Reduction hydroacylation

Alkene-C=X (X=0, NR) Coupling (Reductive Carbonyl-Ene and Reductive Hydroacylation)... 

A potential liability associated with such reductive hydroacylations resides in the fact that only one acyl residue of the symmetric anhydride is incorporated into the coupling product. For more precious carboxylic acids, selective acyl transfer from mixed anhydrides is possible. Mixed anhydrides derived from pivalic acid are especially convenient, as they may be isolated chromato-graphically in most cases. In practice, mixed anhydrides of this type enable completely branch-selective hydroacylation with selective delivery of the aromatic and a,()-unsalurated acyl donors (Scheme 19). 

Scheme 19 Selective acyl transfer in reductive hydroacylations involving mixed carboxylic anhydrides derived from pivalic acid...

Alkylzirconocene thiolates, preparation, 4, 932 Alkynals, reductive cyclization, 10, 527 5-Alkynals, hydroacylation-isomerization, 10, 93 ]1 ]2-Alkyne-alkylidenes, in Ru and Os half-sandwiches,... 

The hydroacylation of olefins with aldehydes is one of the most promising transformations using a transition metal-catalyzed C-H bond activation process [1-4]. It is, furthermore, a potentially environmentally-friendly reaction because the resulting ketones are made from the whole atoms of reactants (aldehydes and olefins), i.e. it is atom-economic [5]. A key intermediate in hydroacylation is a acyl metal hydride generated from the oxidative addition of a transition metal into the C-H bond of the aldehyde. This intermediate can undergo the hydrometalation ofthe olefin followed by reductive elimination to give a ketone or the undesired decarbonyla-tion, driven by the stability of a metal carbonyl complex as outlined in Scheme 1. 

The addition of a catalytic amount of Cp2TiCl2 dramatically increases the yield of the hydroacylated ketone formed in the hydroacylation of 1-alkenes with heteroaromatic aldehydes by using Wilkinson s complex and 2-amino-3-picoline as co-catalysts.1264 Cp2TiCl2 catalyzes the reduction of aryl halides by sodium borohydride. The reaction scope and mechanism are solvent dependent.1265... 

Ruthenium-catalyzed hydroacylation of 1,3-dienes with aromatic and heteroaromatic aldehydes occurs in relatively good yields to afford the corresponding fi, /-unsaturated ketones . Isoprene and benzaldehyde were treated with 4 mol% Ru(COD)(COT) (COD = 1,5-cyclooctadiene, COT = 1,3,5-cyclooctatriene) and 4 mol% PPhs under argon for 40 hours to give 54% 80 (equation 41). The key intermediate is an acyl- ) -(allyl)ruthenium complex which undergoes reductive elimination to give the corresponding... 

Transition metal catalyzed asymmetric hydrocarboration reactions are addition reactions forming one C—C and one C—H bond. Prominent examples are hydrovinylation, hydroformylation, hydroacylation, hydrocarboxylation, and hydrocyanation. Various related conversions, such as hydroalkylation, hydroarylation, conjugate addition, reductive dimerization, and metal induced ene reactions are collected in Section 1.5.8.2.6. dealing with miscellaneous methods of this type. Some of these methods are not exclusively mediated by metal catalysts and therefore are also covered in other sections of this volume. 

The method of transition metal induced hydroacylation of olefins with aldehydes has its origins in the observation that aldehydes are decarbonylated by Wilkinson s catalyst31. Mechanistically, decarbonylation is believed to start with an oxidative addition of a low valent transition metal unit to the aldehyde C —H bond. This individual step has been observed in several cases32 " 37. The resulting metal acyl hydride system can then be decarbonylated to form a new C - H bond upon reductive elimination, steps which are also well known. 

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. 

A similar intramolecular hydroacylation is possible via reductive radical aldehyde addition to alkencs and subsequent oxidation of the resulting alcohol. Based on this observation a strategy towards the synthesis of cuparenoids [( )-a-cuparenone. ( )-epilaurene and laurene] was... 

An insertion-reductive elimination sequence is involved in the rhodium-catalyzed, intramolecular hydroacylation of 4-alkenals to form cyclopentanes ... 

More recently, Yang and Yoshikai demonstrated a Co-catalyzed enantioselective intramolecular hydroacylation of ortho vinyl-substituted benzal-dehydes. Upon further screening of Co precatalysts and reductants, they identified the combination of C0CI2 (10 mol%), (R,R)-BDPP (10 mol%), and... 

Besides the Rh catalysts that were employed in enantioselective intramolecular hydroacylation reactions of ketones extensively, Yang and Yoshikai reported that the Co-(i ,i )-Ph-BPE complex (10 mol%), in combination with In powder (20 mol%) as the reductant, was able to promote intramolecular hydroacylation reactions of 2-acylbenzaldehyde derivatives to afford enantio-enriched phthalides in up to 97% yield and 98% ee (Scheme 8.31). ... 

The combination of Ni(COD)2 and l,3-di-ferf-butylimidazol-2-ylidene (ItBu) was demonstrated to effectively catalyse an intramolecular alkene hydroacylation to construct five- and six-membered benzocyclic ketones in good to excellent yields (Scheme 14.71). Al-aryl-substituted NHCs are not effective for this transformation. The reaction is proposed to proceed via a process as shown in Scheme 14.72. Thus, 2-allylbenzaldehyde coordinates to Ni(0)/ItBu to form complex A. The oxidative cyclisation of A gives a nickelacycle intermediate B. B undergoes p-hydride elimination and reductive elimination to produce final product C, along with regeneration of the catalyst. ... 

A simple catalytic cycle for hydroacylation is shown in part A of Scheme 18.19. Hydroacylation occurs by oxidative addition of the formyl C-H bond to generate an acyl hydride complex. Insertion of olefin into the metal hydride then generates an alkyl acyl intermediate. These complexes undergo reductive elimination, as described in Chapter 8. Although these basic steps constitute the catalytic cycle, many other processes occur outside of this cycle in the catalytic system. Some of these steps lying off the cycle lead to poisoning of the catalyst and others are unproductive reversible processes that have been revealed by H/D exchange experiments. Part B of Scheme 18.19 shows a catalytic cycle that includes these side processes. 

In 2014, Yang and Yoshikai reported enantioselective intramolecular hydroacylation reactions of ketones and olefins using cobalt-chiral diphosphine catalysts (Scheme 10.7) [21]. A cobalt catalyst generated by the reduction of CoBr2 with indium powder in the presence of l,2-bis((2R,5R)-2,5-diphenylphospholano)ethane ((R,R)-Ph-BPE) promotes cyclization of a variety of 2-acylbenzaldehydes to afford phthalide derivatives in moderate... 

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