Michael–Michael Ring-Closure Reactions for a Dihapto-Coordinated Naphthalene Complex of Molybdenum

Abstract

The complex MoTp­(NO)­(DMAP)­(η2-naphthalene) (1; DMAP = 4-(dimethylamino)­pyridine; Tp = tris­(pyrazolyl)­borate) is demonstrated to undergo Michael–Michael ring-closure (MIMIRC) reactions promoted by trimethylsilyltriflate. The resulting hexahydrophenanthrenes are formed stereoselectively, with isolation of a single dominant isomer. Combining the MIMIRC sequence with an oxidative decomplexation step, the final tricyclics can be synthesized from the naphthalene complex with overall yields between 19 and 50% (for four steps). This reaction sequence is shown to be capable of producing a steroidal core directly from naphthalene, providing access to a biologically relevant carbon framework.

Structural Analysis of the Michael-Michael Ring Closure (MIMIRC) Reaction Products

“…Assuming that thermodynamic equilibrium is reached in the formation of the eight diastereomeric alkoxides, it would be possible to estimate the ratio in which these compounds would be obtained from their relative stabilities. Table 3 shows the relative population (%) for the two most stable conformers of diastereoisomers 2a (20%), 2n (~3%) and 2m (~77%) obtained from the Boltzmann distribution law at 25 • C. As can be seen, the expected population of decalin 2m (~77%) is close to the experimental yield (79%) previously described [15]; however, other experimental results reveal the presence of decalins 2a (43%, this work) and 2n (36%) [18]. This behavior may be due to subtle variations in reaction conditions carried out by each research group, which likely influence some step of the cascade reaction.…”

“…In particular, it appears that the preparation of decalin derivatives by Michael-Michael ring closure (MIMIRC) double addition [10,11] has partially been overlooked due to the large number of novel synthetic alternatives that were developed for the same purpose in the last 20 years [12][13][14][15][16]. However, since the pioneering work of Posner and colleagues [10,11], the synthetic value of this protocol due to its high convergence, atom economy and simplicity of the reaction conditions has been demonstrated, thus remaining as a competitive alternative to produce decalins with a rich assortment of functional groups.…”

“…However, since the pioneering work of Posner and colleagues [10,11], the synthetic value of this protocol due to its high convergence, atom economy and simplicity of the reaction conditions has been demonstrated, thus remaining as a competitive alternative to produce decalins with a rich assortment of functional groups. In particular, it appears that the preparation of decalin derivatives by Michae chael ring closure (MIMIRC) double addition [10,11] has partially been overlooked d the large number of novel synthetic alternatives that were developed for the same pu in the last 20 years [12][13][14][15][16]. However, since the pioneering work of Posner and collea [10,11], the synthetic value of this protocol due to its high convergence, atom econ and simplicity of the reaction conditions has been demonstrated, thus remaining as a petitive alternative to produce decalins with a rich assortment of functional groups.…”

Asymmetric organic synthesis with stoichiometric transition metal complexes

“…The most impressive achievement of the dearomatization methodology in terms of the complexity of bond-formation is the racemic synthesis of the complete steroidal core by a Michael-Michael ring closure reaction of the molybdenum complex with   -coordinated naphthalene (Scheme 33). 59 The protocol was performed as a one-pot operation providing the organic product as a single stereoisomer in an overall 13% yield.…”