Stannanes chiral—

Squaric acid 3-Cyclobutene-1,2-dione, 3,4-dihydroxy- (2892-51-5), 76, 190 Stannanes, chiral a-alkoxyallylic, 77, 103 Stereochemical purity, determination of, 76, 52... 

Cram erythro-products" (G.E. Keck, 1984 A, B, C). [3-(Silyloxy)allyl]stannanes and O-pro-tected a- or y -hydroxy aldehydes yield 1,2,3- or 1,2,4-triols with three chiral centres with high regio- and diastereoselectivity (G.E. Keck, 1987). 

A convenient route to highly enantiomerically enriched a-alkoxy tributylslannanes 17 involves the enanlioselective reduction of acyl stannanes 16 with chiral reducing agents10. Thus reaction of acyl stannanes with lithium aluminum hydride, chirally modified by (S)-l,l -bi-naphthalene-2,2 -diol, followed by protection of the hydroxy group, lead to the desired a-alkoxy stannanes 17 in optical purities as high as 98 % ee. 

Chiral organolead compounds 19 can be obtained, with retention of configuration, from the corresponding a-alkoxy stannanes via tin/lilhium exchange and transmetalation with bro-mo(tributyl)lcad12. 

Diallyldialkylstannanes with chiral alkyl substituents on the tin, show variable asymmetric induction in their Lewis acid catalyzed reactions with aldehydes. Using bis-(/f)-2-phenylbutyl-(di-2-propenyl)stannane, enantiomeric excesses of up to 54% were obtained via attack on the / e-face of the aldehyde96. 

The stannanes (-)-ent-12 and ( + )-ent- 3 (R = CH3) are obtained with >80% ee from the alkenyllithium (-)-sparteine complex105,107a (Section 1.3.3.3.1.1.). Hence, their titanium(IV) chloride mediated carbonyl additions are accompanied by chirality transfer and enantioface selection of opposite sense. This was demonstrated for the reaction with (5)-2-benzyloxy-propanal107b the d.r. (88 12) roughly reflects the enantiomeric composition of the stannanes. 

With chiral aldehydes, reagent approach is generally consistent with a Felkin model.163 This preference can be reinforced or opposed by the effect of other stereocenters. For example, the addition of allyl stannane to l,4-dimethyl-3-(4-methoxybenzyloxy)pentanal is strongly in accord with the Felkin model for the anti stereoisomer but is anti-Felkin for the syn isomer. 

Use of oxygenated stannanes with a-substituted aldehydes leads to matched and mismatched combinations.181 For example, with the y-MOM derivative and a-benzyloxypropanal, the matched pair gives a single stereoisomer of the major product, whereas the mismatched pair gives a 67 33 syntanti mixture. The configuration at the alkoxy-substituted center is completely controlled by the chirality of the stannane. 

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... 

The coupling of the achiral stannane 20 and aldehyde 21 was achieved with fair to good enantioselectivity and fair yield using chiral catalysts. Ti-BINOL gave 52% e.e. and 31% yield, whereas an acyloxyborane catalyst (see p. 127) gave 90% e.e. and 24% yield.189... 

The successful preparation of nonracemic tetraorganogermanes stimulated investigations on the synthesis of related stannanes. By the late 1960s, it was apparent from XH NMR studies that chiral stannanes should be capable of existence and that their stability... 

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). 

The first chiral a-oxygenated stannanes were prepared by Still59. Addition of Bu3SnLi to a-methy l-/J-phenylpropionaldehyde followed by MOMC1 led to a separable 1 1 mixture of syn and anti alkoxy stannanes (Scheme 26). Lithiation with n-BuLi and addition of acetone gave the respective adducts with overall retention of stereochemistry. Thus, it is implied that the intermediate a-alkoxy lithio derivatives retain their configuration. 

An alternative route to nonracemic a-alkoxy stannanes entails the reduction of acyl stannanes with chiral hydrides61 62. Accordingly, conjugated stannyl enones yield (S)-a-alkoxy allylic stannanes by reduction with (J )-(+)-BINAL-H. As expected, (S)-(—)-BINAL-H gives rise to the enantiomeric (7 )-a-alkoxy allylic stannanes (equation 29)61. Upon treatment with Lewis acids, these stannanes undergo a stereospecific anti 1,3-isomerization to the (Z)-y-alkoxy allylic stannanes61. 

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. 

A third route to nonracemic a-alkoxy and a-hydroxy stannaries employs the chiral acetal 73 prepared from (f ,f )-2,4-pentanediol (Scheme 30)66. Addition of various Grignard reagents to this acetal in the presence of TiCLt results in selective displacement yielding (S )-a-alkoxy stannanes. The corresponding a-hydroxy derivatives can be obtained after oxidation and mild base treatment. Organocuprates can also be employed to cleave this acetal but with somewhat lower selectivity67. 

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. 

An alternative synthesis of nonracemic a-amino stannanes is outlined in equation 3777. The diastereomeric stannanes, obtained by sequential lithiation and stannylation of the starting nonracemic piperidinooxazoline, can be separated by chromatography. Subsequent removal of the chiral auxiliary and N-methylation completes the synthesis. 

Dialkoxydialkyl stannanes cross-couple with derivatives of chiral tartaric acid, preserving the original chirality, as shown in reaction 32. The dialkylstannylene acetals produced in this reaction are useful reagents for synthesis of chiral compounds28611. 

Scheme 16 summarizes the results obtained by enantioselective radical reduction of a-bromoester by chiral binaphthyl-derived tin hydride. The reactions were generally performed at - 78 °C. An increase in the temperature resulted in the lowering of the selectivity. All reactions mediated by (S)-configured chiral tin hydride showed an (R)-selective preference in the product. The use of the opposite enantiomer of the chiral stannane resulted in a quantitative reversal of the selectivity (not shown). The selectivity remained modest on addition of magnesium Lewis acids. These reductions were also feasible when a catalytic amount of chiral tin hydride (1 mol %) was employed in combination with an excess of achiral hydride NaCNBH3, providing similar results. 

Thomas and co-workers have examined camphor-derived chiral stannanes recently [52], However, poor selectivity (< 5% ee) was obtained for the reduction of bromoketones in the absence of any Lewis acid. 

Although the Lewis acid greatly enhances the selectivity, the transfer of chirality is derived from the chiral ligand on the stannane. These deductions are supported by the fact that when stannane 67 is used, the ee of the product increases from 4% in the absence of a Lewis acid to 46% in the presence of achiral Lewis acid (Cp2ZrCl2) for substrate 63. When the enantiomer of 67 was used as the reductant, the product was obtained with the opposite configuration, which also supports the above-mentioned presumption. 

Scheme 18 Synthesis of a-amino acid derivatives use of chiral stannane...

The steric course of this two-step process was examined with several chiral secondary propargylic phosphates (Eq. 9.35) [40], The derived propargylic stannanes were found to be formed with net inversion of configuration. Based on previous evidence that the initial formation of the allenyltitanium intermediate occurs with inversion, it can be deduced that stannylation proceeds by a syn pathway. This surprising result was attributed to coordination between the chlorine substituent of the Bu3SnCl and the electropositive titanium center (Scheme 9.11). 

Reductive metallation of aldehydes (but not ketones) by tri-n-butyl-(trimethyisilyl)stannane to yield a-hydroxystannanes is catalysed by tetra-n-butylammonium cyanide [15]. Other phase-transfer catalysts are not as effective and solvents, other than tetrahydrofuran, generally give poorer conversions. Use of a chiral catalyst induced 24% ee with 3-phenylpropanal. 

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