Ketones, 2-amino-1 -alkenyl

There are still two other factors influencing the reactivity of ketones in the Norrish-Yang reaction. If functional groups with a relatively low oxidation potential (amino, alkenyl or aryl groups, thioethers) are present in the reactants, the excited state may be quenched by partial or complete charge transfer from these groups to the extited carbonyl group. The effects of such processes may vary from a complete loss of reactivity to an entirely new reaction mode - cyclization reactions ini-... 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

Some chiral 1,3,2-dioxastannolanes were used as catalysts in asymmetric Diels-Alder reactions of cyclopentadiene with methyl acrylate <90JCR(S)278>. A-Alkenyl- and -cycloalkenyl 1,3,2-oxaza-stannolanes, generated in situ from chiral amino alcohols, gave optically active 2-substituted aldehydes and ketones in modest to high chemical and optical yields after alkylation with methyl acrylate or acrylonitrile (which is usual for enamines) and subsequent hydrolysis <85CC504,85JOC3863>. 

Another protocol was reported by Wipf and Xu. The hydrozirconation of terminal alkynes followed by the addition of dimethylzinc forms (E)-alkenylmethylzinc (equation 18)58. The chiral amino thiol 38 has been employed as a catalyst for this reaction59. Li and Walsh found that ketones as well as aldehydes are alkenylated by alkenylzinc using the chiral catalyst 3460. 

Alkylthio)- and 2-(alkylsulfinyl)-l-alkenyl ketones (16a) and (16b) reacted with a variety of amines to give 2-amino-1-alkenyl ketones (17a) and (17b) (Scheme 10). 

Asymmetric hydrogenation of either a carbonyl or an imino group to a hydroxyl group or an amino group has frequently been employed for the introduction of chirality in amino acid syntheses. Corey s catecolborane-oxazaborolidine protocol enables transformation of difluoromethyl ketone 1 into alcohol 2 with excellent enantioselectivity. The reaction of diastereoselective amination of a-hydroxyaldehyde 3 with A,A-diallylamine and 2-furyl-boronic acid provides furyl amino alcohol 4 in good chemical yield along with excellent diastereoselectivity. This protocol is applicable for the preparation of amino acids and amino alcohols with a trifluoromethyl group by the combination of /V,/V-diallyl or N,N-dibenzyl amine and aromatic, heteroaromatic and alkenyl boronic acids [7]. The usual chemical transformations as shown in steps 5 to 8 in Scheme 9.1 lead to (2S,3R) difluorothreonine 5 [8]. 

The synthesis of 2-aminobutadienes from ketones is somewhat limited due to difficult control of /Z-stereochemistry. [27] Therefore, the catalytic aminomercuration of3-alkenyl-l-ynes 4 was a significant improvement of the synthesis of 2-amino-l,3-butadienes 5 (yields 49-75 %). [28] The catalytic aminomercuration of 4-ethoxy-3-alkenyl-1-ynes even leads to electronrich and highly reactive 1,3-diamino-1,3-butadiens which undergo a great variety of cycloadditions. [29] Scheme 2 shows the reaction for a general example (for R = H two secondary amines can add to the enine 4 to yield 6). The method can easily be extended to the preparation of chiral 2-amino-1,3-butadienes by addition of chiral amines [e. g. (5)-2-methoxymethylpyr-rolidine (SMP) [27]]. 

Aldehydes and ketones are converted to amines by a handful of methods. The most common is reductive amination. When a keto-acid or keto-ester molecule is utilized and the carbonyl is not in conjugation, reductive amination leads to an amino acid or an amino-ester. When the carbonyl of an aldehyde or ketone is P- to the carboxyl moiety, reductive amination is unnecessary for preparing amino acids and alkenyl amino acids are possible (specifically, 3-aminopropenoic acid derivatives). There are several methods that can be applied to keto-acid derivatives, largely dependent on whether the aldehyde or ketone carbonyl is in or out of conjugation with the carboxyl moiety. The first part of this section will focus on reductive amination procedures, and the latter part of the section will focus on p-keto acids and esters. A few other specialized methods for converting aldehydes and ketones to amino acids will be mentioned at the end of this section. l.l.C.1. Reductive Amination... 

There are many carbanion and ylid derivatives that also contain an acid moiety, an ester or an acid sutrogate. Ester and acid enolates, for example, react with a variety of electrophilic reagents to produce new acid or ester derivatives. If the electrophile contains an amine or an amine surrogate, amino acids are produced as the final product. In addition, ylids bearing an acid or ester moiety react with aldehydes or ketones bearing an amine moiety via a Wittig reaction or a Homer-Wadsworth-Emmons reaction to give alkenyl amino acids. 

Ylids are also convenient sources of carbanions and they react with aldehydes and ketones to give alkenes. With a suitable reactant, alkenyl amino acids can be prepared using this approach. One example used a phosphonate ester ylid in a Homer-Wadsworth-Emmons reaction 12 with amino aldehyde 1.189. The product... 

Only one example was found where this class of amino acids was produced. Oxidation of 7.246 gave a ketone and treatment with boron trifluoride led to the conjugated ketone, 7.247.132 Conjugate addition of azide, reduction to the amine and cyclization gave diastereomeric methyl 9-(3-hexyl-2-aziridino)nonanoic acid (J.248 and 7.249). The final step in that sequence proceeded in only 37% yield. If the alkenyl moiety was converted to an epoxide moiety, aziridine carboxylic acids were prepared in good yield, via the azide.132... 

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