Alkynyl enol esters

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

One route to (l-alkynyl)phosphonic esters depends on the base-catalysed destruction of enol phosphates (123) obtained in situ from (2-oxoalkyl)phos-phonates in the case of (123) (R = Et), a mixture of (1-butynyl)- and (2-butynyl)-phosphonic esters was obtained, but in all other quoted cases only the acetylenic compound was obtained. A second route starts with diethyl (trichloromethyl)-phosphonate (a reagent of increasing synthetic importance) followed by sequential reaction in one-pot with BuLi (two equivalents), an aldehyde (RCHO), and a lithiumdialkylamide, and gives the products (Et0)2P(0)CsCR in very high yields. ... 

Matsuda and co-workers found that silyl enol ethers of thiol esters are good nucleophiles in the reaction with propargylic-type esters to form p-alkynyl thiol esters in the presence of a catalytic amount of [Ir(cod)(POPh3)2]OTf 32 [37]. The acetoxy group of 29 was readily substituted at 25 °C to form thiol ester 31 with 93% yield by simply stirring together 29,4 equiv of silyl enol ether 30, and 32 (5 mol%) (Eq. 16). 

Addition to linear 1,1-disubstituted allylic acetates is slower than addition to monosubstituted allylic esters. Additions to allylic trifluoroacetates or phosphates are faster than additions to allylic carbonates or acetates, and reactions of branched allylic esters are faster than additions to linear allylic esters. Aryl-, vinyl, alkynyl, and alkyl-substituted allylic esters readily undergo allylic substitution. Amines and stabilized enolates both react with these electrophiles in the presence of the catalyst generated from an iridium precursor and triphenylphosphite. 

RLi (R = 1°, 2°, 3° alkyl aryl vinylic alkynyl ester enolate)... 

RLi (R = alkyl, vinylic, alkynyl, aryl, CljCH, C13C, Br2CH), RMgX (R = alkyl), ketone and ester enolates... 

The addition of Grignard reagents or organolithiums (alkenyl, alkyl, alkynyl, allyl or aryl) to nitroenamines (281)213 was reported by Severin to afford P-substituted-a-nitroalkenes.214 b Similarly, ketone enolates (sodium or potassium), ester enolates (lithium) and lactone enolates (lithium) react to afford acr-nitroethylidene salts (294) which, on hydrolysis with either silica gel or dilute acid, afford 7-keto-a,(3-unsaturated esters or ketones (295)2l4c-d or acylidene lactones (296).214 Alternatively, the salts (294, X s CH2) can be converted to -y-ketoketones (297) with ascorbic acid and copper catalyst. 

The trans allylic alcohol needed to make this compound was made using one of the methods we introduced in Chapter 3i reduction of an alkynyl alcohol with LiAlEL]. Here is the full synthesis alkylation of an ester enolate with prenyl bromide gives a new ester, which itself is turned into an alkylating agent by reduction and tosylation. The alkyne is introduced as its lithium derivative with the alcohol protected as a THP acetal. Hydrolysis of the acetal with aqueous acid gives the hydroxy-alkyne needed for reduction to the E double bond, which is then epoxidized. 

Reaction of enyne-esters and -amides and 2-alkynyl-substituted aromatic ketones in a related fashion led to pyrranylidene complexes (Scheme 8). Compounds with a stabilized anion or a trialkylsilyl enolate in the 4- or 5-position relative to the alkyne can be used in related reactions to give carbocyclic products (Scheme 9). 

Simple a,3-unsaturated aldehydes, ketones, and esters (R = C02Me H > alkyl, aryl OR equation l)i, 60 preferentially participate in LUMOdiene-controlled Diels-Alder reactions with electron-rich, strained, and selected simple alkene and alkyne dienophiles, - although the thermal reaction conditions required are relatively harsh (150-250 C) and the reactions are characterized by the competitive dimerization and polymerization of the 1-oxa-1,3-butadiene. Typical dienophiles have included enol ethers, thioenol ethers, alkynyl ethers, ketene acetals, enamines, ynamines, ketene aminals, and selected simple alkenes representative examples are detailed in Table 2. - The most extensively studied reaction in the series is the [4 + 2] cycloaddition reaction of a,3-unsaturated ketones with enol ethers and E)esimoni,... 

There are a number of variations of the condensation reaction of acid derivatives. The reaction between a cyclic ketone having a pendant alkynyl ester unit and tetra-butylammonium fluoride leads to cyclization to a bicyclic alcohol with an exocyclic allene moiety. A chain-extension reaction culminates in acyl addition of an ester enolate. The reaction of a p-keto ester, such as methyl 3-oxobutanote and EtZnCH2k leads to chain extension via a carbenoid-like insertion reaction (p. 803), which reacts with an aldehyde in a second step to give a methyl 3-oxopentanoate derivative with a —CH(OH)R group at C-2 relative to the ester carbonyl. ... 

The six amino acids 63 were prepared individually, and mixed to give acids M-64 (see Scheme 13.15) [51]. Esterification of M-64, zinc-chelated ester enolate Claisen rearrangement of M-65, tert-butyl esterification, and removal of the Me3Si group yielded M-66. The alkynyl allenes M-67 were obtained by Af-propargylation. The allenic Pauson-Khand reaction of M-67 afforded three products (/ )-alkylidenecyclopentenone... 

Conjugate additions of enolates to alkynyl-ketones or to alkynyl-esters are further variations on the synthetic theme. 

A mixture of THF and DMPU has been used as a solvent for Sml2 in various reactions such as cyclization of alkynyl halides [90,91], tandem iodo-enone cy-clization/samarium enolate aldol reaction [92], coupling of (3-silylacrylic esters [93], deprotection of arenesulfonamides [94] and pyridine-2-sulfonamides [95], radical ring-opening reactions of cyclopropyl ketones and the trapping of the resulting samarium(III) enolates by a variety of electrophiles [96] (Scheme 41). 

Stitle coupling of 2-carboxyethyl enol inflates with organostannanes.1U In the presence of Pd(OAc)2/P(C6H )3 (1 2) or Pd[P(Q,H5)i]4, the enol triflatcs of /3-keto esters couple with vinyl-, ally -, and alkynyl(tributyl)stannancs, but not with phcnyltributyltin. 

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