Tributyltin hydride reduction with

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

Tributyltin hydride reduction of carbonyl compounds. The reduction of carbonyl compounds with metal hydrides can also proceed via an electron-transfer activation in analogy to the metal hydride insertion into TCNE.188 Such a notion is further supported by the following observations (a) the reaction rates are enhanced by light as well as heat 189 (b) the rate of the reduction depends strongly on the reduction potentials of ketones. For example, trifluoroacetophenone ( re<1 = —1.38 V versus SCE) is quantitatively reduced by Bu3SnH in propionitrile within 5 min, whereas the reduction of cyclohexanone (Erea — 2.4 V versus SCE) to cyclohexanol (under identical... 

The reaction of alkyl dihalogenoacetate magnesium enolates with 2,3-isopropylidene-D-glyceraldehyde affords the expected /3-hydroxy-a-dihalogenoesters . The erythro isomer is obtained with isopropyl dichloroacetate magnesium enolate. This result is in agreement with theoretical models. 2-Deoxy-pentono-1,4-lactones are obtained after removal of the halogen atom by either Raney nickel or tributyltin hydride reduction (equation 89). 

The tributyltin hydride reduction of dihaloaziridines, e.g. (266), represents another example where the ring system has been maintained (79CJC1958). Especially noteworthy is the retained configuration associated with the reaction. This behavior differs from the cyclopropyl analog and was explained on the basis of increased s-character in the exocyclic bond caused by the nitrogen atom. 

The iodocyclization of 4-methyl-5-hexenoic acid performed under conditions of thermodynamic control (iodine in acetonitrile in the absence of a base) leads to the preferential formation of the /raw.v-diequatorial 5-lactones (94 6) in 77% yield1. Similar results were observed starting from (S)-4-methyl-5-hexenoic acid (1), obtained from citronellol, with iodine in acetonitrile, followed by tributyltin hydride reduction. The 5,6-dimethylvalerolactone 2 was obtained in 40%) yield and 93.5 6.5 (irans/cis) diastereoselcctivity 2. 

Organotin hydride reductions of a variety of polycyclic halides containing three-membered rings have been studied, including the stereoselectivity in the triphenyltin hydride reduction of 6jS-chloro-3,5-cyclocholestanes, Tributyltin hydride reduction of both syn- and anti-1-chloro-2-methylnortricyclene (35) afforded cn fo-5-methylnorbornene (36) as the major product, with very little of the e.w-isomer. ... 

Ring cleavage was extremely rapid in the tributyltin hydride reduction of 9-bromotricyclo-[3.3.1.0 ]nona-3,6-diene (9-bromobarbaralane, 43) excellent yields of bicyclo[3.2.2]nona-2,6,8-triene (44) were isolated, mixed with only a trace of the unrearranged barbaralane. ... 

A variation of the tributyltin hydride reduction is available that can be applied to alcohols. The alcohol is converted to a thionocarbonate and then reduced with BusSnH and AIBN, which circumvents the need for... 

Completion of the formal synthesis of ( + ) carpetimycin A 48 was effected by tributyltin hydride reduction of the bromohydrin 43, to give predominantly the required cis a-hydroxyalkyl P-lactam 46 in 63% yield, together with the... 

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. 

Another type of reactivity was disclosed for difluorochloro group in pyrimidine series. Recently Iaroshenko, Langer and co-workers shown that difluorochloro substituted pyrimidines 1227 can be converted into corresponding difluoromethyl pyrimidines 1228 by radical reduction with tributyltin hydride in the presence of AIBN in moderate yields. In addition, CFaCl-substituted pyrimidines 1227 were transformed to the corresponding l,l-difluorobut-3-enyl pyrimidines 1129 by reaction with aUyltributyltin and AIBN. In this case the yields of transformation are lower in comparison with tributyltin hydride reduction (Schane 269) [412]. 

Most functional group conversions abxmdantly used on carbohydrate derivatives are also compatible with thioglycosides, e.g. SN2-displacements of sulfonates [37], azo transfer [38], and deoxygenation by tributyltin hydride reduction of o-carbonyl carbamates [39]. During oxidations care has to be taken so not to obtain the sulfoxide derivative (if that is not desired). DMSO and also PDC-mediated oxidations can usually be performed without problems [40]. 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Methylation of avermectins B and B2 leads to the corresponding derivatives of the A series (49). A procedure involving the oxidation of the 5-methoxy group with mercuric acetate and NaBH reduction of the 5-keto-intermediate allows the conversion of the A to the B components (50). The 23-hydroxy group of the "2" components, after selective protection of the other secondary hydroxy groups, is converted to a thionocarbonate, which can be elirninated to give the 22,23-double bond of the "1" components alternatively it can be reduced with tributyltin hydride to the 22,23-dihydro derivatives (= ivermectins) (51). 

Cyclopropenone was flrst synthesized " by the hydrolysis of an equilibrating mixture of 3,3-dichlorocyclopropene and 1,3-dichloro-cyclopropene (prepared by reduction of tetrachlorocyclopropene with tributyltin hydride). This procedure has been adapted - to prepare... 

The triply benzo-fused pyrrolonaphthyridine 222 results by reduction of either 220 or 221 with tributyltin hydride and AIBN. This compound shows biological activity similar to 215 above, although interestingly 222 is more active in the protonated form (Equation 57) <2001J(P1)3180>. 

A method for tributyltin in sediments consists of extraction with anhydrous acetic acid, hydride generation, cold trapping and end analysis by GC-AAS using a quartz furnace75. Reduction with NaBFLi followed by solvent extraction, concentration and GC-FPD was proposed for simulaneous determination of di- and tributyltin residues in sea water LOD 10 ng/L for 1 L sample, with 87.1-98.4% of Sn recovery76. 

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. 

Another complication that can arise in these reactions is that a cycloaddition reaction of the radical intermediate formed in the tin hydride reduction, to an adjacent carbon-carbon double bond, can compete with the simple reduction reaction. This occurs when a five- or six-membered ring can be formed in an intramolecular cycloaddition reaction. For example, Beckwith and Lawrence96 found both five- and six-membered rings in the product when l-bromo-2,2,5-trimethylhex-l-ene was treated with tributyltin hydride (Scheme 15). 

John and coworkers78 also observed cyclization to a five-membered ring heterocycle in their hydride reduction of methyl 6/i-isothiocyanatopenicillanate with both tributyltin hydride and triphenyltin hydride (Scheme 16). John and coworkers also found this type of ring closure when an isocyanide was reduced with tributyltin deuteride. The mechanism of this arrangement (Scheme 17) has been confirmed by deuterium labelling. 

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