Formates hydride donor

With less hindered hydride donors, particularly NaBH4 and LiAlH4, confor-mationally biased cyclohexanones give predominantly the equatorial alcohol, which is normally the more stable of the two isomers. However, hydride reductions are exothermic reactions with low activation energies. The TS should resemble starting ketone, so product stability should not control the stereoselectivity. A major factor in the preference for the equatorial isomer is the torsional strain that develops in the formation of the axial alcohol.117... 

Krische et al. demonstrated intramolecular reaction with Co(dpm)2 (5mol%) and PhSiH3 (120 mol %) as a hydride donor (Scheme 8) [14-16]. Addition of aldehyde-enone 17 to a solution of the Co catalyst and phenylsi-lane resulted in the formation of the corresponding aldol cyclization product... 

The chemistry here is similar to that for the basic alcoholic systems, but with formate (HC02 ) as the hydride-donor, and thus the reducing agent. In control runs with H20/K0H or C0/H20, little or no conversion was observed. 

Bimetallic activation of acetyl and alkoxyacetyl ligands — through formation of cationic P2 acyl complexes — to reaction with nucleophilic hydride donors was established. Cationic transition metal compounds possessing an accessible coordination site bind a neutral T -acyl ligand on another complex as a cationic P2 acyl system. These i2 3icyl systems activate the acyl ligand to reduction analogous to carbocation activation. Several examples of i2-acyl complexation have been reported previously. 

The reaction of [Ni(ethene)3] with a hydride donor such as trialkyl(hydrido)-aluminate results in the formation of the dinuclear anionic complex [ Ni(eth-ene)2[2l 11 [22]. The nickel(O) centers in this complex are in a trigonal planar environment of two ethene molecules and a bridging hydride ion, with the ethene carbons in the plane of coordination. The two planes of coordination within the dinuclear complex are almost perpendicular to each other, and the Ni-H-Ni unit is significantly bent, with an angle of 125° and a Ni-Ni distance of 2.6 A [22],... 

The most common catalysts for the Meerwein-Ponndorf-Verley reduction and Oppenauer oxidation are Alm and Lnm isopropoxides, often in combination with 2-propanol as hydride donor and solvent. These alkoxide ligands are readily exchanged under formation of 2-propanol and the metal complexes of the substrate (Scheme 20.5). Therefore, the catalytic species is in fact a mixture of metal alkoxides. 

Iodopyrroles 199 can be conveniently deiodinated with formate as the hydride donor in the presence of Pd(0) [145]. This transformation is particularly important in the synthesis of dipyrromethanes for porphyrins and for linear pyrroles. Interestingly, no reaction occurs in refluxing THF. 

Denitration of ally lie nitro groups " Allylic nitro compounds when com-plexed with Pd(0) are reductively removed by a variety of hydride donors. The regioselectivity of denitration to give 1- or 2-alkenes can be controlled by the choice of ligand and by the hydride donor. Thus reduction by formates gives 1-alkenes, and use of NaBH4 or NaBH,CN favors formation of 2-alkenes. 

Scheme 126 Electrocatalytic NAD(P)H regeneration with formate as a hydride donor.

Two current alternative views are available as to how remotely boimd NADPH may work. One sees its action as involving two successive one-electron oxidations (52, 53). The effectiveness of NADPH in preventing compound II formation is then due to the high reactivity of the NADP intermediate as reductant of the compound II generated in the first one-electron step. The other model (47) prefers to see NADPH as a hydride donor responsible for the almost simultaneous reduction of the ferryl iron and the protein radical species. 

Initial methane formation from methanol on the fresh catalyst is proposed to proceed on Bronsted acid sites as a reaction with a hydride donor - in... 

The results summarized in Scheme 5 indicate that in the presence of hydrogen, protic solvent, or hydride donors or acceptors, the formato ligand in (Ph3P)2Cu02CH is neither reduced nor transformed into organic formate (see below). 

Significantly better results in addition of non-stabilized nucleophiles have come from hydrogenolysis reactions using formate as a hydride donor as shown in Scheme 8E.46. The racemic cyclic acetate and prochiral linear carbonates were reduced in good enantioselectivities by monophosphine ligands (/ )-MOP (16) and (Zf)-MOP-phen (17), respectively [195]. The chirality of the allylsilane can be efficiently transferred to the carbinol center of the homoallylic alcohol by the subsequent Lewis acid catalyzed carbonyl addition reaction 1196], The analogous... 

This reaction allows the preparation of tertiary methylamines from secondary amines via treatment with formaldehyde in the presence of formic acid. The formate anion acts as hydride donor to reduce the imine or iminium salt, so that the overall process is a reductive amination. The formation of quaternary amines is not possible. 

Net hydride transfer may also occur in a stepwise fashion without radical intermediates. There may be a-bond formation between donor and acceptor, particularly when resonance stabilized cationic acceptors react with a donor containing nucleophilic lone pairs on heteroatoms (9). Plausible fragmentations then lead to the products of transfer to the cation of hydride 0- to the heteroatom. 

A requirement for an a/m-orientation of the hydridic p-C—H and C—metal bonds as in [10] is indicated by the reaction of threo-3-deuterio-2-(trimethylstannyl)butane with triphenylcarbenium tetrafluoroborate in methylene chloride at 24° which yields a mixture of 3-deuterio-l -butene, /ra v-2-deuterio-2-butene, and undeuteriated c/.v-2-butene as the major product (Hannon and Traylor, 1981). Comparison of the product distributions for the protio- and deuterio-stannanes yields primary and secondary isotope effects of 3.7 and 1.1 respectively. These reactions appear to avoid the complications of adduct formation between the triarylcarbenium salt and the hydride donor, but the preferential formation of the cw-2-butenes is not fully explained. The requirement for the anti-orientation is also shown by the relatively low hydride-donating properties of tris[(triphenylstannyl)methyl-methane (Ducharme et ai, 1984a) which adopts a C3-conformation with the P-C—H gauche to all three C—Sn bonds. In contrast, 1,3,5-triphenyl-2,4,6-trithia-1,3,5-tristannyladamantane, in which anti-orientations with respect to the bridgehead C—H bond are locked, shows high reactivity (Ducharme et al., 1984b). 

In the addition of hydride donors to aldehydes (other than formaldehyde) the tetrahedral intermediate is a primary alkoxide. In the addition to ketones it is a secondary alkoxide. When a primary alkoxide is formed, the steric hindrance is smaller. Also, when the C=0 double bond of an aldehyde is broken due to the formation of the CH(0 M ) group of an alkoxide, less stabilization of the C=0 double bond by the flanking alkyl group is lost than when the analogous transformation occurs in a ketone (cf. Table 9.1). For these two reasons aldehydes react faster with hydride donors than ketones. With a moderately reactive hydride donor such as NaBH4 at low temperature one can even chemoselectively reduce an aldehyde in the presence of a ketone (Figure 10.6, left). 

In additions of hydride donors to a-chiral carbonyl compounds, whether Cram or anti-Cram selectivity, or Felkin-Anh or Cram chelate selectivity occurs is the result of kinetic control. The rate-determining step in either of these additions is the formation of a tetrahedral intermediate. It takes place irreversibly. The tetrahedral intermediate that is accessible via the most stable transition state is produced most rapidly. However, in contrast to what is found in many other considerations in this book, this intermediate does not represent a good transition state model for its formation reaction. The reason for this deviation is that it is produced in an... 

Looking at all the reactions that took place for the formation of the complex C, the heterocycle A plays the role of a molecular glue, which is possible because it represents both a Lewis acid and a Lewis base. As a result of this dual role, A places the electrophile (the ketone) and the hydride donor (the BH3) in close proximity. In this way, the complex C makes possible a quasi-intramolecular reduction of the ketone. It takes place stereoselectively in such a way as the arrangement of the reaction partners in C suggests (Figure 10.26). As a bicyclic... 

M. M. Midland, L. A. Morell, K. Krohn, Formation of C-H Bonds by Reduction of Carbonyl Groups (C=0) - Reduction with Hydride Donors, in Methoden Org. Chem. (Houben-Weyl) 4th ed., 1952-, Stereoselective Synthesis (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), Vol. E21d, 4082, Georg Thieme Verlag, Stuttgart, 1995. 

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