Hydroformylation intramolecular

The aldol reaction is probably one of the most important reactions in organic synthesis. In many industrially important hydroformylation processes selfcondensation of aldehydes is observed. Sometimes this consecutive reaction is favored as in the production of 2-ethyl hexanol. But synthetic applications of tandem hydroformylation/aldol reactions seem to be limited due regiose-lectivity problems of a mixed aldol reaction (Scheme 28). However, various tandem hydroformylation/intramolecular mixed aldol reactions have been described. 

Figure 29. Hydroformylation-intramolecular acetalization of allylic alcohols...

Figure 30. Different allylic alcohols studied in hydroformylation-intramolecular acetalization...

Scheme 5-70 Hydroformylation-intramolecular cyclization to hemiacetals and hemiaminals and some subsequent transformations.

Risi and Burke [29, 30] synthesized (+)-patulolide C, which is a macrocyhc compound isolated from a Penicillium urticae mutant via an asymmetric sequential hydroformylation-(intramolecular Wittig olefination) reaction applying... 

The reverse reaction (formation of metal alkyls by addition of alkenes to M-H) is the basis of several important catalytic reactions such as alkene hydrogenation, hydroformylation, hydroboration, and isomerization. A good example of decomposition by y3-elimination is the first-order intramolecular reaction ... 

In a similar fashion, allylboronates can be used as allylation reagents under hydroformylation conditions. Thus condensed 1,5-oxazadecalin systems are achieved via tandem hydroformylation/allylboration/hydroformylation sequences starting from an N-allyl-y-amidoallylboronate (Scheme 23) [77,78]. The aldehyde obtained from a regioselective hydroformylation undergoes diastereoselective intramolecular allylboration to give an intermediate al-lylic alcohol derivative. The reaction does not stop at this stage, since this... 

Thus /i-carbolincs can be obtained in a tandem hydroformylation/Pictet-Spengler-type intramolecular electrophilic aromatic substitution of polymer bound olefins (Scheme 26) [80]. 

In a similar fashion, hydroformylation of N-allyl-pyrrols leads to 5,6-dihydroindolizines via a one-pot hydroformylation/cyclization/dehydration process (Scheme 27) [81,82]. The cyclization step represents an intramolecular electrophilic aromatic substitution in a-position of the pyrrole ring. This procedure was expanded to various substrates bearing substituents in the al-lyl and in the pyrrole unit. 

A tandem hydroformylation/carbonyl ene reaction can be observed in cases, in which substrates with at least two isolated oleftnic bonds are hydro-formylated at only one double bond selectively. Thus hydroformylation of limonene with PtCkCPPlH /SnCk/PPlH or PtCl2(diphosphine)/SnCl2/PPh3 gives a mixture of two diastereomeric alcohols upon carbonyl ene reaction of the intermediate aldehyde, (Scheme 36). Best results are achieved with a PtC Cdppb) complex. The mechanism of the final intramolecular cycli-zation step resembles an acid catalyzed carbonyl ene reaction [89]. 

Ojima and coworkers have developed a similar approach to the synthesis of piperidine and related ring systems, which they describe as cyclohydrocarbonylation. In this approach, carbamate-protected allylglydnes (for example, 32) are subjected to rho-dium(I)-catalyzed hydroformylation in an alcohol solvent (Scheme 5.13) [17]. 6-Alkoxy-pipecolates 33 are isolated in good yield and were shown to be amenable to further stereoselective transformations. This methodology has recently been expanded to include fully intramolecular variants that can form two rings in a single reaction. Thus, alkenes 34 are subjected to the cyclohydrocarbonylation conditions to provide azabicy-clo[4.4.0]aUcane amino acids 35 which can serve as conformationaUy restricted dipeptide surrogates and /9-turn mimetics [18]. 

Hydroformylation reactions have been shown to be amenable to use in tandem or domino reaction sequences. In one elegant example, alkene 36 was subjected to rho-dium(I)-catalyzed hydroformylation, and the resulting aldehyde underwent smooth intramolecular allylboration (Scheme 5.14) [19]. This produced a new terminal alkene which underwent a second hydroformylation to provide, after workup,lactols 37 in 80% yield and with excellent diastereoselectivity. 

Intramolecular Allylboration. In one rare but impressive example involving a masked aldehyde, a domino hydroformylation/allylboration/hydroformyla-tion reaction cascade has been designed to generate bicyclic annulated... 

Auto-tandem hydroformylation-cyclization, catalyzed by [RhCl(cod)]2, enables expansion of the organic skeleton of unsaturated silyl enol ethers (Scheme 10). Linear aldehydes generated in the hydroformylation step subsequently undergo Rh-catalyzed, intramolecular Mukaiyama aldol addition. Bicyclic ketones are also accessible from cyclic silyl enol ethers. 

A quinazoline alkaloid skeleton has been synthesized by means of the Rh-catalyzed cyclohydrocarbonylation of diaminoalkenes. The reaction of 2-(A -allylaminomethyl)aniline 55 gave quinazoline 59 in excellent yield through the highly linear-selective hydroformylation of 55 to aldehyde 56, followed by the sequential formations of hemiaminal 57 and iminium ion 58 as intermediates and then the subsequent intramolecular amine addition (Scheme In the same manner, the reaction of A -allyl-2-aminomethylaniline 60 afforded 61 in 96% yield. ... 

---