Amides y-unsaturated

Asymmetric dihydroxy lation of substituted aryl allyl ethers also proceeds with high enantioselectivities (89-95% ee) providing that there are no ortho substituents on the aryl group. Dienes, polyenes, and enynes can also be regioselectively dihydrox-ylated (eq 2-5). In some cases, such as in the asymmetric dihy-droxylation of a,3- and 3,y-unsaturated amides, the amount of... 

Yamamoto and co-workers have reported the decarboxylation-carbonylation reaction of aUyl carbamates to afford /3,y-unsaturated amides (Scheme 57),... 

The allylic nitrogen derivatives, such as allylic ammonium salts, tosylimides, and nitro compounds, react with Pd(0) species under mild reaction conditions to form rr-allylpalla-dium intermediates, which undergo coupling reaction with various nucleophiles to give allylated nucleophiles. Carbon monoxide reacts with the 7r-allylpalladium species derived from allylamines to give /3,y-unsaturated amides. 

Y-Unsaturated amides can be prepared from allylamino [1], allylphosphate [2], or allylalcohol [3] with a one-carbon atom increase. Some of these are not stereodefined, and others require the use of valuable noble metal catalysts and carbon monoxide. However, it is possible to synthesize in a stereodefined manner ( )-p,-y-unsaturated amides from -9-alkenyl-9-BBN with N,N-dialkyl(di-methylsulfuranylidene)acetamide [4] with a two-carbon increase. N,N,-Di-alkyl-a-sulfonium substituted amides are easily prepared by the reaction of dimethylsulfide and N,N-dialkyl-a-bromoacetamide [5]. The terminal -9-al-kenyl-9-BBN generated [6] in situ reacts (Scheme 11.1) with N,N-dialkyl(dimet hylsulfuranylidene)acetamide, prepared from JV,JV-dialkyl-a-sulfonium-substi-tuted amide and sodium hydroxide at 0 °C in THE The reaction mixture after oxidation with HjOj/OAc affords ( )-p,y-unsaturated amides in 60-70% yields (Table 11.1) [4], The mechanism of the reaction is depicted in Scheme 11.2. 

A vivid illustration of this phenomenon is in the reduction of the /3,y-unsaturated amide 1 with tritium gas in the presence of 10% Pd/C to provide 2, a tritium-labeled phospholipase A2 inhibitor. Product 2 had a specific activity of 85 Ci/mmol, in contrast to the theoretical maximum of 58 Ci/mmol from direct addition of two tritium atoms to the double bond. 

Loh, T.P., Cao, G.Q., and Yin, Z. (1999) A new method for the synthesis of 3,Y-unsaturated amides from allylic carbonate catalyzed by palladium in the presence of carbon monoxide and amine Studies towards the total synthesis of antillatoxin. Tetrahedron Lett., 40, 2649-2652. 

This procedure illustrates a general method for preparing aliphatic and, in certain cases, aromatic /3-lactarns containing a free NH group and substituted in either the 4 position or in both the-3 and 4 positions of the 2-azetidinone ring. The major byproduct of the cycloaddition step is a /3,7-unsaturated carbox-amide-N-sulfonyl chloride which, in the case of certain aromatic olefins, may predominate. Reactions of both /3-lactam-N-sulfonyl chlorides and the /3,y-unsaturated carboxamide-N-sulfonyl chlorides have been tabulated.3... 

A reaction which transforms allylic alcohols to homologous P.y-unsaturated amides by means of a 2,3-sigmatropic process was first described by BUchi. When an allyl alcohol is heated with A -di-methylformamide aceuil, a rearrangement occurs apparently involving a nucleophilic carbene as an intermediate, leading to a product with 95-100% ( )-geometry of the double bond (Scheme 47). 

Reaction with amides. Benzamides and thiobenzamides are converted to a,a-disubstituted benzylamines. Tertiary amides form ketones on reaction with RCeCl even when the reagent is present in large excess, therefore Weinreb amides are not necessary for the ketone synthesis. Enaminones are also attacked at the carbonyl group, and in the cases of a -silylated derivatives the reaction products are 3,y-unsaturated ketones. ... 

Reaction with olefins,2 The reagent reacts with an olefin to give a /3-lactarn-N-sulfonyl chloride and a /3,y-unsaturated N-chlorosulfonylamide the former product usually predominates except in the case of certain aromatic olefins. Thus isobutylene reacts to give the lactam (1) in 70% yield and the amide (2) in 30% yield. Under the conditions of workup the minor product (2) is readily hydrolyzed... 

Synthesis of Alkenes by Reductive Elimination. The treatment of 2-halo-3-hydroxy esters and amides with samarium iodide leads to the corresponding di- or trisubstituted E)-a,p-unsaturated derivatives in high yields and diastereoselectivities (eqs 39 and 40). The precursors are readily accessible by condensation of the lithium enolate of a-haloesters or amides. If the substrate contains y,i5-unsaturation, the /3,y-unsaturated ester is generated in the process (eq 41). 

Opening of a, -Epoxy Esters and Amides. Treatment of aromatic a,/3-epoxyamides with samarium iodide leads to the highly stereoselective synthesis of a./S-unsaturated amides with high diastereocontrol (eq 52). If the reaction is run on a substrate that contains y-protons, then a base-promoted reaction produces the (E)-a-hydroxy-, y-unsaturated amide (eq 53). ... 

The efQciency of these catalytic reactions of epoxides is ascribed to the eminent nucleophilic character of the Pd(0) catalyst and hydrogen-carrying ability of Pd(II) species. " In principle, the diene epoxide is susceptible to Pd(0) attack at C-2 (SN2-type reaction), C-4 (SN2 -type reaction), or C-3-C-4 double bond. /3,y-Unsaturated ketone would form via zwitterion and Pd hydride intermediate, while, alternatively, the epoxide can isomer-ize to dienols through the 7r-allyl complex (Scheme 7). The Tt-allyl complex is facilely scavenged with hydride, alkoxides, amides, and carboanion nucleophiles to enhance the synthetic utility (see Sect. V.2.1.5). 

The Claisen rearrangement has been used to prepare j8,y-unsaturated amides, largely as the E-isomers, from 3-(trimethylsilyl)allyl alcohols and amide acetals (Scheme 48). Overall yields and stereoselectivities are excellent. Conditions have been found under which the stereochemical outcome of the related ynamine-Claisen rearrangement can be controlled. Thus, the kinetically favoured intermediate is the E-enamine (140) which leads to the "trans product (142), whereas the Z-isomer (141) is thermodynamically favoured and gives the cw ... 

The Sasai research group found an intramolecular Heck-type approach to simple 3-pyrrolin-2-ones (Scheme 50 2010CC9064). For example, treatment of P,y-unsaturated amide 218 with palladium acetate in the presence of the isoxazoline ligand 219 and p-benzoquinone gives 3-pyrroUn-2-one 220 via a S-endo-trig cyclization. 

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. 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

When the enolate of an ,) - or a /j,y-unsatunited amide is used, it can react in an a or in a y fashion with a,/i-unsaturated esters, however, in most cases only a-selectivity is observed. Using l-(l-oxo-2-butenyl)pyrrolidine and lithium diisopropylamide at — 78 °C in a THF/HM-I A mixture (1 1), high. syn-selective formation of 3-alkyl-5-oxo-5-(l-pyrrolidinyl)-4-vinylpen-tanoates is achieved78,381 382. Related syn- or anti-selective additions of a vinylogous urethane also are known79. 

---