Allyl propionate, addition

The excess of N-chlorosuccinimide is destroyed by the addition of about 15 drops of allyl alcohol and 180 ml of water is then added with stirring. This mixture is held at 0°C for about one hour. The precipitated 16/3-methyl-1,4-pregnadiene-9o-chloro-11/3,17o,21-triol-3,20-dione-21-acetate is recovered by filtration. A solution of 250 mg of the chlorohydrin in 5 ml of 0.25N perchloric acid in methanol is stirred for about 18 hours at room temperature to produce 16/3-methyl-9o-chloro-11/3,17o,21-trihydroxy-1,4-pregnadiene-3,20-dione which is recovered by adding water to the reaction mixture and allowing the product to crystallize. Propionic anhydride is then used to convert this material to the dipropionate. 

Johnson s classic synthesis of progesterone (1) commences with the reaction of 2-methacrolein (22) with the Grignard reagent derived from l-bromo-3-pentyne to give ally lie alcohol 20 (see Scheme 3a). It is inconsequential that 20 is produced in racemic form because treatment of 20 with triethyl orthoacetate and a catalytic amount of propionic acid at 138 °C furnishes 18 in an overall yield of 55 % through a process that sacrifices the stereogenic center created in the carbonyl addition reaction. In the presence of propionic acid, allylic alcohol 20 and triethyl orthoacetate combine to give... 

Intermolecular hydroalkoxylation of 1,1- and 1,3-di-substituted, tri-substituted and tetra-substituted allenes with a range of primary and secondary alcohols, methanol, phenol and propionic acid was catalysed by the system [AuCl(IPr)]/ AgOTf (1 1, 5 mol% each component) at room temperature in toluene, giving excellent conversions to the allylic ethers. Hydroalkoxylation of monosubstituted or trisubstituted allenes led to the selective addition of the alcohol to the less hindered allene terminus and the formation of allylic ethers. A plausible mechanism involves the reaction of the in situ formed cationic (IPr)Au" with the substituted allene to form the tt-allenyl complex 105, which after nucleophilic attack of the alcohol gives the o-alkenyl complex 106, which, in turn, is converted to the product by protonolysis and concomitant regeneration of the cationic active species (IPr)-Au" (Scheme 2.18) [86]. 

Feringa reported an enantioselective allylic oxidation of cyclohexene to optically active 2-cyclohexenyl propionate 25 by using a chiral copper complex prepared from Cu(OAc)2 and (S)-proline, as chiral catalyst (Scheme 9.14) [32], In the absence of additives, a negative NLE was observed, whereas in the presence of a catalytic amount of anthraquinone, a positive NLE (asymmetric amplification) was observed. Moreover, higher enantioselectiv-ity was attained when enantiopure (S)-proline was used. However, the role of the additive remains elusive. 

To allow for a diverse multi-step synthesis, we transformed the 3-hydroxy-2-methyl-idene propionic acids (Fig. 6.9) into polymer-bound allylic amines, which can be considered as unusual (3-amino acid derivatives. The polymer-bound allylic alcohols were first treated with acetyl chloride and DIEA in CH2C12 to form the ester, which was reacted with primary amines in an addition elimination step to form allylic amines. 

Kinetic control. The Zimmerman-Traxler model, as applied to propionate and ethyl ketone aldol additions, is shown in Scheme 5.7 (note the similarity to the boron-mediated allyl additions in Scheme 5.3). Based on this model, we would expect a significant dependence of stereoselectivity on the enolate geometry, which is in turn dependent on the nature of X and the deprotonating agent (see section... 

Ester enolates. Oppolzer showed in 1983 that the Z(Gj-dienolate shown in Scheme 5.30a adds to cyclopentenone with 63% diastereoselectivity [160]. Additionally, the enolate adduct can be allylated selectively, thereby affording (after purification) a single stereoisomer having three contiguous stereocenters in 48% yield. The transition structure illustrated is not analogous to any of those illustrated in Scheme 5.29 because cyclopentenone is an s-trans-Z-enone, whereas the enones in Scheme 5.29 are s-cis-E. In 1985, Corey reported the asymmetric Michael addition of the EfOj-enolate of phenylmenthone propionate to -methyl crotonate as shown in Scheme 5.30b [161]. The product mixture was 90% syn, and the syn adducts were produced in a 95 5 ratio, for an overall selectivity of 86% for the illustrated isomer. The transition structure proposed by the authors to account for the observed selectivity is similar to that shown in Scheme 5.29c, but with the enone illustrated in an s-trans conformation. Intramolecular variations of these reactions were reported by Stork in 1986, as illustrated in Scheme 5.30c and 5.29d [162]. Two features of... 

Polymer bound acrylic ester is reacted in a Baylis-Hillman reaction with aldehydes to form 3-hydroxy-2-methylidenepropionic acids or with aldehydes and sulfonamides in a three-component reaction to form 2-methylidene-3-[(arylsulfonyl)amino]propionic acids. In order to show the possibility of Michael additions, the synthesis of pyrazolones was chosen. The Michael addition was carried out with ethyl acetoacetate and BEMP as base to form the resin bound p-keto ester. This was then transformed into the hydrazone with phenylhydrazine hydrochloride in the presence of TMOF and DIPEA [28]. The polymer bound phenol was readily coupled to a variety of allyl halides by using the Pl- Bu to generate a reactive phenoxide [29]. 

The solvent-free biocatalytic processes are considered more environmentally friendly, because this technology has the additional advantage of using the volume of the reactor more efficiently. For example, this system has been applied for the produaion of biodiesel, allyl and chlorohydrin acrylates, isobutyl propionate, etc. 

The allylation and crotylation of aldehydes provide attractive alternatives to asymmetric acetate and propionate aldol addition reactions for the construction of /1-hydroxy aldehydes or ketones (Scheme 5.2 see also Chapter 4). In analogy to propionate aldol addition reactions, an important stereochemical feature involving the addition of substituted allylation reagents to aldehydes is simple diastereoselectivity namely, the formation of 1,2-syn versus 1,2-anti products. Although the underlying reasons for absolute and relative induction have yet to be studied in mechanistic detail for many of these processes, there are a collection of methods that reliably and predictably furnish optically active adducts. 

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