Cyclohexane carbaldehyde

A recent example where Co2(CO)8 serves as a precatalyst is in the preparation of linear and branched aldehydes via propylene hydroformylation in supercritical C02 (93-186 bar 66-108 °C). Cyclohexane carbaldehyde is produced from cyclohexene using Co2(CO)8 and an acid RCOOH, or else is successful with another established Co catalyst, Co(OOCR)2, assumed to form in situ in the former case. Oligomerization of aldehydes such as n-butanal is achieved with Co2(CO)6L2 as catalyst (L = CO, PR3).1364... 

The ring expansion of 1-alkoxy-functionalized cyclohexane carbaldehydes (Scheme 9.42) was investigated by Kuwajima s group with 50mol% of FeCl3 to yield the ring expansion products 53/54 in 89% yield as a 14 1 mixture of constitutional isomers [100]. 

Scheme 9.42 Ring expansion of cyclohexane carbaldehyde derivatives.

The search for other amino acid-based catalysts for asymmetric hydrocyanation identified the imidazolidinedione (hydantoin) 3 [49] and the e-caprolactam 4 [21]. Ten different substituents on the imide nitrogen atom of 3 were examined in the preparation, from 3-phenoxybenzaldehyde, of (S)-2-hydroxy-2-(3-phenoxy-phenyl)acetonitrile, an important building block for optically active pyrethroid insecticides. The N-benzyl imide 3 finally proved best, affording the desired cyanohydrin almost quantitatively, albeit with only 37% enantiomeric excess [49]. Interestingly, the catalyst 3 is active only when dissolved homogeneously in the reaction medium (as opposed to the heterogeneous catalyst 1) [49]. With the lysine derivative 4 the cyanohydrin of cyclohexane carbaldehyde was obtained with an enantiomeric excess of 65% by use of acetone cyanohydrin as the cyanide source [21]. 

In 2000, Kagan and Holmes reported that the mono-lithium salt 10 of (R)- or (S)-BINOL catalyzes the addition of TMS-CN to aldehydes (Scheme 6.8) [52]. The mechanism of this reaction is believed to involve addition of the BI NO Late anion to TMS-CN to yield an activated hypervalent silicon intermediate. With aromatic aldehydes the corresponding cyanohydrin-TMS ethers were obtained with up to 59% ee at a loading of only 1 mol% of the remarkably simple and readily available catalyst. Among the aliphatic aldehydes tested cyclohexane carbaldehyde gave the best ee (30%). In a subsequent publication the same authors reported that the salen mono-lithium salt 11 catalyzes the same transformation with even higher enantioselectivity (up to 97% Scheme 6.8) [53], The only disadvantage of this remarkably simple and efficient system for asymmetric hydrocyanation of aromatic aldehydes seems to be the very pronounced (and hardly predictable) dependence of enantioselectivity on substitution pattern. Furthermore, aliphatic aldehydes seem not to be favorable substrates. 

These reductions can be combined with other transformations as exemplified by cyclopropane 120, which has been converted to the nitrile 122, the spiro lactone 123, and the functionalized spiro tetrahydrofuran 121 61). All products are eventually derived from cyclohexane carbaldehyde. 

Ozonolysis-reduction of an unknown alkene gives an equimolar mixture of cyclohexane-carbaldehyde and butan-2-one. Determine the stmcture of the original alkene. 

It reacts to the industrially desired 2,2,3,6-tetramethyl-cyclohexane-carbaldehyde 19 in the presence of acidic catalysts beside many other products. 

In 1993 Corey et al. [60] reported a new enantioselective method for synthesis of chiral cyanohydrins [61] from aldehydes and trimethylsilyl cyanide (TMSCN) by the use of a pair of synergistic chiral reagents. Reaction of cyclohexane carbaldehyde 78 and trimethylsilyl cyanide (TMSCN) 79 in the presence of 20 mol % chiral magnesium complex 80 afforded the cyanohydrin TMS ether 81 in 85 % yield with 65 % ee. This modest enantioselectivity was fiirther enhanced to 94 % ee by addition of a further 12 mol % of the bis(oxazoline) 70 (Sch. 34). 

The efficiency of this approach is seen in a prompt reductive coupling of sulfide 204 with cyclohexane carbaldehyde to afford C-glycosyl derivative 205. This was applied to a fast synthesis of the same disaccharidic component of the sialylTn antigen [96] (O Scheme 43). 

Research in the laboratory of R.L. Danheiser has shown that allenylsilanes can be reacted with electrophiles other than enones, such as aldehydes and A/-acyl iminium ions to generate oxygen and nitrogen heterocycles." Aldehydes can function as heteroallenophiles and the reaction of C3 substituted allenylsilane with the achiral cyclohexane carbaldehyde afforded predominantly c/s-substituted dihydrofurans. 

Isomerization of 4,4,5,8-Tetramethyl-l-oxa- piro 2.5 octane - 4,4,5,8-Tetra-methyl-l-oxaspiro[2.5]octane (1) is obtained in a multistep synthesis from easily available ( —)-(5)-P-citronellol or (+)-/ -pulegone. It reacts to the industrially-desired 2,2,3,6-tetramethyl-cyclohexane-carbaldehyde (2) (Figure 5) in the presence of acidic catalysts beside many other by-products. 

Preparation of Z-propenylzinc bromide (281) via Br/Li exchange reaction and its asymmetric addition to cyclohexane carbaldehyd ... 

When the -CHO group is a substituent on a ring, we use the term carbaldehyde. Thus, 4.36 is cyclohexane carbaldehyde and 4.37 is benzene carbaldehyde, usually contracted to benzaldehyde ... 

Acetophenone and cyclohexane carbaldehyde simply exchange the a-hydrogens ... 

This reaction is restricted to derivatives of N-benzylideneaniline since cyclohexane carbaldehyde or pivaldehyde with aniline give the product in less than 10% yield. More surprisingly, the reaction of acylzirconocene chloride 38 with imine proceeds with a Bronsted acid, even in aqueous media. Although, the hydrolysis of acylzirconocene into aldehyde is a well-known process (see Scheme 12.22), the reaction with N-phenyl imine is much faster. Under 20mol% HCl/THF, the... 

---