Allylic substitution Mitsunobu reaction

The RRM precursor was synthesised in a multistep procedure from alcohol 33. The first allyl amino side chain was introduced by a Mitsunobu reaction with Ns protected allylamine with inversion of configuration. Attempts to introduce the second N-protected allylamine via an 7 -allyl Pd(0)-substitution failed. Changing the order of the substitution was also unsuccessful (Scheme 11). 

Several examples of reactions of allyl alcohols under Mitsunobu reaction conditions using diethyl azodicarboxylate (DEAD) and triphenyl phosphine giving allyl amines are known. An example is the reaction of the steroid 5 with azide nucleophiles under Mitsunobu reaction conditions, giving the corresponding azide 6 in 63 % yield (Eq. (3)) [5]. The reaction is regioselective with inversion of the configuration and no SN2/ substitution is observed. 

The Mitsunobu reaction is one of the staple reactions for clean nucleophilic substitution with inversion of configuration. It came as a surprise, therefore, to find that a Mitsunobu reaction on allylic alcohol 143.1 [Scheme 8.143] using rerr-butyl 2-(trimethylsilyl)ethylsulfonylcarbamate (143.2) as the nucleophile occurred with retention of configuration. o unusual stereochemistry was explained by a double inversion process in which neighbouring group participation first leads to the intermediate 1433. A subsequent second nucleophilic substitution by 1433 then gave the product 143.4 in 86% yield. 

The first synthesis of the tetracyclic substructure ABCE was published by Hart et al. As illustrated in Scheme 26, the route includes (a) a new approach to substituted perhydroisoquinolines that features a stereoselective free radical allylation, (b) a Mitsunobu reaction using a new iV-acylsulfonamide (this step was completed with net retention of configuration), and (c) final preparation of a A. -azocine via an intramolecular iV-alkylation in high yield (the system has limited degrees of freedom due to the presence of the Z-alkene) [88]. 

Another possibility for substituting flie hydroxyl group by a nucleophile is the Mitsunobu reaction (31,32). In this case, the alcohol is linked to the nucleophile using diethyl azodicarboxylate (DEAD) and Iriphenylphosphine. This reaction was applied to the allylic alcohols [5a,b] (from mefliyl oleate) (Eq. 13, Table 3) and [2] (from methyl 10-undecenoate) (Eq. 14, Table 4). 

In some cases, allyl substituted alcohols react via an Sn2 or Sn2 mechanism under the standard Mitsunobu reaction conditions. Benzyllic alcohol 93, for example, gave the isomeric ethers 94 and 95 in a 3.8 to 1 ratio. ... 

Sulfonyloxynitriles derived from cyanohydrins of aromatic aldehydes react with weak nucleophiles, e.g., KOAc, with partial racemization [56] (Scheme 14, R = Ph). The Mitsunobu reaction represents an alternative to the O activation of cyanohydrins combined with nucleophilic substitution [57]. Mitsunobu conditions work especially well in the exchange of allylic and benzylic hydroxyl groups in cyanohydrins [57b]. 

The first step consisted of the Mitsunobu etherification of an allyl alcohol with the resorcinol monoester, which afforded 102. Cleavage of the benzoyl protecting group released the phenol, which was then attached to the solid support. One-step cleavage of the THP group and bromination was achieved with PPhs/C Br4 to furnish 103. Nucleophilic substitution of the bromide with benzylamine was followed by acylation of the secondary amine wtith N-Boc-allylglycine 104, which resulted in the precursor 105, ready for the metathesis reaction this was performed with catalyst 101 to yield the final product 106. Either 1-octene or ethene was employed to generate 101. 

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