Clean reduction

With this encouraging result from the model system, a gram quantity of the racemic sulfoxide 40 was prepared by oxidation of benzoxathiin 16 with mCPBA and a small amount of chiral sulfoxide (A)-40 with 94% ee was isolated by subsequent chiral HPLC separation (Scheme 5.12). When chiral sulfoxide (S)-40 was treated with borane-dimethylsulfide, a clean reduction of the olefin and the sulfoxide was observed. More surprisingly, only the desired cis-diaryl dihydrobenzoxathiin 12 was observed in high yield and unchanged 94% ee. No trans-isomer or 16 was observed. With this proof of concept in hand, an efficient... 

Nickel boride, formed in situ from sodium borohydride and nickel chloride, has been used to prepare dihydro derivatives from thiothymine 385 <2001JME1853> and thiobarbituric acid derivatives 388 <2002J(P1)2520>. With 4-thiothymine derivatives, an isomeric mixture of 3,4- and 3,6-dihydro derivatives 386 and 387 was obtained <2001JME1853>, but with 2-thiobarbiturates, clean reduction at the 2-position was able to be achieved <2002J(P1)2520>. 

After the solvent is added, the septum is replaced with a reflux condenser, topped with an N2-CO gas outlet, which is connected to a mineral oil bubbler. The reaction mixture is stirred at reflux for 12 h, and a slow N2 purge is maintained throughout this period. After cooling to room temperature, the gray-green powder is isolated by filtration, washed with 2 x 50 mL of fresh chlorobenzene, followed by 4 x 50 mL of hexane, and dried in vacuo (10 storr, 25 °C, 8h). It is important to free the product of all traces of chlorobenzene in order to obtain clean reductions in the following syntheses. Yield 47 g (or 96% based on WC16). 

Likewise die carbon radical abstracts the hydrogen from tin much more readily than other C-H hydrogens. Thus the process is clean from a mechanistic point of view and consequently leads to clean reduction products. 

Reduction of CoNiFg was not accomplished with CjFg, nor with H2 at room temperature, but in a pressure vessel at 350 °C, clean reduction to CoNip4 was achieved ... 

Action of alkyl Grignard reagents with a variety of alkyl halides (except Mel, which undergoes methylation [377]) in the presence of a palladium catalyst usually resulted in clean reduction of the halides, rather than alkylation or elimination [Eq. (159) 378,379]. 

A recent article by Swenton et al.I04 reported deuterium incorporation via the reduction of halides with a zinc-copper couple. They found that freshly prepared zinc-copper couple in dry ether solvents with heavy water as the deuterium source effects clean reduction of dibromocyclopropanes to their monobromo derivatives. In a second system, they104 found that dichloroketene adducts underwent clean reduction to the corresponding cyclobutanones... 

The fj-nitrobenzyl and p-nitrobenzyl ethers can be prepared and cleaved by many of the methods described for benzyl ethers. In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate 280 nm, 95% yield of nucleotide ). This is one of the most important methods for cleavage of this ether. These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative." Clean reduction to the aniline is accomplished with Zn(Cu) (acetylacetone, rt, >93% yield).Hydrogenolysis is also an effective means for cleavage. A polymeric version of the o-nitrobenzyl ether has been prepared for oligosaccharide synthesis that is also conveniently cleaved by photolysis. An unusual selective deprotection of a bis-o-nitrobenzyl ether has been observed. The photochemical reaction of o-nitrobenzyl derivatives has been reviewed. ... 

SmL, DMPU, 50-97% yield. The reaction works well for alkyl-substituted aziridines benzenesulfonamides react faster than tosyl amides. Primary toluenesulfonamides do not give clean reductive cleavage, but benzenesulfonamides do. 

Reduction of 11 to polyphosphine 12 was attempted using a HSlCl3/Et3N reagenf ut resulted in the formation of a small amount of an unidentified unit ( ISZ) in addition to the desired phosphine units 12. A novel clean reduction method, therefore, has been developed (14). The method is an one-pot reaction. In which Is first treated with (COCI2) and then with I-BU2AIH, giving rise to the polyphosphine... 

Electrochemical methods provide another way of removing the alkanethiolate mono-layer from the gold and silver surfaces291,292. Thiolates are cleanly reductively desorbed at potentials of ca > —1.5 V in a process which is a reverse reaction of monolayer formation. This makes it possible to use electrochemical desorption for determination of surface coverage of alkanethiol monolayers (equation 3)291. 

The ff-t5Tpe ethoxycarbonyl radical is on the contrary less nucleophilic than the acetyl radical (Table 29) in this Ccise the unpaired electron occupies a hybrid orbital and the incipient positive charge in the transition state cannot be stabilized by the lone-pair electron of the alkoxy group, as with the alkoxyalkyl radical, so that only the inductive effect is working and a clean reduction of nucleophilicity is observed. The remarkable fact is therefore that the same substituent, an a-alkoxy group, produces opposite polar effects depending on the electronic configuration of the carbon-centered radical. 

The reductive ring opening of 330a with sodium cyanoborohydride/titanium tetrachloride in acetonitrile occurs with no ester reduction whatsoever to provide 421 in 83% yield. Subsequent conversion to the tosylate followed by reduction with lithium borohydride/lithium triethylborohydride affords in 61% yield the crystalline diol 422. Lithium aluminum hydride or sodium borohydride reduction of the tosylate of 421 fails to produce clean reductions to 422. Epoxide ring closure of 422 is achieved with two equivalents of sodium hydroxide in methanol to fiimish in 93% yield (2 S, 3i )-2-benzyloxy-3,4-epoxybutan-l-ol (423) [140] (Scheme 94). 

We have developed a clean reduction protocol for aldehydes and ketones that uses alumina supported NaBH4 under microwaves (46). No side product formation is observed in any of the reactions investigated and the reaction does not occur in the absence of alumina. The process in its entirety involves a simple mixing of carbonyl compound with (10%) NaBH4-alumina under MW irradiation for O.S-2 min (Scheme 17). The useful chemoselective feature of the reaction is a]q>arent fimn the reduction of rranr-cinnamaldehyde (cinnamaldehyde/NaBH4-alumina, 1 1 mol equivalent) wherein the olefinic moiety remains intact and only the aldehyde functionality is reduced rapidly at room t nperature. 

Other possible relays are mostly alkynes, which, after carbopalladation, undergo a surprisingly clean reductive demetallation with formic acid salts (Scheme 2). At this point it is crucial that the catalyst cocktail has the appropriate composition, as yields under different conditions can vary substantially. The high degree of regioselectivity starting from propynoic acid amides has been attributed to coordination with the amide functionality. 

The clean reduction, however, is achieved [4c] using 15 mmol of neat solution of (i )-Alpine-Borane and acylcyanide (10 mmol). The progress of the reaction is monitored by ff NMR (appearance of a-pinene signal at 5.2 ppm). The reaction mixture is then treated with methanol containing cobaltous chloride [21], followed by the addition of sodium borohydride (Eq. 26.12) [4c]. 

It has been shown earlier that the presence of electron-withdrawing ligands favors the reductive elimination in palladium 77 -allyl complexes. Benzoquinone has been used to perform the clean reductive elimination in -allyl aryl palladium complexes, that otherwise decompose by other competing routes such as /3-H elimination. The intermediate complex with a coordinated benzoquinone molecule has been characterized in solution (Scheme 72). Benzoquinones have also been used to promote the reductive elimination of chloro and an -allyl Cl as a nucleophile toward Pd 77 -allyls usually attacks in a trans- (or exo-) fashion. A different stereochemistry (cis- or /rrfo-attack) has been achieved in this work. It was found that the more electron withdrawing the quinone the more favored the m-attack, as supported by theoretical calculations. Allyltin trichloride can be obtained by a reductive elimination reaction from Pd(SnCl3)(77 -allyl)L. The reaction is accelerated by addition of an electron-withdrawing olefin such as allyl chloride. Tin dichloride also increases the reaction rate. ... 

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