Ethers reductive -elimination

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

Remarkable solvent effects on the selective bond cleavage are observed in the reductive elimination of cis-stilbene episulfone by complex metal hydrides. When diethyl ether or [bis(2-methoxyethyl)]ether is used as the solvent, dibenzyl sulfone is formed along with cis-stilbene. However, no dibenzyl sulfone is produced when cis-stilbene episulfone is treated with lithium aluminum hydride in tetrahydrofuran at room temperature (equation 42). Elimination of phenylsulfonyl group by tri-n-butyltin hydride proceeds by a radical chain mechanism (equations 43 and 44). 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

Recently, Akiyama et al. reported an enantiocontrolled [3+2] cycloaddition of chirally modified Fischer alkenylcarbene complexes 180 with aldimines 181 under Lewis-acid catalysis (Sn(OTf)2) to afford enantiomerically pure 1,2,5-trisubstituted 3-alkoxypyrrolines 182 (Scheme 40) [121]. The mode of formation of these products 182 was proposed to be a [4+2] cycloaddition, with the complexes 180 acting as a 1-metalla- 1,3-diene with subsequent reductive elimination. Upon hydrolysis under acidic conditions, the enol ethers give the enantiomerically pure 3-pyrrolidinones 183 (Table 9). 

This procedure illustrates a general method for the stereoselective synthesis of ( P)-disubstitnted alkenyl alcohols. The reductive elimination of cyclic /3-halo-ethers with metals was first introduced by Paul3 and one example, the conversion of tetrahydrofurfuryl chloride [2-(chloromethyl)tetrahydrofuran] to 4-penten-l-ol, is described in an earlier volume of this series.4 In 1947 Paul and Riobe5 prepared 4-nonen-l-ol by this method, and the general method has subsequently been applied to obtain alkenyl alcohols with other substitution patterns.2,6-8 (I )-4-Hexen-l-ol has been prepared by this method9 and in lower yield by an analogous reaction with 3-bromo-2-methyltetra-hydropyran.10... 

The bipyridyl ligand, with 80 %, gives the best catalyst, probably because it affords the best balance between the a-donor and rt-acceptor characters which favours respectively the oxidative addition of the aryl bromide and the reductive elimination of the aryl ether at the nickel center. 

This reaction sequence of conjugate reduction followed by aldol reaction is known as the reductive aldol reaction. In certain instances, reductive elimination from the M-TM-enolate species may occur to furnish M-enolate, which itself may participate in the aldol reaction (Scheme 3). This detour may be described as the background path or stepwise path in one-pot. Indeed, it has been reported that certain cationic Rh complexes such as [Rh(COD)(DPPB)] (COD = 1,5-cyclooctadiene, DPPB = diphenylphosphinobutane) catalyze the aldol reactions of silyl enol ethers and carbonyl compounds by serving as Lewis acids [5-8]. 

More recently, reductive elimination of aryl ethers has been reported from complexes that lack the activating substituent on the palladium-bound aryl group (Equation (55)). These complexes contain sterically hindered phosphine ligands, and these results demonstrate how steric effects of the dative ligand can overcome the electronic constraints of the reaction.112,113 Reductive elimination of oxygen heterocycles upon oxidation of nickel oxametallacycles has also been reported, but yields of the organic product were lower than they were for oxidatively induced reductive eliminations of alkylamines from nickel(II) mentioned above 215-217... 

Like alkynes, a variety of mechanistic motifs are available for the transition metal-mediated etherification of alkenes. These reactions are typically initiated by the attack of an oxygen nucleophile onto an 72-metalloalkene that leads to the formation of a metal species. As described in the preceding section, the G-O bond formation event can be accompanied by a wide range of termination processes, such as fl-H elimination, carbonylation, insertion into another 7r-bond, protonolysis, or reductive elimination, thus giving rise to various ether linkages. 

In addition to /3-H elimination, olefin insertion, and protonolysis, the cr-metal intermediate has also proved to be capable of undergoing a reductive elimination to bring about an alkylative alkoxylation. Under Pd catalysis, the reaction of 4-alkenols with aryl halides affords aryl-substituted THF rings instead of the aryl ethers that would be produced by a simple cross-coupling mechanism (Equation (126)).452 It has been suggested that G-O bond formation occurs in this case by yy/z-insertion of a coordinated alcohol rather than anti-attack onto a 7r-alkene complex.453... 

Further insight into the carbon-oxygen reductive elimination from Pt(IV) and the involvement of five-coordinate Pt(IV) intermediates has been provided recently. The first direct observation of high-yield C-0 reductive elimination from Pt(IV) was described and studied in detail (50,51). Carbon-oxygen coupling to form methyl carboxylates and methyl aryl ethers was observed upon thermolysis of the Pt(IV) complexes ( P2 )PtMe3(OR) ( P2 =bis(diphenylphosphino)ethane or o-bis(diphenyl-phosphino)benzene OR=carboxylate, aryl oxide). As shown in Scheme 47, competitive C-C reductive elimination to form ethane was also observed. 

In comparison to the N- and S-counterparts, alkoxides possess lower nucleophilicity. Therefore, the reductive elimination process to form the C—O bond is much slower than those to form C— N and C—S bonds [103]. Palucki, Wolfe and Buchwald developed the first intramolecular Pd-catalyzed synthesis of cyclic aryl ethers from o-haloaryl-substituted alcohols [104]. For example, 3-(2-bromophenyl)-2-methyl-2-butanol (91) was converted to 2,2-dimethylchroman (92) under the agency of catalytic Pd(OAc)2 in the presence (S)-(-)-2,2 -bis(di-p-tolylphosphino)-l,r-binaphthyl (Tol-BINAP) as the ligand and K2CO3 as the base. The method worked well for the tertiary alcohols, moderately weE for cychc secondary alcohols, but not for acyclic secondary alcohols. 

Reductive elimination of an allylic diol group. A new synthesis of vitamin A involves reduction of the allylic diol 1, prepared in several steps from JJ-ionone, with a low valent titanium formed from TiCl3 and LiAlH, in the ratio 2 1. Thus, the allylic diol group of 1 [either (E) or (Z)] is reduced to an (E,E)-1,3-diene group to form the silyl ether (2) of vitamin A.1 When the primary hydroxyl group is protected as an acetate, the reduction gives a mixture of (E)- and (Z)-2. 

On the other hand, the use of [Rh(CO)2Cl]2 as a catalyst results in ring opening of the siloxycyclopropanes 13 to the silyl enol ethers 14 with high stereoselectivity [10]. The 2-siloxyrhodacyclobutane 15a is proposed to undergo j8-elimination to give jr-allylrhodium 16a followed by reductive elimination to the silyl enol ether 14a. 1-Trimethylsiloxybicyclo[n.l.0]alkanes serve as / -metallo-carbonyl compounds via desilylation with a variety of transition metals [11]. The palladium-catalyzed reaction of the siloxycyclopropanes 17 under carbon monoxide in chloroform provides a route to the 4-keto pimelates 18. In the presence of aryl triflates, the 1,4-dicarbonyl compounds 19 are... 

A third approach to the preparation of allyl lluorovinyl ethers is the reaction of an allylic alcohol with trifluoroacetaldehyde, as illustrated by an alternative synthesis of 37a.17 Cinnamyl alcohol (47) forms with trifluoroacetaldehyde a hemiacetal, which is converted into bromide 48 via the mesy late. Reductive elimination affords 37a, which undergoes Claisen rearrangement within one hour in refluxing carbon tetrachloride to give 2,2-difluoro-3-phenylpent-4-enal (38a).17... 

The discovery of an easy route to a series of l-chloro-l-(trichlorovinyl)cyclopropanes from the thermal reaction of tetrachlorocyclopropene and olefins greatly promoted the availability and synthetic utility of alkynylcyclopropanes. Upon reductive elimination with two equivalents of n-BuLi in ether-hexane at -78 °C, a series of ring substituted... 

---