Limonene hydroboration

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

Hydroboration of limonene with disiamylborane followed by oxidation afforded the isomeric alcohols as 3 2 mixture. These starting materials are utilized in the synthesis of juvabione isomers2101 and in the synthesis of beetle defense substances, chrysomelidial 211), plagiolactone 212) and dehydroiridodial213) (Scheme 6). 

Cyclic hydroboration of ( + )-limonene with thexylborane yields the pure borabicyclic compound (138), which is oxidized to the diol (32 X = OH) or protonol-ysed with acetic acid to yield pure (—)-carvomenthol (32 X = H) after the usual oxidation.227 The treatment of dialkylcyanothexylborates with trifluoroacetic anhydride followed by oxidation as a route to ketones has been used with ( + )-limonene to give the two bridged-ring ketones (139).228... 

A practical synthesis of 1,3-OX AZEPINES VIA PHOTOISOMERIZATION OF HETERO AROMATIC V-OXIDES is illustrated for 3,1-BENZOXAZEPINE. A hydroboration procedure for the synthesis of PERHYDRO-9b-BORAPHENALENE AND PERHYDRO-9b-PHEN-ALENOL illustrates beautifully the power of this methodology in the construction of polycyclic substances. The conversion of LIMONENE TO p-MENTH-8-EN-YL METHYL ETHER demonstrates a regio-and chemoselective method for the PHOTOPROTONATION OF CYCLOALKENES. An efficient method for the conversion of a ketone to an olefin involves REDUCTIVE CLEAVAGE OF VINYL PHOSPHATES. A mild method for the conversion of a ketone into the corresponding trimethylsiloxy enol ether using trimethylsilyl acetate is shownforthe synthesis of (Z)-3-TRIMETHYLSILOXY-2-PENTENE. 

The protonolysis reaction tolerates functionalities such as halide or ether groups in the alkylborane. However, p-dialkylaminoalkylboron compounds undergo elimination to give alkenes under these conditions (see Section 3.10.1.2). ° " Also, systems which are intrinsically labile to either acid or heat, such as some terpenoids, may give problems. For example, enantiomerically pure limonene produces 1 -men-thene which is substantially racemized on hydroboration-protonolysis (Scheme 15). 

Octadiene and higher a,co-dienes with 1 1 HjB-THF leads to polymeric material. Low yields of cyclic products are also obtained in the hydroboration of mixed dienes, e.g., 4-vinylcyclohexene or limonene (see Table 7), but 1,5-cyclooctadiene undergoes cyclic hydroboration in high yield. A mixture of 9-borabicyclo[3.3.1] nonane (9-BBN) and 9-borabicyclo[4.2.1]nonane is formed. Other intermediates are also observed by B NMR. Upon heating, the latter compound is transformed " to the more thermodynamically stable 9-BBN ... 

Another new aldehyde was recently isolated from the oil of Rosa damascena (Bulgarian rose oil), and shown to be menth-l-en-9-al, a mixture of both diastereo-isomers (152) and (153) being present in the natural product. By oxidation of the hydroboration products of (+)-limonene (111) (see also ref. 109), both... 

Limonylborane (LimBH, 1) is best prepared by cyclic hydroboration of limonene with a mono-chloroborane-diethyl ether complex followed by hydridation with lithium aluminum hydride76. 

Both enantiomers of limonene are available naturally. The product obtained from cnantiomeri-cally pure limonene is an epimeric mixture since the hydroboration of the terminal double bond... 

From (+)-limonene, a hydroboration product, limonylborane (32). was obtained and used in asymmetric allylboration reactions, but with less success than the pinene-derived reagents34 (Section D.2.5.2.). 

The "right half of the sesquiterpene (+)-p-selinene (as drawn below) includes (R)-(+)-limonene as a substructure. Retrosynthetic disconnection to (if)-(+)-limonene leads to the intermediate carbenium ions la and lb via 15-nor-ll-eudesmen-4-one (carbonyl alkenylation) and 15-nor-13-chloro-2-eudesmen-4-one (dehydrogenation, protective masking of the double bond in the side chain). These carbenium ions arise from (if)-9-chloro-p-menth-l-ene and the acylium ion Ic (synthone) originating from 3-butenoic acid as reagent (synthetic equivalent). (i )-/7-Menth-l-en-9-ol, on its part obtained by hydroboration and oxidation of (if)-(-l-)-limonene, turns out to be the precursor of the chloromenthene. 

Thus, the first step of a stereoselective synthesis of p-selinene reported by Mackenzie, Angelo and Wolinski involves hydroxylation of the C-8-C-9-double bond of (i )-(+)-limonene by hydroboration with diborane and subsequent... 

The syntheses in Schemes 10.6,10.7, and 10.10 are stereoselective. In Scheme 10.6, the starting material is an optically active terpene, limonene. The chiral center leads to modest stereoselectivity in the hydroboration (step A), there is a 3 2 preference for the desired stereoisomer,- and the intermediate is obtained stereochemically pure after crystallization of a solid derivative. These chiral centers are not involved in any of the further transformations, so the stereochemistry is established early in the synthesis, and all further reactions are free of complications due to separation of stereoisomers. In Scheme 10.7, the stereochemistry is controlled by virtue of the bicyclic nature of the intermediate Diels-Alder adduct. The isomeric... 

Baker s yeast based asymmetric C=C bond hydrogenations have been exploited for the synthesis of several terpenes and sesquiterpenes, which are two important classes of naturalproducts.Thereductionof(R)-and(S)-23(Scheme3.5),easily prepared from the (R)- and (S)-enantioforms of Umonene 24, gives access to each diastereoisomer ofp-menth-l-en-9-ol 25 in >60% yields and vdth a very high optical purity [54]. This procedure compares well in terms of simplidty, stereoselectivity, and yield to other reported syntheses based on the hydroboration or hydroalumination of C(8)=C(9) double bond of limonene followed by fractional crystallization of nitrobenzoate... 

---