Aldehydes isoprenylation

Brown s synthesis of 34 and 35 utilized -2 -isoprenyldi-Z-isopinocam-pheylborane B as a reagent for asymmetric isoprenylation of aldehydes as shown in Scheme 50 [76]. 

A striking example of the power of A -heterocyclic carbene (NHC)-bearing catalysts with sterically demanding substrates was disclosed by Chavez and Jacobsen, " who presented a route to several iridoid natural products, exemplified by the enantio- and diastereoselective synthesis of boschnialactone 31 outlined in Scheme 5. Chiral aldehyde 27, available from citronellal by Eschenmoser-methylenation in a single step, reacted despite the presence of an isoprenyl moiety and a gi OT-disubstituted double bond, in the presence of catalyst C smoothly to form... 

The activated zinc obtained by electrochemical reduction of Zn2+ in dimethylformamide has been used for the isoprenylation of aldehydes and ketones. This has been reported by Tokuda and coworkers (equation 4)10. 

The isoprenylation of isovaleraldehyde led to the product in 68% isolated yield, higher than with a conventional procedure using zinc dust in DMF, or refluxing THF. The same procedure was used for the coupling reaction of allylic bromides with aldehydes and ketones, via the preliminary formation of organozinc compounds coming from the reaction between the electrolytic zinc and allylic bromides12. 

This procedure was used in the isoprenylation of aldehydes and ketones4 (Equation 8.4) ... 

Isoprenylation of carbonyl compounds. In the presence of TiCl, 1 can react as an allylsilane with acetals and acid chlorides (7, 370-371) to give isoprenylated compounds in generally satisfactory yields. Yields with aldehydes tend to be low. Isoprenylation of carbonyl groups is best effected with catalysis with tetrabutylammonium fluoride or io-dotrimethylsilane (10, 216). 

In the second step, aldehyde 50 is subjected to a Grignard reaction with isoprenyl Grignard reagent 53 which can be readily obtained from 2-bromopropene (51) via halogen-metal exchange using tert-butyllithium and subsequent transmetallation with magnesium bromide. 

The addition of isoprenyl Grignard reagent 53 to aldehyde 50 proceeds with chelation control (via transition state A) to favor the formation of allylic alcohol 23 with the (16 S)-configuration at the newly formed stereogenic centre. Alcohol 23 is obtained in 63 % yield as an inseparable 86 14 mixture in favor of the desired (16 S)-diastereomer. 

Brown, H. C., Randad, R. S. B-2 -lsoprenyldiisopinocampheylborane an efficient reagent for the chiral isoprenylation of aldehydes. A convenient route to both enantiomers of ipsenol and ipsdienol. Tetrahedron Lett. 1990, 31,455-458. 

Several bacterial species produce C45 and C50 carotenoids which contain one or two extra isoprenyl groups. Although their biosynthesis has not been studied, it is probable that instead of proton-initiated cyclisation at the polyene termini, attack by dimethyl allyl pyrophosphate results in substances such as the symmetrical decaprenoxanthin (P439) (68). The stereochemistry of the isolated acyclic double bond was shown to be trans by the n.m.r. spectrum of the corresponding aldehyde. Other carotenoids present in Flavobacterium... 

Typical of allylboranes, B-isoprenyl-9-BBN reacts with acetaldehyde with allylic rearrangement to provide the borinate intermediate via a six-mem-bered transition state [43]. The alkaline hydrogen peroxide oxidation of this intermediate affords the desired 4-methylene-5-hexen-2-ol (Eq. 24.20). Table 24.20 [41] summarizes the results of representative aldehydes with B-isopre-nyl-9-BBN. 

FTiR (wavenumber-assignment) cm V- C=0 1690 (carboxyl), 1720 (aldehyde), 1745 (ketone) 855 -frans-isoprenyl unit ... 

These catalytic enantioselective polyene cyclizations have been accomplished through the use of substrates with the appropriate functional groups on the reactive sites, such as aldehydes and hydroxylactams. Therefore, these methods cannot be applied to the enantioselective cyclization of simple isoprenoids with a terminal isoprenyl group. 

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