Aldol-type reactions with aldehydes

A study of the kinetics and products of the thermolysis of a series of diaryl-phosphinic azides has been reported.119 Diethyl 1-diazomethylphosphonates undergo an aldol-type reaction with aldehydes to give l-diazo-2-hydroxyalkylphosphonates (152).120 Acidification of the diazophosphonates (153) possessing a chiral phosphorus centre yields mixtures of diastereoisomers (154) and epimers at C. For given R1 and R2, the reaction becomes increasingly stereoselective for X= OAc < Cl < OTs. It may be argued that protonation of (153) will yield a mixture of diastereoisomeric di-... 

In contrast to titanium enolates of ketones, titanium enolates of aldehydes exhibit practically no stereoselectivity in aldol reactions. However, titanation of dimethylhy-drazones of aldehydes with 1 results in substrates (2) that show high eryt/iro-selecti v i ty in aldol-type reactions with aldehydes (equation I). Bromotitanium tris(diethylamide) can be used in place of 1, but is less efficient, as is Ti(IV) isopropoxide.6... 

Hydroxy acetamides. The (R)-sulfinyljcetamidcs (2) obtained by reaction of the enolate of N,N-dialkylacetamides with 1 undergo an aldol-type reaction with aldehydes in the presence of base. The adducts (3) arc desulfurized to optically active P-hydroxy... 

Sulfonyl carbanions undergo aldol-type reactions with aldehydes and ketones to give p-hydroxy sulfones which can be converted into alkenes (the Julia reaction) (see Chapter 10, p. 197). With allyl methyl sulfones (75) and a,p-unsaturated carbonyl compounds (63),... 

Reaction With Carbonyl Compounds. Primary and secondary nitroparaffins undergo aldol-type reactions with a variety of aldehydes and ketones to give nitro alcohols (11). Those derived from the lower nitroparaffins and formaldehyde are available commercially (see Nitro alcohols). Nitro alcohols can be reduced to the corresponding amino alcohols (see Alkanolamines). 

Chiral bis-phosphine acylplatinum complex 210 with a strong acid such as TfOH serves as an effective enantio-selective catalyst for aldol-type reactions of aldehydes with ketene silyl acetals (Equation (127)).486 The presence of water and oxygen in the catalyst preparation step is required to obtain the highly enantioselective catalyst. The intermediacy of a C-bound platinum enolate was suggested by IR and 31P NMR spectroscopies. 

By 1989 Mukaiyama had already explored the behaviour of phosphonium salts as Lewis acid catalysts. It was possible to show that the aldol-type reaction of aldehydes or acetals with several nucleophiles and the Michael reaction of a,j3-unsatu-rated ketones or acetals with silyl nucleophiles gave the products in good yields with a phosphonium salt catalyst [116]. In addition, the same group applied bisphosphonium salts as shown in Scheme 45 in the synthesis of ]3-aminoesters [117]. High yields up to 98% were obtained in the reaction of A-benzylideneaniline and the ketene silyl acetal of methyl isobutyrate. Various analogues of the reaction parteers gave similar results. The bisphosphonium salt was found to be superior to Lewis acids like TiCl and SnCl, which are deactivated by the resulting amines. 

Methyl-2-alkenenitrttes (3).1 The aldol-type reaction of aldehydes with the ke-tenimine 1 catalyzed by MgBr2 or BF3 etherate is nonstereoselective. However, use of a catalyst composed of TiCl4 and Ti[OCH(CH3)2]4 in the ratio 1 3 results into a stereocon-trolled reaction to give 2, which is converted into 3 by treatment with BF3 etherate. 

Nitroalkanes having an a-hydrogen atom undergo aldol-type condensation with aldehydes and ketones in the presence of a base to give p-hydroxy nitro compounds or nitroethylene compounds. The reaction is known as the Henry reaction " or nitroaldol reaction. 

The original methods for directed aldol and aldol-type reactions of aldehydes and acetals with silyl enolates required a stoichiometric amount of a Lewis acid such as TiCh, Bl i-OI y, or SnCl.j [18]. Later studies have introduced many Lewis acids which accelerate these processes with a catalytic quantity (vide infra). In addition, it has been found that fluoride ion sources also work as effective catalysts of the aldol reaction [19]. In the last decade, much attention has been paid for the development of diastereo- and enantioselective aldol reactions [20, 21], aqueous aldol reactions using water-stable Lewis acids [22], and novel types of silyl enolate with unique reactivity. 

SbF6)2 [61], and an oxovanadium(IV) complex [62] are effective catalysts. Matsuda et al. recenfly reported that a cationic Ir complex generated in situ from [Ir(COD) (PPh3)2]OTf and H2 catalyzes aldol and aldol-type reactions of aldehydes and acetals with silyl enolates in CH2CI2 [63]. 

Loh, T.-P. and Li, X.-R., Clay montmorillonite KIO catalyzed aldol type reaction of aldehydes with silyl enol ethers in water. Tetrahedron, 1999, 55,10789 10802. 

Aromatic A-TMS-ketene imines undergo efficient aldol-type reaction with O-protected a-hydroxy aldehydes, giving iy -selectivity at ambient temperature, reversing at -78 °C to anti- Transfer of the TMS group from the ketene imine prevents (g) retro-reaction. 

Table 15.5 Aldol-type reaction of aldehydes 1 with silyl ketenes 92a (R = H, = Me), catalyzed by 81 (Scheme 15.18) [83].

Table 15.7 Aldol -type reaction of aldehydes 1 with vinylogous silyl ketenes 94a/94b ...

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

Formaldehyde condenses with itself in an aldol-type reaction to yield lower hydroxy aldehydes, hydroxy ketones, and other hydroxy compounds the reaction is autocatalytic and is favored by alkaline conditions. Condensation with various compounds gives methylol (—CH2OH) and methylene (=CH2) derivatives. The former are usually produced under alkaline or neutral conditions, the latter under acidic conditions or in the vapor phase. In the presence of alkahes, aldehydes and ketones containing a-hydrogen atoms undergo aldol reactions with formaldehyde to form mono- and polymethylol derivatives. Acetaldehyde and 4 moles of formaldehyde give pentaerythritol (PE) ... 

In Section 3.5 on alkene isomerization, it was mentioned that Li and co-workers reported a RuCl2(PPh3)3-catalyzed shuffling of functional groups of allylic alcohols in water (Eq. 3.35).140 Since the reaction proceeds through an enol intermediate, allyl alcohols can thus be considered as enol equivalents.203 This has been developed into an aldol-type reaction by reacting allyl alcohols with aldehyde (Scheme 3.11).204 The presence of In(OAc)3 promoted the aldol reaction with a-vinylbenzyl alcohol and aldehyde.205... 

---