Sodium borohydride, with cerium chlorid

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

Recent methods for the cleavage of allyl ethers that have that have yet to be tested on the anvil of complex target synthesis include (a) diborane generated in situ by reaction of sodium borohydride with iodine in THF at 0 °C (cyanoT ester, nitro, acetonide and tetrahydropyranyl groups survive) 434 (b) cerium(Ill) chloride and sodium iodide in refluxing acetonitrile (benzyl. THP and Boc groups survive) 435 (c) iodotrimethylsilane in acetonitrile at room temperature 436 and (d) DDO in wet dichloromethane (secondary allyl ethers, benzyl, acetate and TBS groups survive).437... 

Sodium borohydride and potassium borohydride react regioselectively with the formyl group of alkyl 2-formylcyclopropanecarboxylates lithium aluminum hydride is unseleetive. Stereospecific reduction of the formyl group was observed when formyl-cyclo-propanes were subjected to yeast alcohol dehydrogenase. ei Furthermore, regiospecific reduction of the aldehyde function in a 2-cyclopropylprop-2-enal derivative was performed using a mixture of sodium borohydride and cerium(III) chloride. 

Alternatively, the hydroxy group can be converted to the tosyl ester168 or replaced by chlorine108,169 followed by a base-catalyzed elimination. 1-Benzoxepin-5-(4//)-one is reduced with cerium(III) chloride/sodium borohydride to the hydroxy derivative. After conversion to the p-toluenesulfonate, the double bond is formed in 2 upon treatment with potassium tert-pen-toxide.168... 

In the special case of a-alkyl-a -nitro-substituted imines, reduction with sodium borohydride/ cerium(III) chloride and elimination of the chiral auxiliary generated the nitroalkene without racemization22. 

Oxo-4//-pyrido[l,2-a]pyrimidine-7-carboxylates 500 were obtained when 7-iodo-4T/-pyrido[ 1,2-a]pyrimidines 499 reacted with carbon monoxide in the presence of bis(triphenylphosphine)palladium(II) chloride catalyst and triethylamine (Scheme 29) (94MI2). From 7-iodo derivatives 499, 7-vinyl derivatives 501 and 7-(l-ethoxyvinyl) derivatives 502 were prepared with vinyltributyltin in the presence of Pd(PPh3)4 and with (1-ethoxy-vinyl)tributyltin in the presence of bis(triphenylphosphine)palladium(II) chloride catalyst, respectively, in toluene at 80°C. 7-(l-Ethoxy vinyl)pyr-ido[l, 2-a]pyrimidin-4-ones 502 were hydrolyzed to yield 7-acetyl derivatives 503. The acetyl group of compounds 503 was reduced with sodium borohydride in the presence of cerium(III) chloride in ethanol to give 7-(1 -hydroxyethyl)pyridopyrimidin-4-ones 504. 

Methadone hydrochloride (600.0 mg,1.74 mmol) was dissolved in ethanol (10 ml) and the solution was stirred whilst sodium borohydride (3.47 mmol) was added portion-wise over a period of 5 min. When the addition was complete a spatula end of cerium (III) chloride heptahydrate was added. The resultant solution was allowed to stir at room temperature for 30 min then the ethanol was removed under reduced pressure. The residue was portioned between diethyl ether (40 ml) and water (40 ml). The aqueous layer was extracted with more diethyl ether (2 times 20 ml) and then the combined organics were washed with brine (40 ml) and dried (MgS04). The ether was removed under reduced pressure to leave 435.0 mg, (80%) of 6-dimethylamino-4,4-diphenyl-3-heptanol. 

Reduction of the enone 147 with sodium borohydride-cerium(Ill) chloride in methanol gave a 2 1 mixture of the unsaturated alcohols. 

Warren has used a variation of his phosphine oxide-based olefination method to synthesise single isomers (E or Z) of unsaturated carboxylic acids.23 a-Diphenylphosphinoyl ketones (32) are reduced by sodium borohydride to give diastereomeric mixtures of the corresponding alcohols (33) and (34). These alcohols can be converted to the lactones (35) and (36) which can be separated and individually converted stereospecifically into (Z)-(37) and (E)-(38) alkenes by base treatment (Scheme 6). In many cases it is possible to reduce p-ketophosphine oxides (39) and enones (41) stereoselectively to the ery/Aro-alcohols (40) and (42), respectively, using sodium borohydride in the presence of cerium chloride (Scheme 7).24 An earlier report that reduction in the presence of cerium salts did not cause reversal of stereochemistry compared to reduction with borohydride alone appears to be true only of the compounds studied in that report. The carbanions of 3-hydroxypropylphosphine oxides (43) have been reported to undergo O- to C-acyl transfer to give the p-ketoalkylphosphine oxides... 

The Luche reduction involves a selective 1,2-reduction of a,p-unsaturated aldehydes and ketones using sodium borohydride in combination with cerium(III) chloride, resulting in the formation of allylic alcohols.1... 

Reduction of enones. Sodium borohydride in combination with catalytic amounts of cerium chloride reduces a,/8-unsaturated ketones selectively to allylic alcohols. Reactions proceed within 5 minutes even at 20°. ... 

To a solution of 100 mg (2R)-2-((lR)-hydroxy-l-hept-3-yn-2-one)-l-[((15, 2R)-2-(1-methyl- 1-phenylethyl) cyclohexyoxy) carbonyl]-5-(triisopropylsilyl)-2,3-ciihydro-4-pyridone (0.161 mmol) in 7 mL methanol was added 66 mg cerium(III) chloride heptahydrate (CeCl3 7H20, 0.177 mmol) in one portion. After being stirred for 10 min, the mixture was cooled to —50°C, and 9 mg sodium borohydride (0.241 mmol) was added. The reaction mixture was stirred for an additional 10 min, quenched with 10 mL water, and extracted with CH2CI2 (3 x 10 mL). The combined extracts were dried over MgS04 and concentrated under reduced pressure. The residue was purified by radial PLC (silica gel, 30% EtOAc/hexanes) to give 96 mg (2R)-2-((lR,25)-dihydroxy-hept-3-yne)- -[((15,2R)-2-( 1-methyl- 1-phenylethyl)-cyclohexyloxy)carbonyl]-5-(triisopropylsilyl)-2,3-dihydro-4-pyridone as a colorless oil, in a yield of 96%. 

The chiral allene 1, after treatment with MCPBA, DBU (to effect a C- 0 migration of the silyl group) then sodium borohydride-cerium(III) chloride gives 2 as a precursor to branched alditol and aldose derivatives."... 

This method was also applied to the reduction of natural products, using cerium(lll) chloride with sodium borohydride to minimize the formation of saturated alcohols and give good yields of allylic alcohols with good stereoselectivity (Luche et al., 1978). 

The selective reduction of the carbonyl function of a [4.4.4.]-propellatrienone to an allylic alcohol has been carried out with cerium(III) chloride-doped sodium borohydride (Paquette et al., 1984) en route to a unique tetraene derivative. 

Nicolaou and coworkers have reported an expeditious IBX (2-iodo3gr-benzoic acid, l-hydro q -l, 2-benziodoxol-3(l//)-one 1-oxide) mediated synthesis of Z-vancosamine " starting from vinyl iodide and protected aldehyde via an intramolecular Kishi-Nozaki coupling reaction. The coupling product, as a mixture of alcohols, was immediately oxidized with DMP (Dess-Martin periodinane). The oxidation was followed by a sodium borohydride/cerium chloride reduction to produce a protected alcohol intermediate. In the next step, the required alcohol was reacted... 

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