Annulation reaction determining products

Tsuji and co-workers completed a total synthesis of (+)-19-nortestosterone by using a key intermediate prepared using the Hajos-Wiechert reaction of 40 with stoichiometric (S)-phenylalanine following the Wiechert protocol. This approach was the best among approximately twenty conditions that were tried the resulting product 41 was oxidized to the known crystalline compound 42 to determine that the Hajos-Wiechert reaction occurred in 76% ee. A series of alkylation and annulation reactions was used to convert 42 into (+)-19-nortestosterone (43). 

The most common citation of rj4-vinylketene complexes in the literature is to be found in mechanistic discussions of the Dotz annulation.8 In the years since the reaction was discovered,2 there has been an enormous amount of research conducted to determine a definitive mechanism. Nevertheless, certain transformations in the mechanism are still open to speculation, the most recent reassessment having been postulated by Sola.911 is not within the scope of this review to comprehensively discuss a subject which has been extensively covered elsewhere.8,10,11 However, the reactions of i74-vinylketene complexes of chromium, and indeed of all the other metals in this review, are so intrinsically linked with the Dotz annulation that we must acquaint ourselves with its intricacies. We shall see the same structures occurring in mechanisms time after time, and the same classes of organic molecules being isolated as final products. 

The concurrent formation of two rings by chromium catalysis is demonstrate in Scheme 6 <95TL3027>. Conversion of the hydrazone (48) into the complex (49) and subsequent reaction with hex-6-yn-l-ol affords the annulated complex (50) which is decomplexed by irradiation in benzene. The stereochemistry of the intermediate complex (50) was determined by recomplexation of the final product (51), which gave a separable mixture of the two possible diastereoisomers. 

In addition to the reaction coordinate mapped out by the DRC, the minimum energy path from transition state to reactants or products is of interest. As with the DRC originating at the transition state, this path is coordinate-system independent. The calculation to determine the minimum energy path starts in a similar manner to the DRC calculation, only after the initial displacement, all velocities are annulled at every step. This results in the system moving perpendicular to the energy contours in mass-weighted coor nate space. Sutime independent, and are called intrinsic reaction coordinates (IRC). For a review of potential energy surfaces for polyatomic reaction dynamics, see ref. 59. 

A Robinson annulation is comprised of a Michael reaction, followed by an intramolecular aldol condensation. To determine the starting materials necessary to prepare the desired product via a Robinson annulation, we draw the following retro synthetic analysis ... 

---