Hydroacylation intramolecular

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

Two years later, Bosnich described an extensive study of asymmetric rhodium-catalyzed intramolecular hydroacylation reactions [16]. Like Sakai, Bosnich found that Rh(l)/ BINAP is an unusually effective catalyst for this process, furnishing excellent enantioselectivity for a range of substrates (Eq. 13). Bosnich also reported thaL if the R substituent is a relatively unhindered alkyl (for example. Me) or an aromatic group, lower (< 80% ee) enantioselectivity is observed. 

Since the early 1990s, considerable progress has been achieved in the development of catalytic enantioselective intramolecular hydroacylation reactions of alkenes/alkynes that generate five-membered rings. Nonetheless, the vast majority of interesting hydroacylation reactions has not yet proven susceptible to effective asymmetric catalysis. This deficiency represents an exciting opportunity for future investigations in this... 

Scheme 13 Rh-catalyzed intramolecular hydroacylation route to carbocycles.49...

Intramolecular hydroacylation, on the other hand, is an attractive catalytic process because it produces cyclic ketones. Furthermore, with appropriate chiral phosphine ligands, this reaction could convert prochiral 4-pentenals into chiral cyclopentanones (Scheme 5) [14]. 

C-H Transformation at Aldehydes and Imines Table 1. Examples for inter- and intramolecular hydroacylation. 

A primary alcohol and amines can be used as an aldehyde precursor, because it can be oxidized by transfer hydrogenation. For example, the reaction of benzyl alcohol with excess olefin afforded the corresponding ketone in good yield in the presence of Rh complex and 2-amino-4-picoline [18]. Similarly, primary amines, which were transformed into imines by dehydrogenation, were also employed as a substrate instead of aldehydes [19]. Although various terminal olefins, alkynes [20], and even dienes [21] have been commonly used as a reaction partner in hydroiminoacylation reactions, internal olefins were ineffective. Recently, methyl sulfide-substituted aldehydes were successfully applied to the intermolecu-lar hydroacylation reaction [22], Also in the intramolecular hydroacylation, extension of substrates such as cyclopropane-substituted 4-enal [23], 4-alkynal [24], and 4,6-dienal [25] has been developed (Table 1). 

Inter- and Intramolecular Hydroacylation 303 Chul-HoJun and Youngjun Park... 

Two different reports have illustrated that cationic Me-DuPhos-Rh complexes serve as excellent catalysts for asymmetric C-C bond-forming cyclization reactions. In the first example, Bosnich and co-workers discovered that valuable 3-substituted cyclopentanones can be prepared simply by treatment of 4-pentenal derivatives 68 with the Me-DuPhos-Rh catalyst.69 Asymmetric intramolecular hydroacylation furnished the product cyclopentanones 69 in high yield and with enantioselectivities ranging from 93% to 98% (Scheme 13.24). 

Lenges CP, Brookhart M. Co(I)-catalyzed inter- and intramolecular hydroacylation of olefins with aromatic aldehydes. J Am Chem Soc 1997 119(13) 3165—3166. 

Asymmetric epoxidation is applied to the synthesis of the novel ferroelectric liquid crystals 99 that have the chiral trans-2, >-e, o y hexyl group as a core moiety (Scheme 31). The (25, 35 )-epoxy alcohol 98, conveniently obtained in 86% ee, is transformed into the desired material in two steps [99]. A formal synthesis of Brefeldin A (102), which shows a variety of biological activity represented by antitumor, antifungal, and antiviral activity, is accomplished via a highly enantioselective intramolecular hydroacylation of racemic pentanal 100 with 0.9 % of cationic Rh[(S)-binap] BF4. A 1 1 mixture of trans- and cis-cyclopentanones 101 is obtained with a high enantiomeric excess of 96% for each (Scheme 32). In the following step, the undesired cw-isomer is converted into the thermodynamically favored tran -isomer for further transformation [100]. 

Mechanistic studies on the intramolecular hydroacylation by using deuterium-labeling experiments have been reported by several groups [95-100]. The results of their studies showed that the addition of the Rh-H bond to a carbon-carbon double bond takes place in syn fashion [95,96]. They also demonstrated that C-H bond cleavage, hydrid transfer to the double bond, and carbonyl deinsertion are all fast and reversible steps (Scheme 3) [99]. 

James et al. have applied this intramolecular hydroacylation to the resolution of racemic enals using rhodium(I) complex and chiraphos [103]. In this case, 5-membered ring ketones with up to 69% ee of the optical isomer are obtained in moderate yields (15-58% yields) (Eq.48). 

This reaction competes with intramolecular hydroacylation of pent-4-enals to form cyclopen-tanones. In the case of exo- and ent/o-norborn-5-ene-2-carboxaldehyde (4) if treated with Wilkinson s catalyst [tris(triphenylphosphane)rhodium(I) chloride] only decarbonylation occurs. While the exo-aldehyde exo-4 leads to norbornadiene (5), the e fi o-aldehyde endo-4 reacts to form nortricyclene (6 tricyclo[2.2.1.0 ]heptane). These results support organometallic pathways and exclude radical intermediates, since here identical products should be formed. 

Hoffman and Carreira [31] reported a Rh-catalyzed asymmetric intramolecular hydroacylation of pent-4-enal substrates, providing P-substituted cyclopentanones in good yield and excellent selectivity by using chiral spiro phosphoramidite-alkene ligand (R)-29 (Scheme 29). 

Intramolecular hydroacylation of 4-substituted pent-4-enals is catalyzed by Rh (I) complexes and leads to 3-substituted cyclopentanones. When the ligand of rhodium is (l ,2,S)-3.35 (X = CH2CH2) or even better (Ky or (S)-binap 3.43 (Ar = Ph), cycloalkanones are obtained with an excellent enantiomeric excess... 

The presence of the hydride acyl intermediate in decarbonylation suggests the possibility of alkene insertion into the metal hydride bond and reductive elimination of a ketone. This was first observed in the intramolecular hydroacylation of 2,3-disubstituted 4-pcntcnals using stoichiometric amounts of Wilkinson s catalyst or in the presence of tin(IV) chloride to give substituted cyclopentanones and stereoisomeric cyclopropanes as side products27. 

On the contrary [Rh(acac)(C2II4)2] and unsaturated aldehydes, such as 4-pentenal and 4-hexenal, add intcrmolecularly to ethene to form acyclic ketones40. Thus, hydroacylation of ethene with 4-pentenal gives three 5-oxoheptene isomers. The aldehyde double bond in the substrate is essential, since saturated aldehydes do not react, and without ethene no intramolecular hydroacylation is observed with unsaturated aldehydes40. 

Stereoselectivity in the Intramolecular Hydroacylating Ring Closure of Unsaturated Aldehydes... 

Hydroacylation is especially interesting in its intramolecular version, converting unsaturated aldehydes to cyclopentanones. Numerous examples of transition metal catalyzed hydroacylations have been described, mostly with 4-alkenals of various substitution patterns. The reaction is used for the construction of starting materials in prostaglandin synthesis and the preparation of other cyclopentanoid systems. Rhodium catalysts, mainly of the Wilkinson type, are used. The steric course of hydroacylation is believed to occur in a m-addition manner. This was deduced from results of intermolecular alkyne hydroacylation56 (vide supra) and the intramolecular hydroacylation of deuterated E- and Z-isomers of 7,5-unsaturated aldehydes39-5 . 

Similarly, an optically active substituted 4-pentenal [obtained from ( + )-limonene by oxidative ring cleavage] upon intramolecular hydroacylation with Wilkinson s rhodium complex stereoselectively gives a precursor for prostanoic acid and 8-isoprostanoic acid69. 

Synthesis of a precursor of 11-deoxyprostaglandin is achieved via stereoselective intramolecular hydroacylation of the 4-pentenal derived from (—)-limonen-10-ol7°. 

Another application of stereoselective intramolecular hydroacylation to natural product synthesis, starting from (-t-)-limonen-lO-ol, leads to the bicyclo[3.3.0]octane skeleton and a synthesis of the key intermediate for carbacyclin71. 

A further application of stereoselective intramolecular hydroacylation in natural product synthesis starting from (—)-limonene leads to nepetalactonc, an iridoid-type pheromone72. 

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