Hydride sources

Aldehydes can also be prepared by the carbonylation of aryl and alkenyl halides and triflate, and benzyl and allyl chlorides using tin hydride as a hydride source and Pd(PhjP)4 as a catalyst[377]. Hydrosilancs arc used as another hydride source[378]. The arenediazonium tetralluoroborate 515 is converted into a benzaldehyde derivative rapidly in a good yield by using Et ,SiH or PH MS as the hydride source[379]. 

Hydrogenolysis of aryl and alkenyl halides and triflates proceeds by the treatment with various hydride sources. The reaction can be explained by the transmetallation with hydride to form palladium hydride, which undergoes reductive elimination. Several boro hydrides are used for this purpose[680], Deuteration of aromatic rings is possible by the reaction of aryl chlorides with NaBD4681]. 

Formate is an excellent hydride source for the hydrogenolysis of aryl halides[682]. Ammonium or triethylammonium formate[683] and sodium formate are mostly used[684,685]. Dechlorination of the chloroarene 806 is carried out with ammonium formate using Pd charcoal as a catalyst[686]. By the treatment of 2,4,6-trichloroamline with formate, the chlorine atom at the /iiara-position is preferentially removed[687]. The dehalogenation of 2,4-diha-loestrogene is achieved with formic acid, KI, and ascorbic acid[688]. 

The /3,7-unsaturated aldehyde 407 is prepared in good yields by the carbo-nylation of an allylic chloride under mild conditions using tributyltin hydride as a hydride source[261]. Aldehydes are obtained in moderate yields by the reaction of CO and H2[262],... 

The Pd-catalyzed hydrogenolysis of allylic compounds by various hydrides gives alkenes. From terminal allylic compounds, either 1-alkenes or 2-alkenes are formed depending on the hydride sources [360a]. 

Formic acid behaves differently. The expected octadienyl formate is not formed. The reaction of butadiene carried out in formic acid and triethylamine affords 1,7-octadiene (41) as the major product and 1,6-octadiene as a minor product[41-43], Formic acid is a hydride source. It is known that the Pd hydride formed from palladium formate attacks the substituted side of tt-allylpalladium to form the terminal alkene[44] (see Section 2.8). The reductive dimerization of isoprene in formic acid in the presence of Et3N using tri(i)-tolyl)phosphine at room temperature afforded a mixture of dimers in 87% yield, which contained 71% of the head-to-tail dimers 42a and 42b. The mixture was treated with concentrated HCl to give an easily separable chloro derivative 43. By this means, a- and d-citronellol (44 and 45) were pre-pared[45]. 

Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

For the use of dimethylamine-borane as an alternative hydride source, see David, H., Dupuis, L., Guillerez, M.-G., Guibe,... 

Iron hydride complexes can be synthesized by many routes. Some typical methods are listed in Scheme 2. Protonation of an anionic iron complex or substitution of hydride for one electron donor ligands, such as halides, affords hydride complexes. NaBH4 and L1A1H4 are generally used as the hydride source for the latter transformation. Oxidative addition of H2 and E-H to a low valent and unsaturated iron complex gives a hydride complex. Furthermore, p-hydride abstraction from an alkyl iron complex affords a hydride complex with olefin coordination. The last two reactions are frequently involved in catalytic cycles. 

Hydroalumination of terminal alkenes using EtjAl as the hydride source must be carried out with titanium catalysts [24], since zirconium compounds lead to the formation of alumacyclopentanes [60, 61] (Scheme 2-11) and carbometallated products [62]. Suitable substrates for hydroalumination include styrene, allylnaphthalene and vinylsilanes. Only one of the ethyl groups in EtjAl takes part in these reactions, allowing the synthesis of diethylalkylalanes, which are difficult to obtain by other methods. 

Nickel catalysts promote the hydroalumination of alkenes using trialkylalanes R3AI and dialkylalanes such as BU2AIH as the aluminum hydride sources [9, 29, 30, 33]. However, exhaustive studies of the range of substrates capable of hydroalumination with these reagents has not been carried out. Linear terminal alkenes like 1-octene react quantitatively with BU3AI at 0°C within 1-2 h in the presence of catalytic amounts of Ni(COD)2 [30]. Internal double bonds are inert under these conditions, whereas with 1,5-hexadiene cycHzation occurs. 

In 2000, Woodward et al. reported that LiGaH4, in combination with the S/ 0-chelate, 2-hydroxy-2 -mercapto-1,1 -binaphthyl (MTBH2), formed an active catalyst for the asymmetric reduction of prochiral ketones with catecholborane as the hydride source (Scheme 10.65). The enantioface differentiation was on the basis of the steric requirements of the ketone substituents. Aryl w-alkyl ketones were reduced in enantioselectivities of 90-93% ee, whereas alkyl methyl ketones e.g. i-Pr, Cy, t-Bu) gave lower enantioselectivities of 60-72% ee. 

Et2Zn also participates in the reductive coupling as a formal hydride source. Results for the Ni-catalyzed, Et2Zn-promoted homoallylation of carbonyl compounds with isoprene are summarized in Table 7 [30]. Et2Zn is so reactive that for the reaction with reactive aromatic aldehydes it causes direct ethylation of aldehydes, and the yields of homoallylation are diminished (runs 1 and 2). Unsaturated aldehydes seem to be subject to the Michael addition of Et2Zn. Accordingly, for the reaction with cinnamaldehyde, none of the expected homoallylation product is produced instead, the 1,4-addition product of Et2Zn, 3-phenylpentanal is produced exclusively (run 3). 

TiCl4 promotes reduction of carbonyl groups or acetals with R3SiH or R3SnH (Scheme 24) Other hydride sources are also effective.91 ... 

Another route to the formation of piperidine heterocycles is cyclization via reductive animation utilizing various hydride sources. The scheme below depicts a bis reductive animation, using sodium triacetoxyborohydride as the hydride source, to generate exo-178 and endo-179 azabicyclo[3.2.1]octane amino acids in moderate yields <06JOC8467>. 

Gheorghe et al. make use of sodium cyanoborohydride as a hydride source in the synthesis of 5-arylpiperidines <06OL1653>. Kellehar and Kelly report the formation of a spiro -lactam using sodium borohydride in the key reductive animation step <06TL3005>. 

Limited studies of the germanium and tin hydride analogs of the silicon hydrides show that they share this ability to function as hydride sources in ionic hydrogenations however, their relatively greater reactivity toward acids appears to restrict their practical applications in organic synthesis.24,25... 

A synthesis of (-)-4a,5-dihydrostreptazolin was accomplished in a similar manner only a reductive palladium-catalyzed cyclization was utilized.104 The hydride source was polymethylhydroxysilane (PMHS), and the unprotected hydroxyl group of 174 (Equation (89)) had an accelerating effect, since the reaction was completed in minutes instead of hours, as in the example above. 

The vinylsilane C-Si bond can also be formed from a silane by reductive cyclization/hydrosilylation of a 1,6- or 1,7-diyne. Reductive cyclization of diynes is an important ring-forming method catalyzed by transition metals, and silanes are common reductants in this process. However, in many cases the silane serves only as a hydride source, and the silyl group is not retained in the isolated product.95 Here, the focus is on the more rare methods which allow simultaneous C-C bond formation and vinylsilane installation. 

Grigg discovered that a 5-exo-dig Pd-catalyzed cyclization of IV-acetylenic-o-haloanilines 291 to give 3-exo-alkylidene indolines 292 occurs in the presence of a hydride source, such as formic acid [346]. The reaction is stereoselective and regiospecific. 

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