Stoichiometric reducing agents

The catalytic cycle with Ni catalysts is generally similar. The essential difference is the deactivation process, which in this case occurs not via the formation of a precipitate of Ni°, but rather due to interception of the highly reactive Ni° species by any fortuitous oxidant, such as oxygen. As Ni11 is not so easily reduced to Ni° as Pdn is to Pd°, Ni-catalyzed systems often require the addition of a stoichiometric reducing agent (Zn, DIBAL-H, other hydride transfer agents, BuLi, etc.). 

Brook has effectively modified a procedure (introduced by Hosomi) which employs a trialkoxysilane as the stoichiometric reducing agent which, in the presence of amino acid anions reduces aryl alkyl ketones or diaryl ketones to the corresponding (A)-secondary alcohols, albeit in modest ee (generally 25 40%). ... 

The action of 7-rays on an aqueous solution of CO2 and ferrous ion gives fair yields of formic acid, oxalic acid, and other simple products.26 Ultraviolet light gives similar results. In these reactions, the Fe2+ is a stoichiometric reducing agent rather than a catalyst. Nitrogen in the form of N2 does not react, and experiments with NH3 have not been tried. 

A convenient two-step method for tetrahydropyran synthesis from tetrahydropyran-2-ones can be achieved by using a titanocene complex in the presence of a stoichiometric reducing agent, followed by treatment with Amberlyst 15 and triethylsilane <1998JOC2360>. 

Oshima s group reported the first example of a tandem radical cyclization/intermo-lecular Heck reaction in 2002 (Fig. 60) [289]. Iodoacetaldehyde allyl acetal 242a was treated with styrene 243, catalytic amounts of CoCl2(dpph), and trimethylsi-lylmethylmagnesium chloride 224 as a stoichiometric reducing agent. 4-Cinnamyl-butyrolactol 244 was isolated in 50% yield (cf. Fig. 54). 

In a more recent study Co(dppe)I2 was used as a catalyst for reductive additions of primary, secondary, and tertiary alkyl bromides or iodides 249 to alkyl acrylates, acrylonitrile, methyl vinyl ketone, or vinylsulfone 248 in an acetonitrile/water mixture using zinc as a stoichiometric reducing agent [305]. The yields of the resulting esters 252 were mostly good. The authors tested radical probes, such as cyclopropylmethyl bromide or 6-bromo-1-hexene (cf. Part 1, Fig. 8). However, the latter did not cyclize, but isomerized during addition, while the former afforded complicated mixtures. On this basis the authors proposed a traditional two-electron mechanism to be operative the results do not, however, exclude a radical-based Co(I) catalytic cycle convincingly (Fig. 61). 

Early examples of catalytic radical cyclizations were provided by Okabe and coworkers, who subjected 2-bromoethyl propargyl ethers or bromoacetaldehyde propargyl acetals 257 to complex 255 as a catalyst and sodium borohydride as the stoichiometric reducing agent (Fig. 63, Table 5, entry 1) [307, 308]. 

Reverse annulation reactions of bromoacetaldehyde cyclohexenyl acetals 261 catalyzed by 255 using NaBUt as the stoichiometric reducing agent provided bicycles 262 in 40-71% yield (Fig. 64, entry 5) [314, 315]. Cathodic reduction at — 1.8 V was also successfully applied to regenerate 255 or vitamin B12 247 in radical 5-exo cyclizations of 261 under optimized conditions (entry 6) [316, 317]. Less than 10% of the cyclic reduced products 263 were detected. 

More recently, van der Donk and coworkers reported radical cyclizations catalyzed by vitamin B12 using titanium(III) citrate as a stoichiometric reducing agent (Fig. 69, entry 17) [330]. Here /V-allylic 2-(isopropenyl) pyrroles 290 or allyl 2-phenylallyl ethers serve as the starting material in tandem hydrocobaltation/ radical 5-exo cyclization sequences giving dihydropyrrolizine derivatives 291 or 292. The mechanistic course is not completely clear. However, it is assumed that the reactions start with an initial hydrocobaltation of the isopropenyl unit in the presence of the allylic alkene (see Sect. 5.7). The benzylic cobalt intermediate is subject to homolysis of the very weak cobalt-carbon bond and initiates the radical 5-exo cyclization. Interestingly, the fate of the cyclized radical is dependent on the... 

Nadal and colleagues recently reported a Ni-catalyzed carbonylative Pauson-Khand-like [2+2+1] cycloaddition of allyl halides and alkynes in the presence of carbon monoxide and iron as the stoichiometric reducing agent [148]. The reaction was proposed to occur via reductively generated Ni(I)-radical like species free radicals were, however, considered unlikely. 

The Takai-Utimoto reaction of alkyl halides 360 with aldehydes 361 is a convenient method for the synthesis of branched alcohols 363 with high functional group tolerance [455]. Vitamin B12 362 or cobalt phthalocyanine served as the catalyst and CrCl2 as the stoichiometric reducing agent (Fig. 99). The reactions proceeded well with aromatic and aliphatic aldehydes. 

Corey originally used borane-THF as a stoichiometric reducing agent [2, 5]. The use of more robust borane sources, borane-N,N-diethylaniline [6, 7] and borane-N-ethyl-N-isopropylaniline [8, 9], rendered the CBS reduction easier to handle without sacrificing enantioselectivity. Borane-THF prepared in situ from NaBH4 and (CHalaSiCl in THF [10] was also shown to be useful for this type of reduction [11]. 

In this case, the silylation of the metal alkoxide initially formed represents the key step of the overall process which releases the chromium salt from the organic product. The other crucial parameter is the use of the stoichiometric reducing agent for the regeneration of the active Cr" species. Commercial Mn turned out to be particularly well suited, as it is very cheap, its salts are essentially non-toxic and rather weak Lewis acids, and the electrochemical data suggest that it will form an efficient redox couple with Cr . Moreover, the very low propensity of commercial Mn to insert on its own into organic halides guarantees that the system does not deviate from the desired chemo- and diastereoselective chromium path. Thus, a mixture of CrX ( = 2, 3) cat., TMSCl and Mn accounts for the first Nozaki reactions catalytic in chromium [13]. 

With respect to the stoichiometric reducing agent, manganese is more effective than is zinc in these chromium-catalyzed couplings. In the absence of a chromi-um(II) catalyst, pinacol coupling by manganese/Me3SiCl proceeds rather slowly. 

Gansauer was able to apply this new catalytic process to the pinacol coupling of a variety of aromatic aldehydes in excellent yield and diastereoselectivity (Eq. 3.41). Other metals (e.g., zinc, magnesium, and aluminum) were inferior to manganese as the stoichiometric reducing agent. 

Polymer-supported chiral oxazoborolidines have also been used for the reduction of prochiral ketones. Enantiomeric excesses of 98% were obtained for the reduction of acetophenone using borane dimethyl sulfide as a stoichiometric reducing agent [77, 78]. 

Trichlorosilane, a nonexpensive stoichiometric reducing agent, is relatively easy to handle under anhydrous (but not necessarily anaerobic) conditions. The aqueous workup produces NaCl and SiO2, two benign inorganics, which in conjunction with the use of toluene as the optimal solvent render this method environmentally acceptable. 

The yields and the ee values were significantly higher in the biocatalytic processes. Nevertheless, the chemical reductions needed substantially lower amounts of substrates because only hydrogen was used as a stoichiometric reducing agent and no buffer was necessary. 

The overall process involves a stoichiometric reducing agent which is plain old NaBH4 and another boron species Et2BOMe. We shall see in a minute that it is the job of this second boron species to hold the P-hydroxy ketone 156 in a ring as the reduction proceeds.39... 

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