Addition of benzaldehyde

Aldol additions of benzaldehyde with active methylene groups produce other aldehydes. 

Darzens reaction can be used to efficiently complete the stereoselective synthesis of a"-substituted epoxy ketones. As an example, Enders and Hett reported a technique for the asymmetric synthesis of a"-silylated a,P-epoxy ketones. Thus, optically active a -silyl a-bromoketone 38 was treated with LDA followed by the addition of benzaldehyde to give a"-silyl epoxyketone 40 in 66% yield with good... 

A variety of 1,3-oxazolidines have been used as chiral formyl anion equivalents for addition to aldehydes. Thus, for example, reaction of N-protected norephedrine with Bu3Sn-CH(OEt)2 gives 48, and transmetallation with BuLi followed by addition of benzaldehyde affords the expected adduct 49. The selectivity at the newly formed alcohol center is poor, but the situation can be salvaged by oxidation and re-reduction, which affords the product 50 with >95% d.e. It is then a simple matter to hydrolyze off the oxazolidine, although the resulting hydroxyaldehydes... 

The foregoing examples do not represent useful chiral formyl anion equivalents in a direct sense since the stereoselectivity of the initial addition to aldehydes is poor, although as has been explained, the situation is salvaged by oxidation and re-reduction. On the other hand, by lithiation at the 2 position of the achiral oxazo-lidine 53 in the presence of (-)-sparteine followed by addition of benzaldehyde, useful levels of d.e. and e.e. are achieved directly (98TA3125). For example, by adding MgBr2 before the benzaldehyde, the major product obtained is 54 in 80% d.e. and 86% e.e. 

Process economics dictate the recycling of the unwanted isomer. Path A in Figure A8.2 illustrates that racemisation of the D-N-benzylidene amino add amide is fadle and can be carried out under very mild reaction conditions. After removal of die benzaldehyde die D,L-amino add amide can be recyded 100% conversion to the L-amino add is theoretically possible. Another method for racemisation and recycling of the L-amino add (path B, Figure A8.2) comprises the conversion of the L-amino add into die ester in the presence of concentrated add, followed by addition of ammonia, resulting in the formation of the amide. Addition of benzaldehyde and racemisation by OH- (pH =13) gives the D,L-amino add amide. In this way 100% conversion to die D-amino add is possible. 

Double metalation of the protected (2/ .3S)-4-nitro-l, 2,3-butanetriol 4 and addition of benzaldehyde furnished, after removal of the protecting groups, a single crystalline diastereomer. The absolute configuration of the newly formed asymmetric carbons is assumed to be cither (4R,5S) or (4S,5R)ls. 

Evans Jr. and coworkers reported a similar olefination reaction employing spirooxyphosphoranes of type 66. Upon treatment with a strong base (LiHMDS) and subsequent addition of benzaldehyde, the reaction proceeded to form anionic P(VI) intermediates (67,6 -106 to -116 ppm) that decomposed at room temperature to form the corresponding olefins and spiropentaoxyphosphoranes [ 105]. The stereoselectivity (E Z ratio) of the double bond-forming reaction depended upon the conditions evidence indicated the possibility of kinetic or thermodynamic control (Scheme 21). 

Figure 2.P25 shows the calculated [B3LYP/6-31G(4,/f)] reaction energy profile for the aldol addition of benzaldehyde and cyclohexanone catalyzed by alanine. The best TSs leading to (S,R) (R,S) (S,S) and (R,R) products are given. What factors favor the observed (R,S) product ... 

The early addition of Dimedon is reported234 to depress the formation of hexamethylenetetramine from formaldehyde in the presence of ammonia. O Dea282 found that the activated methylene center, sometimes formed in periodate oxidations of carbohydrates, reacts appreciably with the formaldehyde formed, thus giving low yields of apparent formaldehyde. He was able to depress this side reaction by the use of lowered temperatures and by the addition of benzaldehyde or of p-hydroxybenzaldehyde. The analyses for formaldehyde have often been more successful at a pH of 7.5 than at lower pH values.57, 68 59a 60 264... 

There is an equilibrium between the dimer and monomer, and molecular orbital study suggests that the heterochiral dimer is more stable than the homochiral isomer. The existence and behavior of the dimeric species were well confirmed by experiments such as cryoscopic molecular weight and NMR measurement. In the NMR study of a DAIB-catalyzed dialkylzinc addition reaction, noticeable changes were observed in the spectrum of the homochiral dimer on the addition of benzaldehyde, while the spectrum of the heterochiral complex remained the same. This may imply that the heterochiral complex is very stable and does not react, and the homochiral dimer leads to the reaction product. 

Table 9.37 Addition of benzaldehyde dimethyl acetal to allenylsilanes.

Synthesis of homopropargylic alcohols To a solution of telluroallene (1.0 mmol) in THF (12 mL) under N2 at -78°C, n-BuLi (1.1 mmol) was added at once, followed by the immediate addition of benzaldehyde (1.0 mmol). The reaction was stirred for 1.5 h (monitored by TLC using hexane/AcOEt - 8 2). A saturated solution of NH4CI (3 mL) was added still at -78°C and then the reaction mixture was allowed to reach room temperature. After normal work-up the product was purified by flash chromatography using a mixture of hexane/ethyl acetate (8 2) as eluent. 

Heating organomercurial 34 resulted in the a-ehmination of phenyl mercury bromide, generating dichlorocarbene, followed by addition of benzaldehyde to form the corresponding carbonyl ylide 35. This ylide can be intercepted with dimethyl-acetylene dicarboxylate (DMAD) to produce dihydrofuran (36), which formed furan 37 through a dehydrochlorination process in 46% yield. 

As shown in Eqs. (17) and (18), the isolated formyls 19 and 24 are capable of reducing aldehydes and ketones (37, 38, 42. 47, 66). Thus there is no doubt that hydride transfer is an intrinsic chemical property of anionic formyl complexes. One reaction of a neutral formyl complex with an aldehyde has been reported addition of benzaldehyde to (i7-C5H5)Re(NO)(CO)(CHO) (38) yields the alkoxycarbonyl complex (i7-C5H5)Re(NO)(CO)(C02CH2C6Hs) (62). This transformation, which appears to require catalysis by adventitious acid, can be viewed as occurring via attack of initially formed benzyl alcohol upon the intermediate carbonyl cation [(i -C5H5)Re(NO)(CO)2]+. 

A rationalization for the formation of 10 is presented in Scheme 4. The crucial feature is that lithiation of the oxide 7 occurs at two different sites, in both of which internal coordination to lithium is important. When lithiation occurs on the 6-carbon, giving 13, formation of the dienylphosphine oxide 11 results, and hence anion 12 arises. Upon quenching with water the dimeric dioxide 10 is formed. In a separate experiment, addition of benzaldehyde led to isolation of a trienylphosphine oxide whose formation we take to be further evidence for the anion 12. 0... 

Reductive dehalogenation of fi-halo ketones.1 a-Bromo or a-chloro ketones undergo reductive dehalogenation on reaction with freshly prepared A1I3 in refluxing CH3CN (80-95% yield). The reaction probably involves an aluminum enolate since addition of benzaldehyde results in an aldol condensation. 

More recently, Bradley has demonstrated the chemoselective capture of primary amines over secondary amines using a polymeric methacrylate (AAEM) 13 as a purification method for an in-situ reductive amination procedure (Scheme 5) [13]. Reduction of the imines 17a-c (formed by addition of benzaldehyde 15 to an excess of the primary amines 16a-c) gave the required secondary amines 18a-c. The remaining unwanted primary amines 16a-c was chemoselectively removed by the addition of the scavenger resin, acetoacetoxy ethyl methacrylate (AAEM) 13 to give the enamines 19a-c. Simple filtration of the reaction mixture gave the required secondary amine in good yield and excellent purity. Previously, within this area benzaldehyde-based resins (like 14) have been used, but were problematic, as they were particularly air sensitive. 

The presence of formaldehyde in the eleptrolytic reduction of nitro-compounds produces an effect entirely different from that caused by the addition of benzaldehyde. The phenomena occurring in this case have been thoroughly investigated by Lob.2... 

More recent evidence from our laboratory indicates that when the thiazolium salt is first converted totally to the unsymmetrical and symmetrical syn-anti dimers (13C NMR indicated the presence of both configurations), addition of benzaldehyde to this solution cannot form HBT, whereas addition of benzaldehyde to a mixture that still contains monomeric thiazolium salts indeed forms this HBT adduct57. Such experiments tend to confirm that it is the enamine rather than the double enamine (the benzaldehyde adduct of the syn-anti dimers) that participates in thiazolium salt catalyzed benzoin condensations. 

Enolates can also be prepared by rhodinm-catalyzed isomerization of allylic Uthinm alcoholates, such as 14 (equation 5)". Subsequent treatment of the intermediately formed rhodium hydride complexes (15 and 16) with an electrophile led to the formation of various products. For example, alkyl halides gave a-alkylated ketones (17) in good yields, as shown in Table 4. Interestingly, addition of benzaldehyde under kinetically controlled... 

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