Chiral tin hydride

Scheme 14 Hydrogen atom transfer through a chiral tin hydride...

There can be two kinds of chiral tin reagents tin chiral and C-chiral. Early reports of chiral tin hydride involved transfer of chirality via a chiral tin center [45-47]. These tin hydrides were prone to racemization. Thus, chiral carbon-based ligands attached to the tin center were synthesized to minimize racemization. The first chiral tin hydride containing a C2-symmetric binaphthyl substituent was reported by Nanni and Curran (Scheme 16) [48]. a-Bromoketone 58 was reduced by chiral tin hydride 59 (R3 = Me), where the reactivity and selectivity was dependent on the reaction conditions (entry 4). 

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. 

Metzger and co-workers have also described a reduction of a-bromoesters by chiral tin hydrides containing a diastereomeric mixture of 2-[(l-dimethyl-aminoalkyl)phenyl] (DAAP) ligands [51]. The observed enantioselectivities were dependent on the tin hydride used and on the substituents attached to the radical center. 

Chiral solvation, in polysilane PSS induction, 3, 622 Chiral tin hydrides, applications, 9, 346 Chloranilato anionic rhodium complexes, synthesis, 7, 210 Chloride ligands... 

Both enantiomers of 4-A7/-butyM,5-dihydro-3//-dinaphtho[2,l -r 1, 2 - ]stanncpin 52 were synthesized and used for the enantioselective reduction of a-bromo esters 315. By using the achiral hydride sodium cyanoborohydride (NaBH3CN), the radical reductions proceeded enantioselectively with only catalylic amount of chiral tin hydride (Equation 56) <2003TA3069>. 

PM3, ab initio HF-default options available within the MOPAC 93 Structure optimization of the chiral tin hydride 1997AGE235 2003TA3069... 

Another approach to enantioselective reductions involves reactions with chiral tin hydrides. The helical chirality of the binaphthyl group has been taken advantage of in the design of chiral tin reagents. An example of an enantioselective reduction using chiral tin hydride 88 is shown in Eq. (13.26) [38]. The reduced products are formed in low enantiomeric excesses (41 % ee) and low chemical yields (often under 50%). These factors and the difficulty in synthesizing the chiral tin hydride reagents serve to diminish the utility of these types of enantioselective reductions thus far. 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

Deuterated and tritiated tin hydrides have been used to prepare deuterated saccharides93 and tritiated steroids46 from alkyl bromides, (equations 68 and 69). It is important to note that isomerization has occurred at the chiral reaction centre in the saccharide reaction (equation 68). For the steroid, the tin hydride reaction is regiospecific, i.e. it only reacts at the more reactive bromide rather than the less reactive chloride site and does not react with the keto group, the hydroxyl group or the acetal group. 

Recently, Kang and Kim developed new chiral ferrocenyl tin hydride derivatives 72 and 73 (Scheme 19) [60]. The authors screened the new chiral reagent in the reduction of a-bromoesters. Using one equivalent of 73 good ee s were obtained for ester 71. One drawback for this reagent, however, is the lengthy synthetic route for its preparation. 

Our approach was to use the unsaturated bromodeoxylactones in an intramolecular radical reaction, since these compounds possess both the radical precursor and the radical trap within the same molecule. Thus, reacting the unsaturated bromodeoxyheptonolactone 20 (Scheme 14) with tributyltin hydride and a radical initiator, the bicyclic lactone 65 a was obtained in a quantitative yield within 1 h. The stereocontrol in the reaction was determined by the structure of the product, since the compound obtained has two fused cyclopentane rings which can only be cis anellated. The radical A, which is the intermediate, was trapped by the tin hydride. The stereochemistry of the newly formed chiral center is determined by the configuration at C-4 in the educt 20 [45]. 

An enantioselective reduction of an a-iodolactone under radical conditions has been reported [95CC481]. Treatment of 207 with tin hydride, magnesium(II) iodide and in the presence of a chiral amine gave the 8-lactone 208 in good yield and moderate enantioselectivity. This is one of the first examples of chiral Lewis acid mediated enantioselective radical reactions. 

TABLE 44. Diastereomeric ratios of the chelate tin halides and hydrides with a stereogenic tin atom containing a chiral tin atom and N-donor substituent... 

The first test of the chiral /V-acylhydrazones was in tin-mediated radical addition [47,48]. Addition of isopropyl iodide to propionaldehyde hydrazone 3a was chosen for initial screening (Scheme 2). Using the tin hydride method with triethylborane initiation [51, 52] (Bu3SnH, Et3B/02), with InCl3 and ZnCU as Lewis acid additives, desired adduct 13a was obtained with high diastereoselectivity. In contrast, 13a was produced with poor selectivity (diastereomer ratio, dr 2 1) in the absence of Lewis acid. 

Addition of 1 equiv. of Lewis acid to free-radical reduction by the tin hydride bearing chiral menthyl groups leads to a remarkable increase of the enantioselectivity (Equation (18)).63 64... 

Data related to the enantioselectivity of organotin hydrides containing chiral PhN ligand in free radical reductions have been published . Reaction of the tin hydrides 233a and 233c with methanol was also reported to proceed with abstraction of H2 and formation of the methoxy derivatives Me2PhNSnOMe and MePhPhNSnOMe, respectively . 

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