Sodium cyanoborohydride reductive methylation using

A practicable strategy to provide access to chiral pyrazolidine-3-carboxylic acid (16) makes use of asymmetric dipolar cycloaddition of diazoalkanes to u,p-unsaturated carboxylic acid derivatives. For this purpose a chiral auxiliary of the alkene component is used, e.g. Op-polzer s1166 1671 (lf )-2,10-camphorsultam.t164l As shown in Scheme 7, by reaction of (tri-methylsilyl)diazomethane (41) with /V-( aery I oy I )cam p h ors u 11 am (42), the AL(4,5-dihy-dropyrazoline-5-carbonyl)camphorsultam (43) is obtained. Reduction of 44 with sodium cyanoborohydride leads to A-(pyrazolidine-3-carbonyl)camphorsultam (45) as the 35-dia-stereoisomer (ee 9 1) in 65 to 80% yields.[164] The camphorsultam 45 is then converted into the methyl ester 46 by reaction with magnesium methylate without racemizationj1641... 

Methyl acetals and ketals are rapidly reduced to methyl ethers by sodium cyanoborohydride in methanol with dry HCI at ice temperatures. A dioxolane is completely cleaved to a methyl ether, showing intervention by the solvent at some stage (equation 14), but when an inert solvent such as THF is used only single cleavage occurs this reagent shows interesting selectivity in the reduction of benzylidene acetals in the carbohydrate series (see Section 1.9.3.4). 

Reductive cyclization has been used in a novel, recent synthesis of the alkaloids ( )-isoretronecanol (22) and ( )-trachelanthamidine (23) by Borch and Ho. Condensation of the dianion derived from methyl acetoacetate with Z-l,4-dichlorobut-2-ene, followed by cyclization with sodium meth-oxide yielded the cycloheptenone ester intermediate (32) (Scheme 2). Reductive amination of this ketoester with sodium cyanoborohydride and ammonium nitrate gave a mixture of the diastereoisomeric aminoesters 33 and 34. Oxidation with osmium tetroxide and periodate, followed by reductive cyclization, again using sodium cyanoborohydride, gave the two pyrrolizidine esters 35 and 36 in a ratio of 1 2 [gas-liquid chromatography (GLC) analysis]. The esters were separated by preparative layer chromatography, and lithium aluminum hydride reduction of the individual esters gave the two pyrrolizidine alkaloids 22 and 23. 

Synthesis from aldonolactones The synthesis of p-homonojirimycin (2) from tetra-(9-benzyl-D-glucono-1,5-lactone (56) (Scheme 8) was achieved by treatment of the latter with (methoxymethoxy)methyl lithium to give the a-D-gluco-heptulose derivative 57, which underwent reduction with LiAlITj to produce a mixture of heptitols 58 (1 1 ratio). Oxidation of 58 using Swern oxidation (DMSO-TFAA) gave the heptodiulose 59. Compound 59 was immediately submitted to reductive amination using ammonium formate in the presence of sodium cyanoborohydride to produce 60 in 50% yield from 58. Removal... 

Reductive amination with formaldehyde and sodium cyanoborohydride provides a convenient method for methylation of a secondary amine (or dimethylation of a primary amine). An alternative procedure uses formaldehyde together with formic acid (HCOOH) as the source of hydride in what is termed the Eschweiler-Clark reaction. Deprotonation of formic acid provides the formate anion, which delivers hydride to the iminium ion with concomitant formation of carbon dioxide. 

The thought was, maybe N-methylate this compound, then put on an isopropyl group with reductive alkylation, using acetone as the carbon source and sodium cyanoborohydride. Towards this end, the free base of 2C-T-7 (from one gram of the hydrochloride) was refluxed for 2 h in 1.3 g butyl formate, and on removing the solvent/reactant the residue spontaneously crystallized. This formamide (0.7 g) was reduced with... 

Attaching of fluorescent probes to PLP has also been used to determine PLP. Chauhan and Dakshinamurti employed reductive amination of PLP with methyl anthranilate and sodium cyanoborohydride to form a highly fluorescent amine (83). Durko et al. (54) prepared diphenyl-isobenzofurane derivatives of Be vitamers to enable fluorometric measurement of vitamin Be. However, the use of fluorescent probes are generally not suitable for routine analytical work, mainly because the unreacted fluorescent probe may interfere in Be vitamer quantification (83). 

The selective reduction of an cu-iodo-group without affecting an azido-group can be achieved using sodium cyanoborohydride in HMPT oj-toluene-p-sul-phonates can also be reduced using a mixture of sodium iodide and sodium cyanoborohydride in the same solvent. For example, reduction of methyl 2-azido-3,4-di-0-benzyl-2,6-dideoxy-6-iodo-a-D-altropyranoside by this procedure gave methyl 2-azido-3,4-di-0-benzyl-2,6-dideoxy-a-D-altropyranoside. 

The cyclopalladation of allylic or homoallylic amines and sulfides proceeds due to the chelating effect of N and S atoms, and has been used for functionalization of alkenes. For example, i-propyl 3-butenyl sulfide is carbopalladated with methyl cy-clopentanecarboxylate and Li2PdCl4. Reduction of the chelated complex with sodium cyanoborohydride affords the alkylated keto ester in 96% yield (eq 24). Functionalization of 3-N,N-dimethylaminocyclopentene for the synthesis of a prostaglandin skeleton has been carried out via a IV-chelated palladium complex as an intermediate. In the first step, malonate was introduced regio- and stereoselectively by carbopalladation (eq 25). Elimination of a /3-hydrogen generated a new cyclopentene, and its oxypalladation with 2-chloroethanol, followed by insertion of 1-octen-3-one and /3-elimination, afforded the final product. 

An efficient new route for the reductive cleavage of acetals to methyl ethers involves sodium cyanoborohydride in acid [equation (12 a)]. ° The same type of process can also be performed on the acetals of aliphatic aldehydes and ketones using what is believed to be a Ti° species [equation (12 )]. ° ... 

---