Cyclic a,P-unsaturated

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

Cyclic a,p-unsaturated ketones can be cleaved by treatment with base of their epoxy tosylhydrazone derivatives to give acetylenic ketones. The reaction can be applied to the formation of acetylenic aldehydes (R=H) by using the corresponding, 2,4-dinitrotosylhydrazone derivatives.Hydrazones (e.g., 47) prepared from... 

The use of cyclic a,p-unsaturated ketones as starting materials in the enantioselective addition of dimethyl- and diethylzinc reagents catalysed by the HOCSAC ligand was introduced by Walsh and Jeon, in 2003. As shown in Scheme 4.16, the corresponding cyclic tertiary alcohols were formed in high enantioselectivities of up to 99% ee. 

Scheme 4.16 Additions of ZnR2 to cyclic a,P-unsaturated ketones with HOCSAC ligand.

A variety of imidazolidinium and pyrrolidinium salts (Fig. 2.38) have been found to catalyze the reaction between nitrones and cyclic a, p-unsaturated aldehydes, affording bicyclic adducts with high diastereoselectivity and enantioselec-tivity (Scheme 2.256) (759). 

A cyclic a,p-unsaturated amide can also be employed in the rhodium-catalyzed... 

Hanessian described the facile addition of cyclic and acyclic nitroalkanes to cyclic a,P-unsaturated ketones using L-proline 58 as the catalyst (3-7 mol%) in the presence of 2,5-dimethylpiperazine [100], The reactions proceeded efficiently at room temperature and consistently provided adduct 59 with increased levels of enantioselectivity when compared with the rubidium prolinate method disclosed by Yamaguchi [29] (Scheme 24). The presence of trace amounts of water in the reaction was found to be essential, suggesting a hydrolytic step is involved in the catalytic... 

Chen extended the scope of his iminium ion catalysed [3+2] cycloaddition with azomethine imines (see Sect. 2.1.2) to encompass cyclic a,P-unsaturated ketone substrates using primary amine 147 as the catalyst [194]. Interestingly, the presence... 

List later applied this strategy to the 1,4 reduction of various acyclic and cyclic a,P-unsaturated ketones using the diasteriomeric salt 15 (Scheme 5.37) [66]. Notably, use of the opposite (S) phosphate counterion resulted in a matched/ mismatched ion pair combination, forming the same enantiomer of the product but in significantly diminished ee. 

Isophorone. Isophorone (3,5,5-trimethyl-2-cyclohexen-l-one) is a cyclic a,p-unsaturated ketone derived from the trimerization of acetone. It has a light yellow color and a disagreeable camphoraceous odor. It has the tendency to discolor and form residues on prolonged storage. Isophorone is completely miscible with organic solvents, and other physical properties are listed in Table 1. 

As an extension of this highly enantioselective Michael addition of silyl nitronates with a, p-unsaturated aldehydes, the reactions with cyclic a,p-unsaturated ketones as a Michael acceptor were also tested (Scheme 9.15). Cyclohexenone and cyclohepte-none were employed as a useful Michael acceptor with various silyl nitronates in the presence of catalyst (R,R)-6c, and gave the corresponding enol silyl ethers 28 with excellent stereoselectivities [30]. 

In the total synthesis of (—)-secodaphniphylline, an asymmetric [l,4]-conjugate addition was used to establish relative and absolute stereocontrol.The lithium enolate of a trans-2,5-dimethylpyrrolidine-derived amide adds in a Michael fashion to a cyclic a,p-unsaturated ester, with subsequent enolate trapping, to afford the desired product in 64% yield and 92 8 diastereose-lection (eq 6). 

A chiral complex of (1), L1A1H4, and A/-ethylaniline (molar ratio, 1 1 2) reduces aryl alkyl ketones to optically active alcohols in high ee. a, -Unsaturated ketones are reduced enantioselectively to afford optically active (S)-allylic alcohols with 80-98% ee. An intermediate in an anthracyclinone synthesis is prepared in 92% ee by the enantioselective reduction of a cyclic a,p-unsaturated ketone (eq 2). ... 

Cyclic a,p-unsaturated ketones can be cleaved by treatment with base of... 

The naturally occurring ionone pair 37 and 38 demonstrate again that the effect of conjugation on acyclic carbonyl NMR chemical shift is smaller than that for cyclic a,P-unsaturated ketones. 

The total synthesis of galbulimima alkaloid GB 13 was accomplished by L.N. Mander and co-workers. The Birch reduction of a complex intermediate was necessary in order to prepare a cyclic a,p-unsaturated ketone. The treatment of the substrate with lithium metal in liquid ammonia first resulted in a quantitative reductive decyanation of the C6a cyano group. The addition of excess ethanol to the reaction mixture reduced the aromatic ring to the corresponding enol ether that was hydrolyzed in a subsequent step to afford the unsaturated ketone. 

Cyclic a,p-unsaturated N, V-dimethylhydrazones may be monoalkylated cleanly at the a- or a -posi-tion depending upon the conditions of formation of the metallated unsaturated hydrazone. By using (i) less reactive bases such as sodium hydride (ii) additives such as HMPA and/or (iii) allowing the metallated hydrazone to stand for a period of time before the alkylating agent is added, a-alkylations via the... 

Carbonylation of the cuprate reagent, R (CN)CuLi2, prepared from copper(I) cyanide and an alkyl-lithium, gives a product which can be used for the direct nucleophilic 1,4-acylation of a,3-unsaturated aldehydes and ketones (equation 16). The reaction works particularly well with cyclic a,p-unsaturated ketones to give high yields of the expected 1,4-diketone. 

The Corey-Bakshi-Shibata reduction (CBS reduction) is a highly enantioselective method for arylketones, diaryl ketones, and dialkylketones. In addition, cyclic a,p-unsaturated ketones, acyclic a,p-unsaturated ketones, and a,p-ynones are reduced enantioselectively in a 1,2-fashion. The high enantioselective nature of this reduction relies on the chiral oxazaborolidine catalyst, shown in the reaction scheme, in the presence of borane or a dialkylborane. Reviews (a) Singh, V. K. Synthesis 1992, 605-617. (b) Deloux, L. Srebnik M. Chem. Rev. 1993,93,163-1. (c) Corey, E. J. Helal, C. J. Angew. Chem. Int. Ed. 1998, 37. 1986-2012. 

The addition of diethyl 1-bromo-l,1-difluoromethylphosphonate to various electron-deficient alkenes initiated by a cobaloxime(III)/Zn bimetallic system gives the corresponding diethyl difluoro-alkylphosphonates (1 1 Michael-type adducts) in moderate to good yields (34-72%). Cyclic a,p-unsaturated ketones and electron-rich alkenes produce somewhat lower yields of addition products (18-58%), along with small quantities of diethyl difluoromethylphosphonate. A radical mechanism has been proposed for this process. ... 

It has been shown recently that 3-oxocycloaIkylphosphonates can be prepared by photochemical phosphonosilylation of cyclic a,P-unsaturated ketones. Thus, irradiation of a mixture of dialkyl trimetylsilyl phosphite and cyclic a,P-unsaturated ketones in MeCN provides essentially conjugate... 

There have been frequent reports of the condensation of cyclic a,p-unsaturated ketones at the 7-position an example is seen in equation (88).102 Other 3-methyIcyclohexenones have been reported to undergo similar reactions.103 Unfortunately, the original literature does not report yields for these transformations. These reactions would bear reinvestigation with modem methods of analysis. Other cy-clohexenones have also been found to undergo aldol condensation at the 7-position. For example, car-vone condenses with two equivalents of benzaldehyde (equation 89).104... 

The Michael addition of amines to a,p-unsaturated thioamides has been carried out [43]. The reaction of tertiary a,p-unsaturated thioamides 59 with cyclic amines such as pyrrolidine, morpholine, and piperidine proceeds slowly (Eq. 19). After five days, the adducts 60 are obtained as stable compounds in moderate yields. On the other hand, the products derived from the addition of pyrrolidine to secondary a,p-unsaturated thioamides 61 are unstable. The stereochemistry of the Michael addition to cyclic a,p-unsaturated thioamides 62 is dependent on the substituents on the nitrogen atom. 

Reduction of cyclic a,p-unsaturated ketones in which there are substituents on the (3- and y -carbon atoms could give rise to two stereoisomeric products. In many cases one isomer is formed predominantly, generally the more stable of the two. The guiding principle appears to be that protonation of the intermediate anion takes place orthogonal to the enol double bond (axially in six-membered rings). Thus,... 

In addition to allylic organolithiums reacting with conventional electrophiles such as akyl halides and carbonyl compounds, activated olefins have also been employed to provide Michael addition products [86,87,105]. Both mono- and diactivated olefins including a,p-unsaturated ketones, esters, malonates, malo-nitriles and nitro compoimds are compatible (Scheme 49). Addition of the orga-nolithium to cyclic a,p-unsaturated carbonyl compoimds occurred with retention of configuration, whereas addition to other activated olefins proceeds with inversion. 

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