Benzylic boron, reaction with aldehydes

The approach for the enantioselective aldol reaction based on oxazolidinones like 22 and 23 is called Evans asymmetric aldol reaction.14 Conversion of an oxazolidinone amide into the corresponding lithium or boron enolates yields the Z-stereoisomers exclusively. Reaction of the Z-enolate 24 and the carbonyl compound 6 proceeds via the cyclic transition state 25, in which the oxazolidinone carbonyl oxygen and both ring oxygens have an anti conformation because of dipole interactions. The back of the enolate is shielded by the benzyl group thus the aldehyde forms the six-membered transition state 25 by approaching from the front with the larger carbonyl substituent in pseudoequatorial position. The... 

The synthesis began with Prins qrchzation of the symmetric vinylo-gous ester 273, prepared from heptadienol 272, followed by hydrolysis of the resulting trifluoroacetate and benzylation, to afford the desired 2,6-cis-tetrahydropyran 274 with 92 8 diastereoselection at C5 [113], By this novel desymmetrization, 2,4,6-all-ci5 trisubstituted pyran was efficiently provided. Boron-enolate aldol reaction, as Carreira did, of the methyl ketone 274 with aldehyde 275 gave hydroxy ketone 271 as a single isomer. In contrast to Car-reira s result, samarium-catalyzed intramolecular Tishchenko reduction [114]... 

The dioxaborole (97), formed from catecholborane and ethojqracetylene, undergoes a Pd-catalysed cross-coupling reaction with aryl or benzyl halides RX to give the vinyl ethers (98). Since these vinyl ethers can readily be hydrolysed to aldehydes (99), the overall sequence provides an efficient method for converting halides into aldehydes with two more carbon atoms. Also on the subject of boronic acid chemistry, a number of syntheses of the useful intermediates (100) have been published. ... 

The aldol reactions of (9-protected (R)- or (5)-hydroxyacetyl 4-substituted 1,3-oxazolidin-2-ones (0-protected chiral glycolates) show some peculiarities. The boron enolates of (S)-and (7 )-3-p-methoxybenzyloxyacetyl-4-benzyl-l,3-oxazolidin-2-one (2381 react with aldehydes to provide the expected syn aldols . In contrast, anti aldols are formed in high stereoselectivities with the corresponding stannous enolates when the reactions are run in the presence of TMEDA °. 

Treatment of 122 with (R,R)-tartrate crotyl-boronate (E.R.R)-W 1 provides the alcohol corresponding to 123 with 96% stereoselectivity. Benzylation of this alcohol yields 123 with 64% overall yield. The crude aldehyde intermediate obtained by ozonolysis of 123 is again treated with (Z,R,R)-111 (the second Roush reaction), and a 94 5 1 mixture of three diastereoisomers is produced, from which 124 can be isolated with 73% yield. A routine procedure completes the synthesis of compound 120, as shown in Scheme 3-44. Heating a toluene solution of 120 in a sealed tube at 145°C under argon for 7 hours provides the cyclization product 127. Subsequent debromination, deacylation, and Barton deoxygenation accomplishes the stereoselective synthesis of 121 (Scheme 3-44). 

For the synthesis of amino acids, the reaction of an a-haloalkyl boronic ester 4 with sodium azide and a phase-transfer catalyst in dichloromethane/water requires a large excess of azide in order to form the a-azidoalkyl boronic ester 5 with only 1-2% epimer34. With the exception of R1 = benzyl, where epimerization of 4 is relatively rapid, bromoalkyl boronic esters are preferred. Chloroalkyl boronic esters react so slowly that the azide and dichloromethane may generate hazardously explosive diazidomethane65,66. Chain extension of 5 to 6 proceeds normally. Sodium chlorite, which is known to oxidize aldehydes to carboxylic acids67-69, also oxidizes a-chloroalkyl boronic esters to carboxylic acids34. The azido acid is hydrogenated to the amino acid. 

In our synthesis, iterative aldol reactions of dipropionate reagent (R)-18 allowed for the control of the C3-C10 stereocenters (Scheme 9-72) [89]. Hence, a tin-mediated, syn aldol reaction followed by an anti reduction of the aldol product afforded 270. Diol protection, benzyl ether deprotection and subsequent oxidation gave aldehyde 271 which reacted with the ( )-boron enolate of ketone (/ )-18 to afford anti aldol adduct 272. While the ketone provides the major bias for this reaction, it is an example of a matched reaction based on Felkin induction from the... 

The three contiguous stereochemical centers of oleandrose (504), an important carbohydrate present in the avermectins, can be readily assembled in one step by the addition of a y-methoxyallyl boronate (500) to 464 [159] (Scheme 72). This key reaction gives triol derivative 501 along with two minor isomers in a ratio of 8.7 1.2 1. Separation of these isomers is possible at the alcohol stage (502). Oxidation of the alcohol 502 to aldehyde 503 followed by hydrogenolysis of the benzyl groups gives 504 with 90% ee. 

The reaction of (281) with boron trifluoride-diethyl ether complex has been investigated it was known previously that the phenyl analogue undergoes fission of the benzylic C—O bond to give carbonium ions. In benzene or CHjClj (281) rapidly yielded cis-fluorohydrin (282) as the major (85%) product and the aldehyde (283). In contrast to benzene in which the product was stable, in CHjClj (282) was consumed after 1 h, yielding (283) and (284). In saturated aqueous CHjClj the essentially time-... 

---