Aldehydes, reduction with tributyltin hydride

The products here are acyl selenides, which can be reduced to the corresponding aldehydes in high yields by a Pd-catalyzed reduction with tributyltin hydride... 

Hydrostannation of carbonyl compounds with tributyltin hydride is promoted by radical initiation and Lewis or protic acid catalysis.The activation of the carbonyl group by the acidic species allows the weakly nucleophilic tin hydride to react via a polar mechanism. Silica gel was a suitable catalyst allowing chemoselective reduction of carbonyl groups under conditions that left many functional groups unchanged. Tributyltin triflate generated in situ from the tin hydride and triflic acid was a particularly efficient catalyst for the reduction of aldehydes and ketones with tributyltin hydride in benzene or 1,2-di-chloromethane at room temperature. Esters and ketals were not affected under these conditions and certain aldehydes were reduced selectively in preference to ketones. 

Reductive removal of the halogen was achieved with tributyltin hydride and subsequent ozonolysis gave aldehyde 221. An aldol condensation of 221 with the trimethylsilyl enol ether of methyl propionate, followed by Jones oxidation... 

Further details of phase-transfer addition of dibromocarbene to a,(3-unsaturated esters and ketones [e.g. (18)] and subsequent reductive monode-bromination with tributyltin hydride (Vol. 7, p. 34) have been publishedJulia reports the use of solid NaOH-Et3NCH2Ph CP for the solid-liquid phase-transfer catalytic generation of dichlorocarbene (addition to a-pinene and limonene). Dichlorocarbene also provides a mild and efficient method for the Beckmann fragmentation of anh-a-hydroxy-ketoximes into aldehydes (or ketones) and nitriles [e.g. 2-exo-hydroxy-3-hydroxyiminobornane into (24 X = CHO, Y = CN)]. Trimethylsilylcyclopropanes are synthesized by adding the... 

Tin metal is used sparingly as a reducing metal in modem organic synthesis, which contrasts with tin derivatives such as tributytin hydride, which are common. Aldehydes, for example, are readily reduced with tributyltin hydride (Bu3SnH) in aqueous media. An example is the reduction of 2-naphthaldehyde to the alcohol (396) in 93% yield in refluxing methanol.5l5 when this reaction was done in water, and 85% yield of 396 was obtained. 

Selective reduction of aldehydes. In the absence of radical initiators, tributyltin hydride does not ordinarily reduce carbonyl groups. However, when slurried in cyclohexane with dried silica gel (activated by heating at 220° under reduced pressure), this hydride reduces aldehydes and ketones to alcohols in high yield. The rate of reduction is aldehydes > dialkyl ketones > aryl alkyl ketones > diaryl ketones. Thus it is possible to reduce aldehydes selectively. The function of Si02 apparently is that of a mild acid catalyst. 

Under radical conditions tributyltin hydride reduced a-chlorocarbonyl compounds to the corresponding saturated carbonyl derivatives but in the presence of phosphine oxides (HMPA or BU3PO) chemose-lective reduction of the carbonyl group was observed. a-Chloro ketones and aldehydes were reduced with this reagent combination to give good yields of the chlorohydrins. The choice of ligand was important as neither phosphines nor amines were effective substitutes for the phosphine oxides. 

Tin Hydrides. Tributyltin hydride reduces aldehydes to primary alcohols by simply heating in methanol. °° A mixture of BusSnH and phenylboronic acid (p. 815) reduces aldehydes in dichloromethane. °° Reduction of ketones was achieved with Bu2SnH2 and a palladium catalyst. ° Using triaryltin hydrides with Bp3 OEt2, where aryl is 2,6-diphenylbenzyl, selective reduction of aliphatic aldehydes in the presence of a conjugated aldehyde was achieved. 

The magnesium-mediated reductive trifluoromethylation also works for other structurally diverse chlorosilanes. Chlorotriethyl-silane, f-hutyldimethylsilyl chloride, and tris(trimethylsilyl)silyl chloride have been applied to prepare corresponding trifluoro-methyl-containing silanes. However, the reductive trifluoromethylation did not take place with other electrophiles such as aldehydes, ketones, allyl bromide, benzyl chloride, or tributyltin chloride. Even tributyltin hydride and allyltrimethylsilane showed no reactivity The reason for such behavior is not clear. Probably, chlorosilanes play an important role during the reductive trifluoromethylation both as a silylating agent and a single-electron transfer promoter. 

Tributyltin hydride was subsequently tested in the conversion of acid chlorides to the aldehydes (Scheme 15).D6],[47] jjjg homogeneous catalyst Pd(Ph3P)4 as well as Pd(ll) complexes, such as PdCl2, can be used instead of a supported catalyst. The reaction proceeds under very mild conditions, especially compared to the Rosemnund reduction, and affords the aldehydes in very good yield. The reaction tolerates a variety of functional groups and can even convert a,/3-unsaturated acid chlorides to the a,/S-unsatu-rated aldehydes. Without the Pd the tin hydrides will reduce the acid chloride by a radical mechanism to a mixture of aldehydes and esters. With the Pd the reaction is much more rapid and selective for the aldehyde. The reaction has been applied to the synthesis of a-amino aldehydes (Scheme and a nicotinaldehyde derivatives ... 

Along the same means, the tributyltin hydride reduction of thioesters and sele-noesters to aldehydes with palladium catalysis was reported (Scheme 27). A detailed discussion of the mechanism was presented. 

In our earlier publication (15) the synthesis of the southern part was described. This is shown in Scheme 2, including some improvements. The diene ester prepared from methacrolein and trimethyl-phosphonoacetate >3 underwent a Diels Alder cyclization with methyl vinyl ketone to give only one regio isomer, which after equilibration with base gave the all trans keto ester 9, in an overall yield of 75%. Linder Wadsworth Emmons conditions, 9 reacted smoothly with the t-butyl dimethylphosphonoacetate 10 to give the a, p unsaturated ester 11. Hydrolysis, followed by acid chloride formation and reduction with n-tributyltin hydride gave the aldehyde 12 the yield over 4 steps was 70%. 

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