Domino allylic alcohols

Scheme 3.34. Intermolecular domino radical addition procedure for the synthesis of silyl-protected allylic alcohols.

As shown earlier in many examples, the Claisen rearrangement of allyl vinyl ethers also provides a very powerful method for carbon-carbon bond formation in domino processes. Usually, the necessary ethers are formed in a separate step. However, both steps can be combined in a novel domino reaction developed by Buchwald and Nordmann [306]. This starts from an allylic alcohol 6/4-102 and a vinyl iodide 6/4-103, using copper iodide in the presence of the ligand 6/4-104 at 120 °C to give 6/4-105 (Scheme 6/4.25). The reaction even allows the stereoselective formation of two adjacent quaternary stereogenic centers in high yield. 

Scheme 6/4.38. Domino isomerization/aldol reaction of allylic alcohols and aldehydes using (COT)Fe(CO)3 as catalyst.

As shown in the proceeding sections, the aldol reaction - especially in a domino fashion - is one of the most suitable procedures for C-C-bond formation. Usually, one uses an enolate and a carbonyl moiety, but allylic alcohols can also be em-... 

Another domino process, designed by Polt and coworkers [16], deals with the consecutive transformation of an in situ-prepared aldehyde to give 3-amino allylic alcohols 7-31 from 3-amino acids. When the 3-amino acid ester derivative 7-29 is sequentially treated with iBu5Al2H and vinyl magnesium bromide, a 3 2 mixture of the allylic alcohol derivatives 7-30 is obtained in 60% yield, which can be hydrolyzed to give 7-31 (Scheme 7.10). 

Scheme 5 Domino isomerization-amidocarbonylation of allylic alcohols...

A broad variety of special aldehydes and ketones are easily accessible by Heck-type reactions with allylic alcohols and their homologs [3]. The potential for the synthesis of carbocydic structures is illustrated by the macrocyde 11 [4] which obviously is the product of a fourfold Heck reaction (Scheme 3). A domino process consisting of a double Heck reaction followed by an intramolecular Aldol condensation leads to the annulated ring system 15 [5]. 

These examples demonstrate that a selective Heck-Diels-Alder sequence with two different alkenes is only possible either in a stepwise manner, if an alkene reacts much faster in the Heck reaction than in the subsequent cycloaddition so that the 1,3-diene can be isolated, or as a real cascade reaction if one alkene is more reactive and thus selectively reacts as a coupling partner, whereas the other one is a better dienophile. Both concepts have been used by Kollar et al. for the annelation of cyclohexene rings onto the steroidal skeleton 26 (Scheme 4) [28-30]. At 60 °C the cycloaddition was sufficiently suppressed so that the Heck coupling product 29 could be isolated and subsequently subjected to Diels-Alder reactions with different dienophiles. For a domino reaction with both methyl acrylate and dimethyl fumarate (28) present in the reaction mixture, the conditions had to be precisely adjusted so that the mixed products 31 and 32 were formed predominantly along with only small amounts of the products of a twofold reaction of either 27 (R = CC Me) or 28 with 26. These conditions also proved suitable for a cascade reaction of 26 involving allyl alcohol 27 (R = CH2OH) or allyl acetate 27 (R = CH2OAc) and dimethyl fumarate (28). 

Quite a number of transition-metal complexes are capable of isomerizing allyUc alcohols into transition-metal-enol complexes through an internal redox process. Those can then be trapped in situ with aldehydes in an aldol reaction. Motherwell and coworkers developed a RhClIPPhjIj-catalyzed domino isomerization-aldol reaction of secondary allyl alcohols, which gave rise to a mixture of syn- and owti-aldol products, with only small amounts of the regioisomeric aldol product occasionally being formed (Scheme 8.25) [42]. 

Table 8.11 Domino isomerization/aldol reaction of allyl alcohols [45].

Since oxidation and reduction reactions can provide many organic compounds with reactive functional groups such as aldehydes, ketones, enones, amines, alcohol, allylic alcohols, and so on, further transformations can easily be added to give a domino process. Depending upon the position of the oxidation or reduction reaction in the domino process, this chapter is divided into three classes first, the domino reaction is initiated by an oxidation or reduction reaction second, the domino reaction has the oxidation or reduction step in the middle and third, the domino reaction is terminated by an oxidation or reduction reaction. Most of the oxidation and reduction reactions come under the category of anionic domino process, as they provide nucleophilic or electrophihc functionalities and only very few oxidation and reduction reactions proceed with cationic domino process. 

Thus, oxidation of the allylic alcohol 363 to the corresponding aldehyde in the presence of a large excess of manganese dioxide initiated the domino oxidation/Diels-Alder/hetero-Diels-Alder sequence. After formation of 366 via an endo-E-syn transition state, the terminal aldehyde 367 then gave the tetracycle 364 in the concluding hetero-Diels-Alder step in 28% yield after 2 days. Intermediate 364 was then further transformed into the natural product 365 in an additional 14 steps, featuring an intramolecular Heck reaction and an iridium-catalyzed isomerization. 

The idea enabled a domino process by combining copper-catalyzed C-O bond formation and thermal Claisen rearrangement. Subjecting allylic alcohol and vinyl iodide to the reaction conditions led to the clean formation of the desired rearrangement product in 55% yield with high stereochemical purity (Eq. 3.1.15). The preparation of two adjacent quartemary stereocenters from geraniols is successfully prepared using the aforementioned reaction conditions (Eq. 3.1.16). 

Allylic alcohols RCH=CHCH20H can get engaged in a triple-domino process, commencing with oxidation to RCH=CHCH=0, catalysed by the Fe complex (255), followed by iminium formation with the prolinol catalyst (256a), addition of a cyclic... 

Treatment of homo-allylic alcohols with catalytic MTO and hydrogen peroxide results in epoxidation followed by hydroxyl lactonization to yield substituted tetrahydrofurans in high yield (eq 14). Alcohols, acids and esters all undergo such domino epoxidation/cyclization reactions. ... 

An interesting palladium-catalyzed cascade reaction leading to 3,3-disubstituted oxindoles 190 starting from 2-(alkynyl)aryl isocyanates 189 with benzylic alcohols has been developed by Toyoshima et al. [76] (Scheme 6.53). This reaction integrates a cyclization step and a novel [1,3] rearrangement step. Both benzylic and allylic alcohols could be introduced efficiently to this domino process. Furthermore, the products of this reaction are an important class of heterocycles which are often found in naturally occurring and biologically active molecules. 

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