Cyclohexenones trisubstituted

These iron complexes can be used to effect a stereocontrolled synthesis of 4,4,5-trisubstituted cyclohexenones. An example is shown in equation (I). 

Trisubstituted six-member carbocycles were also prepared. Condensation of LI with commercial acetoacetanUides 9.14a-f produced, by one-pot Michael addition and Robinson annulation, the cyclohexenone library L4 (7680 members. Fig. 9.11). Noncommercial acetoacetamides Mi, prepared by condensation of diketene 9.15 with 40 primary and secondary amines (structures not shown in the paper), were used as monomers and condensed with a 320-member LI subset to give the expanded cyclohexenone library L5 (12,800 members). Difficulties in preparing extremely large discrete libraries, even using fuUy automated robotic workstations, and the need to diversify the screening set obliged the authors to limit the number of monomers and chalcones for any specific library/scaffold (see also LIO below). 

In addition, Grignard addition to the lactam followed by hydrolysis of the bicyclic lactam affords either 3,4,4-or 2,6,6-trisubstituted 2-cyclohexenones, depending upon the hydrolytic conditions employed (eq 4). ... 

Usually, sulfur compounds are obstacles to catalysis due to catalyst poisoning. In spite of this, Gunnoe and coworkers reported the hydrothiolation of a range of substrates. Hydrothiolation occurred with mono-, di-, and trisubstituted electron-deficient alkenes and styrenes. Anti-Markovnikov regioselectivity was observed in all cases, with [Cu(SR)(IMes)] as the most efficient catalyst The transformation of benzenethiol with cyclohexenone reached full conversion in 5 min with IMes, whereas 8 h were required with the IPr complex. The less steri-cally hindered NHC is more active (IMes > IPr > SIPr) in this transformation. SIPr remained the least efficient which was mainly due to the low solubility of the complex. 

A smdy of the substrate scope revealed that mono-, di-, and trisubstituted vinylcyclopropanes were aU suitable substrates to give cyclohexenones (resulting from cleavage of bond b ) as dominant products in moderate to good yields. The presence of a lot of functional groups such as TBS-protected hydroxyl, Ts- and Boc-protected amino, chloro, toluenesulfonyl, and cyano was well tolerated. It was noteworthy that the [5-1-1] carbonylation reaction could even be conducted catalytically. For example, 34a was produced in 73% yield from 33 in the presence of only 5 mol% Fe(CO)s (Scheme 17.8). 

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