Alcohols remote carbonylations

Attempts to achieve selective oxidations of hydrocarbons or other compounds when the desired site of attack is remote from an activating functional group are faced with several difficulties. With powerful transition-metal oxidants, the initial oxidation products are almost always more susceptible to oxidation than the starting material. When a hydrocarbon is oxidized, it is likely to be oxidized to a carboxylic acid, with chain cleavage by successive oxidation of alcohol and carbonyl intermediates. There are a few circumstances under which oxidations of hydrocarbons can be synthetically useful processes. One group involves catalytic industrial processes. Much effort has been expended on the development of selective catalytic oxidation processes and several have economic importance. We focus on several reactions that are used on a laboratory scale. 

Consistent with the direct observation of the emissions are field measurements in remote areas. For example, Fehsenfeld et al. (1992) measured the composition of VOC at two rural locations in the United States, summarized in Fig. 6.27. Alcohols and carbonyl compounds comprise 40-70% of the total. Of these, a significant portion appear to be direct emissions, with methanol being a major contributor to the oxygen-containing portion. Similarly, Singh et al. (1995) re-... 

A simultaneous reduction-oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (8) [33], This is an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, because of its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules, including natural and unnatural products. Thus, treatment of hydroxy aldehyde 18 with 8 (5 mol%) in CH2CI2 at 21 °C for 12 h resulted in formation of hydroxy ketone 19 in 78 % yield. As expected, the use of 25 mol% 8 enhanced the rate and the chemical yield was increased to 92 %. A similar tendency was observed with the cyclohexanone derivative. It should be noted that the present reduction-oxidation sequence is highly chemoselective, and can be utilized in the presence of other functionalities such as esters, amides, rert-alco-hols, nitriles and nitro compounds, as depicted in Sch. 10. 

A simultaneous reduction/oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (49). This represents an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, due to its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules including both natural... 

Carbonylation of saturated alcohols occurred to afford -lactones in moderate to good yields (Scheme 13.33) [56]. The mechanism of fhe remote carbonylation probably involves ... 

Remote carbonylation. Saturated alcohols form 5-lactones on reaction with Pb(OAc)4 and carbon monoxide. 

Lactone rings have also been constructed using carbonylation of appropriately functionalized compounds by the insertion of carbon monoxide. Ryu, Sonoda et al. have reported the synthesis of 8-lactones from saturated alcohols and carbon monoxide via remote carbonylation [110,111] (Scheme 64). Treatment of saturated alcohol 292 with lead tetraacetate led to oxygen-centered radical 293, which underwent a 1,5-hydrogen transfer reaction to produce carbon-centered radical 294. Trapping of this radical with carbon monoxide and oxidation followed by cyclization gave lactone 297. 

Maruoka reported the use of the didentate catalyst 8 for double electrophilic activation of carbonyl compounds [70], but since no comparison with monofunctional phenolates was given it is not clear whether having two aluminium centres in the same catalyst offers any special advantages. They used this catalyst to effect transfer hydrogenation between remote aldehyde and alcohol groups in the same molecule [71], but again it is not clear whether the transfer is truly intramolecular or in any way different from that of reduction by an external alcohol using 8 or a monuclear aluminium catalyst. 

The 1,4,5-oxadiazepine 63 was transformed into 65 by a four-step reaction sequence (1) cleavage of both /-butoxycarbonyl (BOC) and the lactone, (2) acylation of the remote amino group with 2-(trimethylsilyl)ethyloxy-carbonyl chloride (TeocCl), (3) protection of the alcohol functionality with a silyl group, and (4) ester hydrolysis (Scheme 10) C1998AGE2995, 2001CEJ41>. 

Each alcohol has a saturated carbon atom next to oxygen, all close together. Then there are carbons next door but one to oxygen they are back in the 0-50 p.p.m. region but at its low field end— about 30-35 p.p.m.. Notice the similarity of these chemical shifts to those of carbons next to a carbonyl group (Table 3.5 on p. 63). In each case we have C-C-O and the effects are about the same. Two of the alcohols have carbon(s) one further away still at yet smaller chemical shift (further upfield, more shielded) at about 20 p.p.m., but only the n-butanol has a more remote carbon still at 15.2. The number and the chemical shift of the signals identify the molecules very clearly. 

The sole exception of preferential endo attack is seen in the reaction of cuprates with oxanorbornenyl ketones [106]. The unusual and unprecedented endo delivery of the nucleophile is proposed to proceed via a prior complexation of the bridgehead oxygen with one equivalent of the cuprate on the less hindered side, followed by addition of another equivalent of cuprate from the more hindered endo face of the carbonyl group. Table 2 shows the reactions of 88 with various cuprates to give the exo alcohols (entries 1 -3). The remote olefin shows a positive effect in promoting endo nucleophilic attack, as shown by the reactions of 88 and 89 respectively (entry 1 vs. 4). 

Asymmetric carbonyl-ene reaction with l.2 The reaction of racemic allylic alcohols (2) with methyl glyoxalatc catalyzed by (R)-l can proceed with remote asymmetric-induction, which suggests that (R)-I can discriminate between the two cne components. 

The design and catalytic activity of dibenzobarrelene-based bifunctional PC(5p )P pincer catalysts for acceptor-less dehydrogenation of primary and secondary alcohols to give carbonylic and carboxylic compounds has been described. The mechanism of the H2 formation involves intra-molecular cooperation between the structurally remote functionality and the metal centre. The feasibility of the complete catalytic cycle was studied using a stoichiometric model. ... 

Spectra.—For compounds of low solubility in deuteriochloroform, the use of ASCI3-CDCI3 (2 1 v/v) may prove valuable as the chemical shift differences (excepting alcohols) between the two solvent systems is negligible (< 1 p.p.m.) on the n.m.r. scale. Titanium tetrachloride-induced shifts on the spectra of carbonyl compounds has been investigated. The carbonyl carbon atoms experience large down-field shifts, adjacent carbon atoms showed only small downfield shifts, and remote carbon atoms are scarcely perturbed. In a -unsaturated carbonyl compounds, large downfield shifts are observed for the P-carbon atoms, presumably because of the enhancement of the dipolar resonance form of the enone system consistent with this picture is the much smaller shift, in either direction, of the a-carbon atoms. Studies were extended to include ap-unsaturated acids and esters. ... 

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