Alkenyl boronate aldehyde

Additionally, the protocol proved not only applicable to aryl-substituted organo-metallics, but also enabled the use of an alkenyl boronic acid. Further, aldimine 11 was regioselectively arylated with this catalytic system, yielding-after subsequent hydrolysis-aldehyde 12 (Scheme 9.6) [17]. 

The synthesis of a-imino aldehydes through the thermal [l,3]-rearrangement of 0-alkenyl benzophenone oximes has been reported. A copper-mediated C-O bond coupling between benzophenone oxime and alkenyl boronic acids provides access to 0-alkenyl oximes and a Horner-Wadsworth-Emmons olefination applied to the a-imino aldehyde products gives y-imino-a, -unsaturated esters (Scheme 166). ... 

In the mid 1990s Petasis reported three-component coupling reactions of boronic acids, amines, and aldehydes as a general approach to optically active secondary amines. Alkenyl boronic acids were shown conveniently to undergo addition to iminium ions formed in situ under mild conditions from amines and aldehydes (Scheme 11.9) [65]. For example, a mixture consisting of vinylboronic acid 64, (S)-2-phenylglycinol (65), and aldehyde 66 furnishes 67 in 78 % yield and >99 1 dr. 

Danishefsky has developed a mild oxidative procedure for the conversion of highly functionalized alkenyl boronates (obtained by alkenyl boronate cross-metathesis) to the corresponding aldehydes with trimethylamine N-oxide that was found to be compatible with hydroxyl, ketone and acid functionalities present in alkenyl boronates without protection [109]. For example, by using this methodology, it was possible to oxidize the iodoalkenyl boronate intermediate 133 to the aldehyde 134 that was subjected to intramolecular Nozaki-Kishi macrocyclization yielding 11-hy-droxy deoxyepothilone precursor 135 in 40% yield (Scheme 3.71). 

Some authors have described the generation of boronates and stannanes bound to a support starting from the corresponding aryl haHdes [372, 6]. Boranes, boronic esters, and stannanes can furthermore be readily obtained from vinyl halides or from alkenes or alkynes by means of hydroboration or hydrostannylation (see Section 4.2). Boronates and silanes or stannanes can act as carbanion equivalents. Thus, support-bound boronates can release aryl alkenyl groups upon transmetala-tion to Rh. The intermediately formed Rh species can act as nucleophiles, and react with aldehydes to give alcohols (618) or can perform Michael additions (621, 622) [437, 438, 439] (Scheme 129) (see also Sections 4.7.15 and 4.2). 

Under basic conditions, Pd(II) catalyses the bisfunctionalisation of allenyl esters by boronic acids and aldehydes in a one-pot reaction which yields 4,6-disubstituted 5,6-dihydropyran-2-ones 20. The tandem process involves attack by nucleophiles at the 3-position and by electrophiles at C-4 some uncyclised 5-hydroxypent-2-enoic acid derivatives can also be recovered <05JOC6848>. The aerobic cyclisation of O-alkenyl P-ketoamides affords 2,6-dihydropyran-3-ones (Scheme 7) <05OL5717>. 

E)-a,p-Unsaturated aldehydes. The anion of 2-alkenyl N,N-diethyldithio-carbamates (2) reacts with (1) at the a-carbon atom to form a product (a) that undergoes facile [3,3] sigmatropic rearrangement to form (3). The products are hydrolyzed to aldehydes (4) by red mercuric oxide and boron trifluoride etherate (3,136). ... 

Intramolecular cyclisation of the aldehyde 40 with boron trifluoride etherate gave the oxepane 41 <97JOC7439>. The stereochemistry of the product is indeptendent of whether an E or a Z alkenyl group is involved in the cyclisation, although yields are higher when the E isomer is used (79%). The bicyclooxepane 43, obtained in four steps from the epoxide 42, is readily converted into the tricyclic system 44 <97TL5853>... 

Other approaches to trisubstituted aikenes via organoboranes involve alkynyltrialkyl borates, alkenyltrialkyl borates or the cross-coupling reaction of alkenylboronic acids with alkyl halides. Both ( )- and (2)-l,2-disubstituted alkenyl bromides can also be prepared by the methodology shown in eq 7. The boron trifiuoride etherate-mediated 1,4-addition of 1,2-disubstituted alkenylboronates affords y,5-unsaturated ketones (eq 9). The boronates can also be converted into chiral enoiborates for the enantioselective addition to aldehydes. ... 

Subsequent to this, there have been numerous reports of the use of this reaction using alkenyl, alkynyl and arylboronic adds or esters in reactions with a range of amines and aldehydes. This reaction has been variously named the boronic Acid Mannich , boronic Mannich , boro-Mannich , Petasis boronic acid-Mannich , Petasis borono-Mannich , and Petasis" reaction. The more indusive term of Petasis borono-Mannich reaction will be used throughout this chapter. 

Finn and Petasis have independently shown that salicylaldehyde is a suitable aldehyde for the Petasis borono-Mannich reaction, with alkenyl, aryl and heteroaryl-boronic acids (Equation 6) [30, 31]. The reaction works best for aliphatic secondary amines, as in the formation of 41 primary amines give modest yields of adducts 41. Benzaldehydes lacking ortho hydroxyl functionality do not react, with even ortho methoxy functionality being unsuitable, which is consistent with a tethering mechanism via putative intermediate 9 (Figure 7.3). Petasis and Boral reported that reactions occurred at room temperature over 24-36 h, using EtOH, MeOH or acetonitrile. 

The pyrrolizidine natural products can be obtained by exploitation of the Petasis MCR for combining aldehydes, amines, and vinylboronic acids, as shown by Pyne and coworkers in 2008 [35]. Application of aldopentoses yields polyhydroxylated allyl amines, that provides opportunity for further derivatization to, for example, uniflorines. The MCR commences by boronate-assisted imine formation and protonation (111). Subsequent alkenyl transfer from the borate to the protonated imine delivers the secondary allyl amine 116 in excellent diastereoselectivity (Scheme 14.14). 

Enol stannanes of cyclohexanone and propiophenone have been indicated to take part in r/treo-selective aldol reactions with benzaldehyde at low temperatures e.g. —78 °C), but to be erythro-seAsciiwe at higher temperatures ca 45 °C). Two complementary methods have been described for stereoselection in aldol-type reactions. Whilst a-mercurio-ketones show eryr/wo-selection in their reactions with aldehydes in the presence of boron trifluoride diethyl etherate, pre-formed lithium enolates and aldehydes, in the presence of simple trialkyl-boranes, lead to mixtures that are rich in the more stable threo-d do product. Aldol-type products arise from 1,3-alkyl migrations of alk-l-enyl alkyl acetals and ketals, in a reaction that is catalysed by boron trifluoride diethyl etherate (Scheme 52). Diastereoselection is possible, since (.E)-alkenyl acetals give the... 

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