Aldol-Peterson reaction

Ketones are rarely used as electrophiles in the enantioselective aldolization while they find application to enantioselective olefination reactions such as the Horner-Wadsworth-Emmons or the Peterson reaction. For instance, the deprotonation of an achiral phos-phonoacetate by a set of chiral 2-aminoalkoxides led to the corresponding enolate that... 

Stereoselectivity. See Asymmetric induction Axial/equatorial-, Cis/trans-, Enantio-, Endo/exo- or Erythro/threo-Selectivity Inversion Retention definition (e.e.), 107 footnote Steric hindrance, overcoming of in acylations, 145 in aldol type reactions, 55-56 in corrin synthesis, 261-262 in Diels-Alder cyclizations, 86 in Michael type additions, 90 in oiefinations Barton olefination, 34-35 McMurry olefination, 41 Peterson olefination, 33 in syntheses of ce-hydrdoxy ketones, 52 Steric strain, due to bridges (Bredt s rule) effect on enolization, 276, 277, 296, 299 effect on f3-lactam stability, 311-315 —, due to crowding, release of in chlorophyll synthesis, 258-259 in metc-cyclophane rearrangement, 38, 338 in dodecahedrane synthesis, 336-337 in prismane synthesis, 330 in tetrahedrane synthesis, 330 —, due to small angles, release of, 79-80, 330-333, 337... 

Chapters 1 and 2 focus on enolates and other carbon nucleophiles in synthesis. Chapter 1 discusses enolate formation and alkylation. Chapter 2 broadens the discussion to other carbon nucleophiles in the context of the generalized aldol reaction, which includes the Wittig, Peterson, and Julia olefination reactions. The chapter and considers the stereochemistry of the aldol reaction in some detail, including the use of chiral auxiliaries and enantioselective catalysts. 

Magnesium, 235 Samarium(II) iodide, 270 Titanium(IV) chloride, 304 Addition reactions to carbonyl groups—Addition of functionalized CARBON NUCLEOPHILES (see also Aldol reaction and other specific condensation reactions, Meth-ylenation, Peterson Olefination, Refor-matsky reaction, Wittig reaction, Wittig-Horner reaction)... 

Synthesis and Reaction Chemistry of a,p-Unsaturated Acyl Complexes Derived from (2). Two methods for the preparation of optically active ( )- and (Z)-a,p-unsaturated iron acyls from (2) have been reported." One method involves aldol condensation of (2) with aldehydes followed by 0-methylation to produce diastereomeric acyls (18). This mixture (18) is then treated with Sodium Hydride to produce predominantly ( )-a,p-unsaturated acyl complexes (19) (eq 13). Alternatively, (2) can be depro-tonated and treated with Chlorotrimethylsilane to produce the C-silylated complex which is subsequently deprotonated and treated with an aldehyde. This Peterson alkenation produced mixtures... 

Aldol reaction and other specific condensation reaciKMu, Meth> Venation, Peterson Olcfination. Rcfoi-matsky reaction. Wtttig reacbon, Witrig Homer teaetkm)... 

Tylonolide hemiacetal (33), the aglycone of the antibiotic tylosin, possesses an anti 14-hydroxymethyl-15-acyloxy stereochemistry conveniently contained in 26, which may be viewed as the western half of 33. In order to prepare the eastern half of 33, an aldol reaction leading to the desired syn stereochemistry at C-3 and C-4 is exploited. The reaction of achiral aldehyde 27 with the S-boron enolate 28 proceeds with the expected diastereofacial selectivity to provide, in a combined yield of 80% after O-silylation, a separable mixture of 29 (derived from the / -enantiomer of 27) and 30 (from the S-enantiomer of 27). Subsequent functional group transformation of 30 ultimately leads to the a-(TMS)methylketone 31. The anion of 31, generated with lithium hexamethylsilazide in THF at — 78 °C, undergoes a Peterson condensation with 26 to afford in 60% yield the seco-diC d 32. Treatment of 32 with 70% acetic acid at 85 °C for one hour affords 33 in 60% yield. The attractive feature of this... 

Floreancig completed the total synthesis of (+)-dactylohde via a sequential Peterson olefination and an intramolecular Hosomi-Sakurai-Prins cycli-zation of the acetal-linked substrate (Scheme 32). Macrocychzation was performed by Horner-Emmons olefination as Smith did (Sect. 3.2.1). The key element of 2,6-cfs-tetrahydropyran in 155 was constructed via the sequential cyclization starting from acetal 156, which involved aldehyde 157 and 1,3-diol 158, synthesized via Denmark s asymmetric aldol reaction and Stille coupling. 

Compared to the aldol addition, the stereochemical scheme is complicated by the fact that the Michael acceptor may not always and not exclusively adopt the -configuration as shown in 421 but also as Z-diastereomer. The effect of this isomerism has been addressed in a fundamental contribution of Corey and Peterson, which is also one of the first applications of an auxiliary-based stereoselective Michael addition. The chiral lithium enolate 425 that was generated from the propionic ester 424 of phenylmenthol by deprotonation was assumed to adopt the enolate in fcr /is-configuration, in accordance with Ireland s model (cf Section 2.1). The reaction of the enolate with ( )- and (Z)-methyl crotonate led to the Michael products sy/i-426 and a f/-427, respectively. The Michael addition to ( )-crotonate was faster at low temperatures than that of the (Z)-diastereomer and provided higher chemical yields as well as syw-anti-selectivity and induced stereoselectivity. A closed, eight-membered transition state model 428 has been proposed that plausibly explains the opposite stereochemical outcome depending on the double-bond configuration of the Michael acceptor. As the rear side is shielded by the bulky 2-phenyl-2-propyl substituent, the attack of both croto-nates occurs at the Si-face of the enolate 425. Whereas Si-face of ( )-crotonate is selected for the addition of the enolate, the attack to (Z)-crotonate occurs predominantly from the e-face (Scheme 4.92) [206]. 

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