations of allylic stannanes have been successfully employed to prepare macrocyclic compounds. An enantioenriched a-oxygenated allylic stannane led to a 14-membered cembrane precursor in high yield with excellent diastereoselectivity (Eq. 64) [80]. 

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