Aryl-Substituted Cyclohexenones

Zimmerman and co-workers - have shown that photolysis of 4,4-diphenylcyclohcx-2-en-l-one gives the following three products  

In addition, it was observed that the sensitized photolysis produced the same distribution of products with the same efficiency (fingerprint characteristic of the triplet state). From quenching studies the specific rate constant for the rearrangement could be obtained. Phenyl migration rearrangement is of intermediate efficiency, interposed between the more efficient and less efficient type A processes (Table 7.4). The type of mechanism proposed for this transformation is as follows  

Photorearrangement of 4-p-cyanophenyl-4-phenylcyclohexene (69) took place mainly byp-cyanophenyl migration. The conclusion could then be drawn that the rearranging excited state is not electron deficient at the )3-carbon atom, since one would not expect a cyanophenyl group to migrate to a positive carbon. The )3-carbon was proposed to have odd electron character  

This also indicates that loss of electronic excitation cannot precede the rate-limiting stage of the reaction otherwise, an electron-ridi oxygen and electron-deficient )9-carbon (70) would lead to reversal of the selectivity  

The triplet decay rates kg for (65) and (69) are so similar that it is not reasonable to suggest that decay is dominated by unsuccessful migration, but must be due to a radiationless transition. 

---

In particular, sulfonylhydrazones are valuable coupling partners in Pd-catalyzed cross-coupling reactions with aryl halides and pseudohalides giving rise to alkenes. As an example, the reaction of a chloroarene with the tosylhydrazone derived from 4-tert-butylcyclohexanone leads to an aryl substituted cyclohexenone (Experimental Procedure below). " " Moreover, the reaction can be conducted directly from the carbonyl... 

When an aryl substituent is placed at C-5 of a 4-substituted cyclohexenone, a new product type containing a cyclobutanone ring is formed. 

Knochel et al. described Pd-catalyzed Negishi cross-coupling reactions between zinc organometallics and aryl iodides in [BMMlM][Bp4]. Scheme 5.2-20 illustrates the reaction for the formation of a 3-substituted cyclohexenone from 3-iodo-2-cyclo-hexen-l-one [82]. 

Protonated phenols and phenol ethers formed in superacids can be trapped by aromatics (benzene, naphthalene, tetrahydroquinoline). The products are either cyclohexenone derivatives301 [Eq. (5.112)] or aryl-substituted phenols. In the reaction of phloroglucinol with benzene, the diphenyl-substituted derivative is the main product [Eq. (5.113)], whereas 1,3,5-trimethoxybenzene gives selectively the monophenyl derivative (80% yield). Protonated dicationic species, such as 76, detected by Olah and Mo302 using NMR, were suggested to be intermediates in these processes. 

Also Pdotalyzed Negishi cross-coupling reactions have been described in ionic liquids. Knochel and coworkers investigated the reaction between organometalhc zinc compounds and aryl iodide in [BMMIM][Bp4] using an ionic phosphine ligand. Scheme 5.3-30 illustrates the reaction for the formation of a 3-substituted cyclohexenone from 3-iodo-cyclohex-2-en-l-one [170]. The reaction vras carried out in an ionic liquid/toluene biphasic system, which allowed easy product recovery from the catalyst by decantation. However, attempts to recycle the ionic catalyst phase resulted in significant catalyst deactivation, after only the third recycle. 

Based on initial studies by Krause and Alexakis [100], the highly enantioselective synthesis of trans-5-aryl-2-substituted cyclohexanones 119 was accomphshed by the conjugate arylation of racemic 6-substituted cyclohexenones 117 (Scheme 8.29) [101]. Although the first step did not proceed in a diastereoselective maimer, only the thermodynamically more stable trans-disubstituted cyclohexanone 119 was obtained after epimerization with NaOEt. 

D.ii,a. Pd-Catalyzed ct-Arylation and a-Alkenylation of Acetal-Protected Enone Derivatives (Protocol I). The reaction of 2-bromo-2-cyclohexenone and 2-iodo-2-cyclohexenone with bis[( )-l-hexenyl]zinc in the presence of 5 mol % of a Pd-PPhj complex in THF at 25 °C gives 2-[( )-l-hexenyl]-2-cyclohexenone in 0% and 31% yield, respectively. In sharp contrast, the corresponding reaction of 3-bromo-2-cyclohexenone provides 3-[( )-l-hexenyl]-2-cyclohexenone in 75% yield, with the balance of the starting bromoenone still remaining unreacted. The sluggish nature of -substitution and the greater instability of a-haloenones are clearly indicated in the competitive experiment summarized in Scheme 18. ... 

In contrast to the substrate-type presented in Scheme 5.6, intramolecular Mizoroki-Heck reactions with cychc alkene moieties are quite common. Negishi and coworkers [21, 29] screened numerous substrates with different substitution patterns, out of which four are shown in Scheme 5.7. Cychzation of aryl iodide 35 proceeded well and furnished tricyclic 36 in good yield, including 10% of a double-bond isomer (not shown) (35 36). Mizoroki-Heck reactions of cyclohexenones 37 and 39 provided 68% and 82% yields respectively and, probably, due to conjugation with the carbonyl group in isomerically pure form (37,39 38,40). The two analogous cyclohexenone derivatives of aryl iodide 35 (not shown) cyclized under identical conditions in 50% and 71% yields respectively. Substrate 41a even allowed for formation of spirocyclic 42a in good yield, yet with poor... 

Treatment of acrolein and cyclohexenone with 2-lithio-2-tri-methylsilyl-1.3-dithiane provides the corresponding unsaturated dithioketene acetals (eq 12). Subsequent exposure to w-butyl-lithium followed by Mel produces protected forms of a, 0-unsatu-rated ketones in almost quantitative yield anion addition occurs distal to the dithiane and alkylation takes place at the dithiane stabilized anion (eqs 13 and 14). Another interesting application is the use of suitably substituted 2-aryl-2-trimethylsily 1-1,3-dithianes as precursors for o-quinodimethanes (eq 15). ... 

---