Reduction With Silanes Hydrosilylation

Silane hydrides can be used for the reduction of carbonyls and alkenes. Reaction of methylcyclohexene with a mixture of triethylsilane (EtsSiH) and trifluoroacetic acid (CF3CO2H) reduced the alkene moiety to give methylcyclohexane in 72% yield. 2 Under the same conditions, however, 1-pentene was not reduced. More commonly, this reagent is used for reduction of conjugated carbonyls, probably via formation of a silyl enolate (secs. 9.2, 9.3.B) as in the reduction of cyclohexenone to cyclohexanone in 85% yield with Ph2SiH2. Addition of transition metals such as ZnCl2, or copper salts to the silane facilitates the reduc-tion,594 as in the conversion of 576 to 577 in 96% yield.  

Ketones and aldehydes are reduced by silanes in acid media, as in the reaction of cyclohexanone with Et3SiH and trifluoroacetic acid to give cyclohexanol in 74% yield. The reaction is selective for 1,2-reduction of aldehyde moieties, as in the reduction of 3-phenyl-prop-(2 )-enal to 3-phenylprop-(2 )-en-l-ol in 

95% yield).596 Another example of such selectivity is the reduction of the ketone unit in 2-bromo-l-phenylpropanone to give 2-bromo-l-phenyl-1-propanol in 70% yield.543 Ketones are usually reduced faster 

Asymmetric reduction involving silanes is possible when a chiral additive is used. An example is reduction of acetophenone to f) )-phenethyl alcohol (578) in 99% yield and 84.2% ee in the presence of 579.599 

The functional group transforms observed in this section are 

---

Part two (section 3) deals with the hydrosilylation of unsaturated carbon-heteroatom bond, mostly 0=0 and 0=N (but also C N, and C=S), as a catalytic method for the reduction of C=0 and C=N bonds—one of the most fundamental transformations in organic chemistry. Catalytic hydrosilylation of prochiral ketones and imines with substituted silanes and siloxanes that can provide (if followed by hydrolysis) convenient access to chiral alcohols and amines, respectively, discussed from the catalytic and synthetic point of view completes this part. 

Catalytic Hydrosilylation of Unsaturated Carbon-Heteroatom Bonds. Hydrosilylation of ketone produces silyl ether, which can be easily converted to alcohol via an additional hydrolysis (deprotection) step (Scheme 28). Analogously, hydrosilylation of imine leads to the formation of silylamine, which can be conveniently transformed to amine. Hydrosilylation of carbonyl (imine) group with subsequent hydrolysis is often referred to as the reduction by silanes. 

Buchwald reported an important advance in enantioselective C=N reductions with the chiral titanocene catalyst 186 (X,X = l,l -binaphth-2,2 -diolate) [137]. The reduction of cyclic imines with 186 and silanes afforded products with high selectivity however, reductions of acyclic imines were considerably less selective. It was suggested that this arose from the fact that, unlike cyclic imines, acyclic imines are found as mixtures of equilibrating cis and trans isomers. An important breakthrough was achieved with the observation that in situ activation of the difluoride catalyst 187 (X = F) gave a catalytically active titanium hydride species that promotes the hydrosilylation of both cyclic and acyclic amines with excellent enantiomeric excess [138]. Subsequent investigations revealed that the addition of a primary amine had a beneficial effect on the scope of the reaction [138, 139]. A demonstration of the utility of this method was reported by Buchwald in the enantioselective synthesis of the alkaloid frans-solenopsin A (190), a constituent of fire-ant venom (Scheme 11.29) [140]. 

Bis(allyl)homoallyloxysilanes 56a and 56b are designed for a tandem intramolecular silylformylation-allylsUylation reaction, which has turned out to be an efficient approach to construct polyol and polyketide frameworks [21], For example, heating a solution of 56 in benzene at 60 °C in the presence of Rh(acac)(CO)2 under CO atmosphere followed by the Tamao oxidation gives syn,syn-triols 59 stereoselectively via oxasilacyclopentanes 57 and 58 (Scheme 5.14). Bis(ds-cro-tyl)silane 56b is readily prepared by double Pd-catalyzed 1,4-hydrosilylation of 1,3-butadiene with dichlorosilane followed by reduction with UAIH4 and alcoholysis with the corresponding homoallylic alcohol. 

With alkyl- and arylsilanes, concurrent isomerization and hydrosilylation occur, but the rates of both processes fall away rapidly due to some reduction to the metal such deactivation is temperature-dependent, and high yields of adduct are obtained with these silanes when additions are carried out slowly at ambient temperature. 

C-C bond formation mediated by silane.6,6a 6f With respect to the development of intramolecular variants, these seminal studies lay fallow until 1990, at which point the palladium- and nickel-catalyzed reductive cyclization of tethered 1,3-dienes mediated by silane was disclosed. As demonstrated by the hydrosilylation-cyclization of 1,3,8,10-tetraene 21a, the /rarcr-divinylcyclopentanes 21b and 21c are produced in excellent yield, but with modest stereoselectivity.46 Bu3SnH was shown to participate in an analogous cyclization.46 Isotopic labeling and crossover experiments provide evidence against a mechanism involving initial diene hydrosilylation. Rather, the collective data corroborate a mechanism involving oxidative coupling of the diene followed by silane activation (Scheme 15). 

The reaction of thiyl radicals with silicon hydrides (Reaction 3.18) is the key step of the so called polarity-reversal catalysis in the radical-chain reduction of alkyl halides as well as in the hydrosilylation of olefins using silane-thiol couple (see Sections 4.5 and 5.1) [33]. The reaction is strongly endothermic and reversible (Reaction —3.18). 

Diyne cyclization/hydrosilylation catalyzed by 4 was proposed to occur via a mechanism analogous to that proposed for nickel-catalyzed diyne cyclization/hydrosilylation (Scheme 4). It was worth noting that experimental evidence pointed to a silane-promoted reductive elimination pathway. In particular, reaction of dimethyl dipropargylmalonate with HSiMc2Et (3 equiv.) catalyzed by 4 led to predominant formation of the disilylated uncyclized compound 5 in 51% yield, whereas slow addition of HSiMe2Et to a mixture of the diyne and 4 led to predominant formation of silylated 1,2-dialkylidene cyclopentane 6 (Scheme 5). This and related observations were consistent with a mechanism involving silane-promoted G-H reductive elimination from alkenylrhodium hydride species Id to form silylated uncyclized products in competition with intramolecular carbometallation of Id to form cyclization/hydrosilylation products (Scheme 4). Silane-promoted reductive elimination could occur either via an oxidative addition/reductive elimination sequence involving an Rh(v) intermediate, or via a cr-bond metathesis pathway. 

Titanium-catalyzed cyclization/hydrosilylation of 6-hepten-2-one was proposed to occur via / -migratory insertion of the G=G bond into the titanium-carbon bond of the 77 -ketone olefin complex c/iatr-lj to form titanacycle cis-ll] (Scheme 16). cr-Bond metathesis of the Ti-O bond of cis- iij with the Si-H bond of the silane followed by G-H reductive elimination would release the silylated cyclopentanol and regenerate the Ti(0) catalyst. Under stoichiometric conditions, each of the steps that converts the enone to the titanacycle is reversible, leading to selective formation of the more stable m-fused metallacycle." For this reason, the diastereoselective cyclization of 6-hepten-2-one under catalytic conditions was proposed to occur via non-selective, reversible formation of 77 -ketotitanium olefin complexes chair-1) and boat-1), followed by preferential cyclization of chair-1) to form cis-11) (Scheme 16). 

Ojima has proposed a mechanism for the rhodium-catalyzed cyclization/silylformylation of enynes that invokes several of the same intermediates proposed for the rhodium-catalyzed cyclization/hydrosilylation of enynes (Scheme 7). Silylmetallation of the G=G bond of the enyne followed by / -migratory insertion of the pendant G=G bond into the resulting Rh-G bond could form rhodium cyclopentyl complex Illf. a-Migratory insertion of GO into the Rh-G bond of Illf followed by silane-promoted reductive elimination from the resulting rhodium formyl complex rVf could release the silylated cyclopentane carboxaldehyde with regeneration of silylrhodium hydride complex If (Scheme 7). 

The hydrosilylation of carbonyl compounds with polymethylhydrosiloxane (PMHS) or other alkoxysilanes can be catalyzed by TBAF, at high efficiency [9]. The asymmetric version of this process has been developed by Lawrence and coworkers using chiral ammonium fluoride 7c prepared via the method of Shioiri [10]. The reduction of acetophenone was performed with trimethoxysilane (1.5 equiv.) and 7c (10 mol%) in THF at room temperature, yielding phenethyl alcohol quantitatively with 51% ee (R) (Scheme 4.6). A slightly higher enantioselectivity was observed in the reduction of propiophenone. When tris(trimethylsiloxy)silane was used as a hydride source, the enantioselectivity was increased, though a pro-... 

Not surprisingly, chiral formamides emerged as prime candidates for the development of an asymmetric variant of this reaction. A selection of the most efficient amide catalysts based on amino acids is shown in Figure 7.4 representative examples of enantioselective hydrosilylation are collected in Tables 7.7 and 7.8. Proline-derived anilide 82a and its naphthyl analogue 82b, introduced by Matsu-mura [3c], produced moderate enantioselectivity in the reduction of aromatic ketimines with trichlorosilane at 10 mol% catalyst loading (Table 7.7, entries 1 and 2). Formamide functionality proved to be crucial for the activation of the silane, as the corresponding acetamides failed to initiate the reaction. 

Reductive TVansformations. The utility of 1 was first demonstrated in the enantioselective hydrosilylation of ketones. Uniformly high enantioselectivity, yield, and turnover were observed for aromatic (and some aliphatic) ketones when using the complex derived from RhCls (eq 1). Lower enantioselection is observed with t-Bu-pybox or i-Pr-pybox cobalt(I). The derived l Sn(OTf)2 complex gives alcohol products with up to 58% ee using methano-lic polymethylhydrosiloxane. A cationic ruthenium(III) catalyst diverts the usual reduction pathway to enolsilane formation, particularly when the nature of the silane is modified (eq 2). ... 

Conjugated dienes like 1,3-dienes give 1 1 adducts of various types usually 1,2- and 1,4-addition products, and the regio- and stereo-isomers of each type, but also 1 2 adducts, and dimerization and reduction products. The product distribution depends on the kinds of dienes, silanes and particularly on the kind of catalyst. Of these, chromium hexacarbonyl is specific for the formation of (Z)-crotylsilanes from butadienes. Similar (Z)-selective hydrosilylation is observed with HSiCb and [Pd(PPh3)4] catalyst. The reaction pattern of 1,3-butadiene is summarized in Scheme 8. 

Bromine and chlorine react with vinylsilanes to afford vinyl bromide and chloride with net inversion of configuration. Addition of these halogens proceeds with anti stereochemistry. Elimination of halo-silane in the presence of a nucleophile like F or RO also is assumed to take place in an anti manner (Scheme 16). The same transformation using iodine is applicable only to 1,2-dialkylvinylsilanes. The process is a reliable method for the preparation of vinyl halides of defined configuration. The reactions are not, overall, reductions, and they are included here only to emphasize the usefulness of the products of hydrosilylation. 

SCHEME 18.10 Formation of polycarbosilanes by Pt-catalyzed hydrosilylation of vinyl-silanes. The catalyticaUy active species is [PtCb] which is in situ generated by reduction of HjPtClj with PrOH. Characteristic reaction steps are A Ugand substitution, B oxidative addition of Si-H, C H-migration, and D reductive eUmination of the carbosilane. ... 

---