Allylic alcohol amides from

O-Allyl imidate esters undergo [3,3]-sigmatropic rearrangements to /V-allyl amides. Trichloromethyl imidates can be made easily from allylic alcohols by reaction with trichloroacetonitrile. The rearrangement then provides trichloroacetamides of IV-allylamines.260... 

Kang and co-workers prepared the (3-halo amide arrangement required for oxazoline formation from allylic alcohols via a two-step process. For example, treatment of the allylic alcohol 122 with trichloroacetonitrile and base followed by activation of the double bond with iodine monochloride, provides 123. Hydrolysis of 123 gave 124 from which cyclization provided the oxazoline 18a used for paclitaxel synthesis (Scheme 8.36). 

The first step in this reaction is formation of the allyl trichloroacetimide 8 formed from allyl alcohol 3 by reaction with trichloroacetonitrile. The allyl amides 9 are formed by the [3,3]-sigmatropic rearrangement of 8, followed by hydrolysis. The reaction proceeds with good yield for primary and secondary amides however, for products where the amide nitrogen is bound to a tertiary carbon atom the yields are generally low. 

In the rearrangement of amide acetals prepared from allylic alcohols and reagent 2 the stereo-genic center is too far away from the newly created stereogenie center to exhibit any 1,5-asym-metric induction. For example, the reaction of allylic alcohol 1 with the amide acelal 2 gives diastereomers 3/4 and 5/6 as a 1 1 mixture. The structures 3 and 4 or 5 and 6, respectively, belong to amide rotamer structures646. 

Corey has reported the diastereocontrolled formation of the tetrahydropyran core of thromboxane B2 utilizing the Eschenmoser-Claisen rearrangement from allylic alcohol 305 to produce amide 307. ° lodolactonization followed tin hydride reduction afforded the lactone 308 which was subsequently transformed to the target molecule. 

Acetamides have been prepared in moderate to good yield from alcohols by reaction with acetonitrile and sulphuryl chloride. It has been found that the hydrolysis of nitriles to amides can be effected in excellent yield using potassium hydroxide in t-butanol if the amide produced is relatively insoluble in water. Experimental details for the large scale anodic oxidation of iV-formyl derivatives of amines to a-methoxyalkylamides have been recorded, and an interesting synthesis of trichloroacetamides from allylic alcohols via a thermal [Att + 2a] rearrangement has been described (Scheme 50). ... 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

Co-adsorption experiments show a complex role of the nature and concentration of chemisorbed ammonia species. Ammonia is not only one of the reactants for the synthesis of acrylonitrile, but also reaction with Br()>nsted sites inhibits their reactivity. In particular, IR experiments show that two pathways of reaction are possible from chemisorbed propylene (i) to acetone via isopropoxylate intermediate or (ii) to acrolein via allyl alcoholate intermediate. The first reaction occurs preferentially at lower temperatures and in the presence of hydroxyl groups. When their reactivity is blocked by the faster reaction with ammonia, the second pathway of reaction becomes preferential. The first pathway of reaction is responsible for a degradative pathway, because acetone further transform to an acetate species with carbon chain breakage. Ammonia as NH4 reacts faster with acrylate species (formed by transformation of the acrolein intermediate) to give an acrylamide intermediate. At higher temperatures the amide may be transformed to acrylonitrile, but when Brreform ammonia and free, weakly bonded, acrylic acid. The latter easily decarboxylate forming carbon oxides. 

Kinetic resolution can also be accomplished via eliminative pathways. Thus, the enantiomerically enriched allylic alcohol 102 can be prepared from the meso epoxide 96 with up to 96% ee by the action of LDA in the presence of the chiral diamine 101 and 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU). The DBU is believed to function as an aggregation modifier, and the active catalyst is theorized to be a heterodimer of the lithium amide (deprotonated 101) and DBU, although some nonlinear effects have been observed at low DBU concentrations <00JA6610>. Dipyrrolidino derivatives (e.g., 104) have also demonstrated utility with regard to kinetic resolution <00H1029>. 

In another report of Singh and Han [61], Ir-catalyzed decarboxylative amidations of benzyl allyl imidodicarboxylates derived from enantiomerically enriched branched allylic alcohols are described. This reaction proceeded with complete stereospecificity-that is, with complete conservation of enantiomeric purity and retention of configuration. This result underlines once again (cf. Section 9.2.2) that the isomerization of intermediary (allyl) Ir complexes is a slow process in comparison with nucleophilic substitution. 

When optically active allylic alcohol 6a and propargylic alcohol 6p were reacted with amides 2c and 2f, only racemic products 7ac, 7af, and 7pf were obtained (Scheme 2). The results suggested a mechanism through the formation of a carbe-nium intermediate. The observed racemization can also be ascribed to the reversibility of the present reaction. The result shown in Scheme 3 indicated that the reaction is reversible under the reaction conditions. When 7af was treated with 5 mol% of Bi(OTf)3 and KPF6 and 1 equiv of carbamate 2c, a mixture of 7af (28%) and 7ac (68%) was recovered after 1 h. The result suggested that Bi(OTf)3/KPF6 cleaved the C-N bond in 7af derived from sulfonamide 2f, and that 7ac is thermodynamically more stable than 7af. We assume that the desiccant (Drierite) had a beneficial effect on the reactions of substrates shown in Tables 10-12 because of the observed reversibility of the present reaction. In this reaction, the possibility... 

Allyl alcohols readily react with trichloroacetonitrile to give the corresponding trichloroacetimidates 145. Activation of the double bond with electrophilic reagents results in ring closure to yield oxazolines 146. The most commonly employed electrophiles include iodine, iodine monochloride, phenylselenyl chloride, and mercuric trifluoroacetate. Other nitriles including cyanogen bromide and N,N-dimethylcyanamide can also be used. Since oxazolines readily hydrolyze to amides, the net effect of this reaction sequence is to produce p-amino alcohols 147 from an allyl alcohol. This strategy has been employed in numerous total syntheses of natural products. Examples are listed in Table 8.18 (Fig. 8.7 Scheme 8.43). ° ... 

Decarboxylation of 117 was effected by treatment of 117 with LiCl in hot, aqueous HMPA at 105 °C providing 118 as a mixture of diastereomers that were separated and carried forward individually. Protection of the secondary amide group as the corresponding methyl lactim ether was accomplished by treating 118 with trimethyloxonium tetrafluoroborate in dichloromethane that contained cesium carbonate. Next, the indole nitrogen atom was protected as the corresponding Boc derivative by treatment with dicarbonic acid bis(rm-butyl)ester in the presence of DMAP and the silyl ether was removed with tetrabutylammonium fluoride to provide diol 119 in 52-78% overall yield from 118. Selective conversion of the allylic alcohol to the corresponding... 

Quite recently, new methods for stereocontrol in cyclizations of /V-acylami nomethyl ethers have been developed. N,0-acetals of type (19 Scheme 13) were prepared from the corresponding secondary allyl alcohol and the diastereomers were separated by chromatography and/or crystallization. Cyclization with mercury(II) salts and reduction of the organomercury intermediate proceeded with high stereocontrol exerted by the amidal stereogenic center, not the stereogenic center on the original alcohol.237 ... 

Preparatively more relevant is the use of chiral lithium amide bases, which have been successfully used both for enantioselective generation of allylic alcohols from meso-epoxides and for the related kinetic resolution of racemic epoxides [49, 50]. In many instances, chiral amide bases such as 58, 59, or 60 were used in stoichiometric or over-stoichiometric quantities, affording synthetically important allylic alcohols in good yields and enantiomeric excesses (Scheme 13.28) [49-54], Because of the scope of this review, approaches involving stoichiometric use of chiral bases will not be discussed in detail. 

The N,N-dimclhylkclcniminium cation (46) is not formed directly from DMAc, but via its enol form (52), see Scheme 19. The formation of the enol form (imine form) is strongly facilitated by the presence of lithium ions, which coordinate to the amide oxygen. Also the intermediacy of enol precursor 52 was proven by means of trapping reactions in the presence of allyl alcohol as the trap, the enol 52 formed an allyl enol ether, which at the prevailing elevated temperatures immediately underwent a Claisen-type rearrangement to produce 4-pentenoic acid N,N-dimethylamidc (53) (Scheme 20). This... 

---