Double conjugated

Scb m 7.1S. Selective cis or tions double conjugate addition of Et Zn to o/clohoradlenone monoacetal 66. 

Ethyleneimine reacts with (p-tolylsulfonyl)acetylene to give only the (Z)-product 115 via trans addition (equation 91), while primary and secondary aliphatic amines afford ( )-products76. With nonterminal acetylenes such as l-(ethylsulfonyl)-l-propyne, the reactions of ethyleneimine, n-propylamine and f-butylamine give mixtures of ( )- and (Z)-adducts. The double conjugate addition of sodium sulfide, selenide and telluride to bis(l-propynyl)sulfone (116) produces heterocycles (117) as illustrated in equation 9277. 

Scheme 7.18. Selective cis or trans double conjugate addition of Et2Zn to cyclohexadienone monoacetal 66.

Figure 3 The MALDI-TOF mass spectrum of the chymotrypsin conjugate with a ST-PHPMA-NHNH2 fraction = 1,400). The peaks 1, 2, and 3 are the double-charged, single-charged conjugate, and single-charged double conjugate aggregate, respectively.

An efficient double conjugate addition of ethane and propane dithiols in the presence of sodium methoxide to propargylic carbonyl compounds (127) has been developed. The corresponding amino-substituted propargylic aldehydes afforded piperidine derivatives.182... 

The double conjugate addition of sulfide to the dienones 540 leads to 3-aryltetrahydrothiopyran-4-ones. The dienones are obtained from the reaction of electron-rich a-bromostyrenes with ot,(3-unsaturated aldehydes. When the latter is 3-phenylpropenal, a diastereomeric mixture resulted in which the trans-isovaet was predominant (Scheme 223) <2006EJ04044>. 

In the presence of NaOMe, 5-substituted 5-hydroxypent-2-ynals, -ynones and -ynoates take part in a double conjugate addition of a dithiol which is followed by cyclisation to a tetrahydropyran. The initial product is a p-keto dithiane (a mono-protected 1,3-diketone) which spontaneously cyclises to the lactol or lactone (Scheme 6) <06JOC2715>. 

The double conjugate addition of dithiols to propargylic ketones offers a facile route to [3-keto 1,3-dithianes that can function as masked 1,3-dicarbonyl compounds and provide access to spiroketals. When the alkynic substrate contains an additional electrophilic centre, a tandem eyclisation can accompany thiane formation (Scheme 30) <03OBC15>. 

The key step in a short synthesis of ( )-tylophorine77 is an intramolecular double conjugate addition reaction. Reaction of the ( , )-unsaturatcd ester 1 (R2 = 8-phcnylmcnthyl) with ferf-butyldimethylsilyl triflate in the presence of excess of triethylamine in dichloromethane produces an 80 20 inseparable mixture of the indolizidines 2A and 2B78. Treatment of a mixture of 2A and 2B (R2 = 8-phenylmethyl) with sodium hydride in refluxing tetrahydro-furan for 2.5 hours gives the single indolizidine 2 A. Dioxanyl ester 1 furnishes, on reaction with... 

The same chemists report that 2-n-butylthiomethylenecycIohexanone (2) undergoes double conjugate addition with dimethylcopperlithium in ether at 0° to give, after hydrolysis, 2-isopropylcyclohexanone (5) in over 95% yield. 

Conjugate hydrocyanation of oc -unsaturated carboxylic esters, acid chlorides, and acyl cyanides, is effected by reaction with diethylaluminium cyanide [e.g. (128) — (129)]. The acid chloride and cyanide are the most reactive. A double conjugate addition of nitromethane with a 2-methylene-4-en-3-one (130) gave a... 

We need carbonyl groups to do conjugate addition so the tertiary alcohols will have to be made from them. In Chapter 9 (p. 222) we saw how to make such tertiary alcohols from esters and organometallic compounds and in Problem 1 of this set we saw how to do double conjugate additions on unsaturated esters - all the pieces fit together. 

Finally, a double conjugate addition of MeNH2 to the dienone forms the bicyclic amine, uiiugate addition probably occurs first on the more electrophilic chloroenone, though it doesn t -ch matter. There is some stereoselectivity in that the remaining Cl prefers the equatorial position he new six-membered ring but this is thermodynamic control as that position is easily enolized. 

The additions of several 1- and 2-carbon fragments to xenobiotics are widely recognized as conjugation reactions. These Include formylatlon, methylation, acetylation, hydroxymethylatlon, and glycolic acid formation. Since these conjugations result In less polar or only slightly more polar (but not Ionized) compounds, they will not be considered further In this review. However, some of the above occur with metabolites which exist as double conjugates. 

Conjugation usually renders xenobiotics sufficiently polar for facile excretion, but occasionally double conjugates are produced (Table I). Two of the most unusual double conjugates arise from dlchloran (Figure 1) and 4-dlmethylamlnoazobenzene (Figure 17). 

The sulfate-glutathione adduct represented 27Z of the biliary metabolites from 4-dlmethylamlnoazobenzene. Another novel double conjugate Involves viloxazine which Is converted to a sulfate-hippurate (98, 99). 

Several thiols and dithiols underwent double conjugate addition with conjugated terminal acetylenic ketones in the presence of [bmim][OH], to produce the corresponding p-keto 1,3-dithane derivatives (Fig. 12.23). It should be noted that in the case of C-S Michel addition, [bmim][OH] was diluted with another neutral ionic liquid, [bmim][Br], to get the best results. These compounds are of much importance in organic synthesis. 

Recently Gallice et al. used high-performance liquid chromatography (HPLC) and nuclear magnetic resonance spectroscopy (NMR) to identify a double conjugate of glucuronidate-o-hydroxyhippuric acid in ultrafiltrates of uremic plasma (G6). This compound had been previously described by Zimmerman et al. as a fraction of the so-called uremic middle molecules (Z7, Z8). So far no data have been reported on the toxicity of this compound. 

Z8. Zimmerman, L., Jomvall, H Bergstrom, J., et al., Characterization of a double conjugate in uremic body fluids. Glucuronidated o-hydroxybenzoylglycine. FEBS Lett. 129, 237-240 (1981). 

Stereochemical control in the double conjugate addition Tandem Reactions as Polymerisation Terminated by Cyclisation The MIMIRC sequence with vinylphosphonium salts Tuning the MIMIRC sequence with different Michael acceptors Heterocycles by Tandem Conjugate Additions Tandem conjugate addition and Mannich reaction Tandem Conjugate Addition and Aldol Reaction... 

Double conjugate addition of A,A -dimethyl-l,2-diaminoethane with 2,3-bis(benzenesulfonyl)-1,3-butadiene, followed by a facile thermal elimination of PhS02H, affords hexahydrodiazocine (7), together with the piperazine resulting from alternative nucleophilic displacement of PhSOf from... 

Double conjugate addition of A-ethyl-2-aminoethanol to 2,3-(>iXphenylsulfonyl)-1,3-butadiene... 

A new method for spiroannelation involves the double conjugate addition of the bis-cuprate reagents (33) to /8-halocycloalkenones (Scheme 11) ... 

This is a simple case of a double conjugate addition of ammonia to a dienone. 

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