Dienes aldehyde enamines

Electron withdrawing substituents such as aldehyde or imonium functions at the other end of the alkene or the 1,3-diene transform enamines and 1,3-dienamines into push-pull systems characteristic of dyes. Electron release (push) of the donor group shields the / , S, e,... carbons and electron withdrawal (pull) of the acceptor group (carbonyl oxygen or imonium nitrogen) deshields in the a, y,... position [343],... 

In the mid 1960s, Issidorides and Haddadin addressed some of the limitations in substitution met in earlier reported procedures by developing a synthesis of heteroaromatic A/ oxides that, upon reduction, afford heteroaromatic compounds like phenazine. The Beirut reaction, named after its origin from the capital of Lebanon, involves condensation of benzofurazan oxide (benzo[1,2,5]oxadiazole-1-oxide) and, e.g., enamines, dienes, aldehydes, a,/ -unsaturated ketones, or enolates to form heterocycles... 

The dienamines derived from enals undergo hydroboration with 9-BBN, with high regio- and chemoselectivity at the enamine carbon-carbon double bond and place the boron atom on a carbon having higher electron density. The high selectivity is confirmed by the hydroboration of a 1 1 mixture of 1-hexene and 1-morpholino-l-octene with 1 equiv of 9-BBN. The reaction mixture affords, after the addition of methanol, a 1 1 mixture of 1-hexene and 1-octene, and no 1-hexanol is detected. Consequently, this process is used to convert unsaturated aldehydes to dienes. Thus, enamine of citronellal on hydroboration-elimination affords a chiral non-conjugated diene, p-citronellene (Scheme 24.5) [1]. 

Iron carbonyls have been used in stoichiometric and catalytic amounts for a variety of transformations in organic synthesis. For example, the isomerization of 1,4-dienes to 1,3-dienes by formation of tricarbonyl(ri4-l,3-diene)iron complexes and subsequent oxidative demetallation has been applied to the synthesis of 12-prostaglandin PGC2 [10], The photochemically induced double bond isomerization of allyl alcohols to aldehydes [11] and allylamines to enamines [12,13] can be carried out with catalytic amounts of iron carbonyls (see Section 1.4.3). 

This isomerization is enantioselective when optically active BINAP is used and provides practical access to optically active aldehydes and alcohols such as L-menthol, which is a key fragrance chemical [297—299], The proposed mechanism involves amine, iminium, and enamine as complex intermediates [300], Extension of this olefin isomerization is realized in the isomerization of an alkyne to a conjugated diene (Scheme 1-47) [301], High chemoselectivity is achieved when Pd(OAc)2 or [Pd2(dba)3]/HOAc, in the presence of phosphine, is used as catalyst (Table 1-14). The phosphine of choice is dppb although dppf could give a similar yield. 

Aza-l,3-diene can be synthesized by treatment of an aldehyde with N,N-bis (trimethylsilyl)enamine in the presence of CsF. The reaction eliminates siloxane without forming water. This is an extremely useful means of producing such acid-sensitive compounds (Scheme 2.16) [31]. 

Enamines of unsaturated aldehydes can be converted into the corresponding dienes for example, citronellal, a chiral aldehyde, gives the chiral non-conjugated diene, /f-citronellene, in 92% enantiomeric excess - (Scheme 172). The combination of the Lewis hydroboration procedure with the thallium acetate acetoxylation of enamines provides a means of converting enamines into acetoxycycloalkenes (Scheme 173). The hydroboration oxidation of enamines to give -aminoalcohols was first reported by Borowitz and Williams . Cw-l,2-addition of BH3 occurs, to give the trans-ji-ammocy-... 

The stereoselectivity of the reaction was elucidated for the enaminone 354 by NMR and X-ray studies. Base treatment generates predominantly the enolate 355, which possesses a twisted diene structure, and the enamine has an E-configuration. Addition of aldehydes to the enolate 355 follows the Cram rule in an antiselective manner to give mainly the adducts 356 having threo configurations, Scheme 100 (86JOC3068 88JA7901). 

Enamine-aldehydes (80) can also serve as the diene equivalent in the hetero-Diels-Alder reaction with vinyl ethers and yields of... 

The use of enamine catalysis in the enantioselective a-functionalization of carbonyl compounds has been reviewed, including aldol, Mannich, and alkylation processes," and a short review has examined enantioselective a-alkylation of aldehydes Benzodithiolylium tetrafluoroborate (133) is a water-stable salt and can be added enantioselectively to aldehydes at the a-position in the presence of simple chiral organocatalysts, giving the corresponding alcohol. The sulfurs can be readily cleaved with H2/Raney Ni, rendering the process a formal tf-methylation of aldehydes." a ,/3-Unsaturated aldehydes undergo enantioselective a- and y-alkylation via dien-amine activation, using a diarylprolinol TMS ether as catalyst." ... 

The metal present can also catalyse other reactions, giving rise to tandem processes. If hydroformylation is carried out in the presence of a secondary amine, the aldehyde 4.136 produced by hydroformylation will condense to give an enamine 4.137, which will be hydrogenated (but not hydroformylated) under the reaction conditions to give a tertiary amine 4.138 (Scheme 4.52). This chemistry can be extended to dienes to give iV-heterocycles of various kinds (Schemes 4.53 and 4.54). ... 

In addition to the studies mentioned above, chiral alcohols have been used as H-bonding catalysts in a vinylogous aldol reaction of Chan s diene with aldehydes [73], in an enantioselective Strecker reaction [74], and in the enantioselective addition of aza-enamines to imines [75]. Taddol has also found use as a memory of chirality enhancer in the stereoselective synthesis of (i-lactams from amino acid derivatives [76, 77]. 

In addition to the consecutive aldol reactions of aldehydes, Barbas s group also reported enamine-activated Diels-Alder reactions (or double Michael reactions) between a,P-unsaturated ketones and nitroolefm (Scheme 1.15) for the first time in 2002 [17], hi contrast to MacMillan s iminium catalysis for Diels-Alder reactions, wherein a,P-unsaturated carbonyl compounds were activated as dienophiles in a LUMO-lowering strategy based on iminium formation [3], an alternative strategy involving the in situ generation of 2-amino-1,3-dienes from a,P-unsaturated ketones... 

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