Aldehydes Initial Studies

Although there is evidence that quaternary ammonium salts are cleaved by sodium borohydride at high temperature [7], initial studies suggested that the quaternary ammonium borohydrides might have some synthetic value in their selectivity, e.g. aldehydes are reduced by an excess of the quaternary ammonium salts under homogeneous conditions in benzene at 25 °C, whereas ketones are recovered unchanged and are only partially reduced at 65 °C [2], The reduction of esters also requires the elevated temperature, whereas nitriles are not reduced even after prolonged reaction at 65 °C. Evidence that the two-phase (benzene water) reduction of octan-2-one by sodium borohydride was some 20-30 times faster in the presence of Aliquat, than in the absence of the catalyst [8], established the potential use of the mote lipophilic catalysts. 

The material reviewed in this Chapter hitherto has focused on metallacarboranes in which the metal atom is a vertex in an icosahedral cage framework. Until recently, monocarbollide metal compounds with core structures other than 12 vertexes were very rare since suitable carborane precursors were not readily available." However, Brellochs recent development of the reaction of decaborane with aldehydes to give 10-vertex monocarboranes permits a considerable expansion in this area of boron cluster chemistry. As a consequence, several intermediate-sized monocarboranes are now easily accessible and we have recently begun to exploit the opportunities that these present. In particular, we have focused thus far on complexes derived from the C-phenyl-substituted species [6-Ph- zJo-6-CBgHii] It is clear from these initial studies that a wealth of new chemistry remains to be discovered in this area, not only from among the metal derivatives of PhCBg car-boranes such as those discussed in this section, but also in the metal complexes of other newly available carboranes. 

Since the initial studies, the substrate scope has expanded to include heteroatom-substituted ketones [208-216], cyclic ketones [217] and aldehydes [211, 218-226] as donors, and formaldehyde-derived imines [218, 227-232] as well as glyoxylate-derived imines [96, 220, 233-237] as acceptors. In addition, several alternative catalysts to proline have been pursued [238-242]. 

The initial study on the MeO-TEMPO / Mg(N03)2 / NBS triple catalyst system in the oxidation of 1 indicated the necessity of all three components the TEMPO based catalyst, the nitrate source (MNT) and the bromine source (NBS). A large number of metal nitrates and nitrites were screened initially and the highest activity and aldehyde selectivity under comparable reaction conditions were recorded using Mg(N03)2 as the nitrate component. A number of organic and inorganic bromides soluble in HOAc were also screened and high reaction rates were found when NBS was used as the bromide source. The effect of the concentration of the individual components of the new triple catalyst system on the reaction rate, on the conversion of 1 and on the selectivity to 2 over 60 min reaction time is shown in Figure 1. 

Initial studies showed that the encapsulated palladium catalyst based on the assembly outperformed its non-encapsulated analogue by far in the Heck coupling of iodobenzene with styrene [7]. This was attributed to the fact that the active species consist of a monophosphine-palladium complex. The product distribution was not changed by encapsulation of the catalyst. A similar rate enhancement was observed in the rhodium-catalyzed hydroformylation of 1-octene (Scheme 8.1). At room temperature, the catalyst was 10 times more active. For this reaction a completely different product distribution was observed. The encapsulated rhodium catalyst formed preferentially the branched aldehyde (L/B ratio 0.6), whereas usually the linear aldehyde is formed as the main product (L/B > 2 in control experiments). These effects are partly attributed to geometry around the metal complex monophosphine coordinated rhodium complexes are the active species, which was also confirmed by high-pressure IR and NMR techniques. 

Nagasawa and co-workers reported the use of a chiral bis-thiourea catalyst (108) for the asymmetric MBH reactions of cyclohexenone with aldehydes [95]. Since others had already shown that thioureas form hydrogen bonds with both aldehydes and enones, it was hypothesized that the inclusion of two thiourea moieties in close proximity on a chiral scaffold would organize the two partners of the MBH reaction and lead to enantiofacial selectivity. Initial studies showed that the achiral 3,5-bis-(trifluoromethyl)phenyl-substituted urea increased the rate of MBH reaction between benzaldehyde and cyclohexenone. These authors then showed that chiral 1,2-cyclohexyldiamine-linked bis-thiourea catalyst 108, used at 40 mol% loading in the presence of 40 mol% DMAP, promoted the MBH reactions of cyclohexenone with various aliphatic and aromatic aldehydes (40) to produce allylic alcohols in moderate to high yields (33-99%) and variable enantio-selectivities (19-90% ee Table 6.33). 

The phenoxazine-based ligand Nixantphos 8, which was derived from van Leeuwen s initial studies of xanthene-based diphosphine ligands [36], was used as the catalyst in a hydroformylation reaction as well. Nixantphos 8 proved to be a superior ligand with regard to its selectivity towards the linear aldehyde [37]. Moreover, Nixantphos 8 has recently been successfully immobilized on a silica 9 [38-40] and polystyrene 10 [41] matrix. After metal complexation, a catalyst can be obtained that is suitable for recycling by simple filtration (Fig. 4). 

Five months later, Corey and Lee reported the enantioselective Diels-Alder reaction between cyclopentadiene and a,/ -acetylenic aldehydes catalyzed by a chiral cationic oxazaborinane catalyst [33]. Although initial studies of the Diels-Alder reaction between cyclopentadiene and 2-butyn-l-al or 2-octyn-l-al with 20 mol % catalyst at -94 °C to -78 °C revealed only 3-5 % conversion to product over a 24-h period, replacement of the /3-alkyl substituent on the aldehyde component by RsSi or RsSn groups resulted in much faster Diels-Alder addition (Eq. 33). The greater yield with 3-tributylstannyl-2-propyn-l-al, compared with the 3-silyl analogs, results from the rate of reaction with the former. In each instance, good enantioselectivity (80-87 % ee) was obtained. 

Both a- and y-oxygenated allylic stannanes add to aldehydes under thermal or Lewis-acid-promoted conditions. These reagents are less reactive and more acid-labile than their non-oxygenated counterparts. Consequently, the best results are obtained with relatively reactive aldehydes. Strong Lewis acids cannot be used because they tend to cause decomposition of the stannanes. Initial studies employed thermal conditions to effect the additions. Thus, the frans-a-OMOM crotylstannane, prepared from crotonaldehyde by addition of BuaSnLi and etherification of the alcohol adduct, afforded the anti-(Z) adduct upon treatment with benzaldehyde under reflux in toluene (Eq. 28) [46]. 

In addition to chloral the polymerization of other chlorinated aldehydes was studied by Kambe et al., for example that of oi-chloro iso-butyraldehyde. It was also found in this case that the initiation was almost instantaneous and the growing polymer ends could be acetylated when acetylation was carried out immediately at the low polymerization... 

The reaction of a silylacetate derivative with an aldehyde or ketone was initially studied by Rathke and Yamamoto. Rathke and coworicers studied the addition of the lithium anion of r-butyl (trimethylsi-lyl)acetate (340) with a variety of aldehydes and ketones (equation 78). The anion can be formed directly from the silyl compound on treatment with LDA. The reaction proceeded to give the conjugated alkenes in excellent yields. Unsaturated compounds reacted via 1,2-addition. No discussion of alkene geometry was present. In the Yamamoto work, the ethyl (trimethylsilyl)acetate derivative (342) was used in a variety of reactions with aldehydes and ketones (equation 79). The anion was formed wiA dicyclohexyl-amide in THF. It was stated in the experimental section that the ( ) (Z) ratios of alkenes were dependent on the reaction conditions. In all the examples presented in this work, the ( )-isomer was predominantly formed. 

NA hen Harries (2) at the beginning of the present century carried out his fundamental experiments with a view to ozonizing organic compounds, he also studied the effect of ozone on certain sugar alcohols. His initial studies showed that the primary alcoholic hydroxyls of sugar derivatives can be oxidized to form aldehyde groups by utilizing ozone. 

A highly anti-selective hydrocyanation of (7 )-jV-Boc-2, 2-dimethylthia-zolidine-4-carbaldehyde (Gamer s aldehyde) with hydrogen cyanide in the presence of a Lewis acid has been reported [78]. In the initial study, we applied the procedure to the synthesis of anti-O-TMS cyanohydrin 23. However, the cyanosilylation of 22 in the presence of Lewis acid such as zinc iodide (Znl2), zinc bromide (ZnBr2) or boron trifluoride (BFy) diethyl ethcrate was problematic, leading only to traces of 23. 

The first example of the Lewis acid-catalyzed asymmetric addition of achiral allylstannanes to achiral aldehydes was reported by Marshall in 1992 using Yamamoto s chiral (acyloxy)borane (CAB) catalyst [87]. In initial studies with this catalyst, both aliphatic and aromatic aldehydes could be employed with substituted... 

Keck [89a-c], Tagliavini [89d,e], and Yu [89f] have extensively studied the BINOL-Ti- or binol-Zr promoted reactions of achiral aldehydes with allylstan-nanes. The initial studies employed BINOL and either Ti(Oi-Pr)4 or TiCl2(0/-Pr)2 as the Lewis acid promoter in the reaction of achiral aldehydes with allyltributyl-stannane. The reaction affords good yields of the desired homoallylic alcohol with a high degree of enantioselectivity even with as little as 10 mol% of the chiral catalyst (Scheme 10-49) [89a]. The rate and turnover of the catalytic, asymmetric allylation reaction have also been optimized. It was found that when /-PrSSiMe3 is added to the reaction, a rate acceleration occurs, allowing as little as 1-2% of the catalyst to be used [89 fj. 

Sinha et al. [7] for the first time reported a highly efficient and recyclable combination of Candida antarctica lipase B (CAL-B) and nentral ionic liqnid [hmim] [Br] for metal-free activation in the chemoselective oxidation of aryl alcohols. Initial study was carried out using 4-methoxyphenyl propanol, as substrate, and HjOj at 40°C in the presence of CAL-B/[hmim][Br], thereby providing aldehyde in 90% yield after 16 h. Increasing the reaction temperature to 60°C significantly brought down the reaction time from 16 to 8 h (Scheme 14.7). 

The initial studies on the reaction of enol silanes and aldehydes implicated the stoichiometric metal promoter, such as TiCl4, as a Lewis acid. Subsequent investigations confirmed this hypothesis, ruling out a reaction between ketone- or ester-derived enol silane and TiCl4 under the typical conditions employed for... 

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