Diastereoselectivity with Grignard reagents

Addition of alkynes to a-alkoxy aldehydes is most favorably performed with the corresponding zinc reagents (Table 12)46. As with Grignard reagents, the chelation-controlled addition of zinc alkynes proceeds with higher diastereoselectivity when diethyl ether rather than tetrahydrofuran is used as reaction solvent. 

Similar results are found with the threose derivatives 11 and 13. Both aldehydes can be readily synthesized in either enantiomeric form from l- and D-tartaric acid. The open-chain aldehyde 11 with Grignard reagents affords predominantly the all-.v> n(xj/o)-diastereomer 12. The steric demand of the nucleophile apparently does not affect the diastereoselectivity, and the extremely high selectivity observed with [(l,3-dioxolan-2-yl)methyl]magnesium bromide is attributed to the presence of the dioxolane moiety, which is thought to stabilize the a-chelated transition state. 

Chiral oxime ethers 229 of R)- and (5 )-0-(l-phenylbutyl)-hydroxylamine (ROPHy/ SOPHy) react with Grignard reagents in the presence of BFs OEta in toluene at —78°C yielding addition products with high diastereoselectivities (equation 154) . The resulting chiral hydroxylamine derivatives have been converted enantioselectively to primary amines, or (when R = allyl) to / -amino acids. 

Synthesis of A—protected (R)-3-alkylisoindolin-l-ones via diastereoselective reduc- (g) tive alkylation with Grignard reagent and triethylsilane has been reported. The emphasis is on the stereochemical outcome of the key diastereoselective reactions.318... 

Chiral a-carbamoyloxy-2-alkenylboronates react with Grignard reagents with complete a- and diastereoselectivity through rearrangement of an intermediate ate -complex, yielding chiral allylboronates, which were oxidized to... 

The method has been applied to the diastereoselective synthesis of naturally occurring compounds such as frontalin (84-100% ee) and(—)-malyngolide (95% ee). On the other hand, diastereoselective alkylation of chiral formylaminal with Grignard reagents and the subsequent hydrolysis afford optically active S-a-hydroxyaldehydes with moderate stereoselectivity (60% ee). ... 

Sulfimines 175 are obtained in excellent yield by Staudinger condensation of sulfin-amide 174 with trifluoropyruvates. In contrast, and quite surprisingly, the Staudinger reaction of terf-butylsulfinamide 182 with the pyruvates under the same conditions does not work. Sulfimines 175 are alkylated with Grignard reagents in good yields but with poor to moderate diastereoselectivities (see Scheme 9.39) [67]. 

The reaction of diisopropyl 2-(methoxycarbonyl)ethylphosphonate with Grignard reagents mediated by Ti(Oz-Pr)4 or Mc IKOZ-Pr), in THF at 0°C is completely diastereoselective and gives diisopropyl 2-(2-substimted-l-hydroxy-cyclopropyl)ethylphosphonates in good yields (60-71%). ... 

Michael addition to (+)-pu]egone [( + )-12] is not only possible with carbon nucleophiles, but also nitrogen and sulfur compounds. Thus, reaction of (+)-pulegone with benzylamine, followed by reduction of the carbonyl group with sodium borohydride, gives (1 / .3/ ,4,S )-8-(ben-zylamino)menthol (24)28, used for the formation of chiral 1.3-oxazines which react with Grignard reagents diastereoselectively (Section D. 1.3.1.4.). 

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