Unexpected formation of bicyclo[3.3.1]nonenyl methanesulfonate from tricyclo[ 4.3~0.0 2 , 9 ]nonan-8-olt

Attempted methanesulfonylation reaction of the tricyclo[4.3.0.0 2•9 ]nonan-8-ol 8 under standard conditions led to the selective cleavage of the CrC 9 cyclopropane bond resulting in the formation of bicyclo[3.3.1]non-2-en-9-yl methanesulfonate 17 in stead of the expected methanesulfonate 9 of the starting alcohol or the fragmentation product bicyclic diene 10.

The bicyclo [3.3.1]nonane ring system 1 has received considerable attention from both synthetic 1 as well as theoretical chemists 2 . The bicyclic framework 1 is present as part structure in several natural products, particularly in alkaloids and terpenoids such as limonoid xylocaripin, sesquiterpenes clovanediol, upial, trifarienols etc. In addition, bicyclo [3.3.l]nonanes have also been utilized as synthons for the construction of a variety of complex ring systems, enroute to natural products 3 .4.
The synthetic utility of reactions involving long-range orbital interaction over more than three a-bonds is not fully exploited. One of the important reactions that involves orbital interactions over more than three a-bond is the heterolytic Grob fragmentation 5 . Molecules containing electro fugal as well as nucleofugal moieties spaced with two carbons undergo regulated cleavage (fragmentation) into three fragments. In the general formulation (eq. I), A-B denotes a electrofugal group, which leaves as A-B without the bonding electron pair. The middle group C-D affords the unsaturated fragment C=D, while the nucleophilic group X leaves with bonding electrons. There are three different mechai1isms possible for such reactions, although the structure, electronic req~irements and the number of bonds broken are same, the sequence with which bond rupture occurs may be different. Quite obviously in polycyclic systems, this kind of fragmentation leads to cleavage of one or two rings. During our exploratory studies towards the development of a methodology for the enantiospecific synthesis of pinguisanes 6 , we have come across an interesting fragmentation reaction which resulted in the enantiospecific generation of bicyclo[3.3.1 ]nonanes 7 . Attempted synthesis of the methanesulfonate 2 starting from the tricyclic alcohol31ed to a 1 ,4-homoelimination product 4, similar to the Grob fragmentation. Formation of the bicyclic compound 4 can be rationalized either via a E 2 -type concerted 1,4homoelimination similar to the Grob fragmentation as shown in 5 or via the corresponding cyclopropylmethyl carbonium ion 6 (E 1 -type) of the methanesulfonate 2. In an attempt to establish the mechanism, the reaction was also carried out with the epimeric exo-alcohol 7, obtained from 3 employing a Mitsunobu protocol, which also resulted in the formation of the same bicyclic diene 4, suggesting the intermediacy of the cyclopropylmethyl carbonium ion in the transformation of 2 ~ 4. The reaction was investigated with a reasonable number of l-methyltriayclo[4.3.0.0 2 • 9 ]nonan-8ols and found to be general.
Subsequently, to investigate the role of the angular methyl group in the fragmentation reaction, the reaction was explored with the tricyclic alcohol 8, which lacks a methyl group on the C-1 carbon and contains a methyl group at C-6 carbon. As the methyl g~oup at the C-1 position is absent in the tricyclic alcohol 8, it was anticipated that it will generate either the simple methanesulfonate 9 or the fragmentation product bicyclo cyclopropanation 9 based methodology as depicted in Scheme 1. Thus, thermal activation of the allyl alcoholll with triethyl orthoacetate and a catalytic amount of propionic acid furnished the ester 12 in 77% yield. Hydrolysis of the ester 12 with sodium hydroxide in aqueous methanol furnished the acid 13. Reaction of the acid 13 with oxalyl chloride in benzene at room temperature furnished the acid chloride 14, which on treatment with an excess of ethereal diazomethane generated the diazo ketone 15. Copper sulfate catalysed decomposition of the diazoketone 15 followed by intramolecular cyclopropanation of the resultant ketocarbenoid generated the tricyclic ketone 10 16 in a stereospecific manner. Reduction of the tricyclic ketone 16 with sodium borohydride in methanol and tetrahydrofuran at ice temperature furnished a 6 : 1 mixture of the tricyclic alcohol 8 in 88% yield, whose structure rests secured from the spectral data. Presence of a peak at 151 (C 10 H 15 0, M+-1) in the mass spectrum and a strong absorption band at 3400 cm-1 due to the hydroxy group in the IR spectrum, presence of a ddd 1016 signal at 4.81 (J 12.6, 6.3 and 2.7 Hz) due to the methine attached to the hydroxy group, a singlet at 1.14 due to the tertiary methyl group for the major isomer in the 1 H NMR spectrum established the structure of the alcohol 8, which was further confirmed by the 13 C NMR spectrum.
Reaction of the alcohol 8 with methanesulfonyl chloride in methylene chloride and an excess of pyridine, in contrast to the expected diene 10 or the simple methanesulfonate 9, furnished an olefin containing methanesulfonate 17 in 65% yield, whose structure was deduced from its spectral data.
In the IR spectrum presence of absorption bands at 3020 and 1560 cm-1 due to olefin and at 1350 and 1170 due to a sulfonate group revealed formation of a rearranged methanesulfonate. A solution of3-methylcyclohexenolll (7.4 g,,67 mmol), triethyl orthoacetate (15 ml, 82 mmol) and propionic acid (catalytic) in toluene (15 ml)was placed in fourCarius tubes under nitrogen atmosphere and heated at 180° for four days. The Carius tubes were cooled and the contents were pooled. The reaction mixture was diluted with ether, washed with aqueous NaHC0 3 solution followed by brine and dried (Na 2 S0 4 ). Evaporation of the solvent and purification of the residue over a silica gel column using ethyl acetatehexane (l : 40) as eluent furnished the ester 12 (9.45 g, 77%) as colourless oil 11

2-( 1-Methylcyclohex-2-en-1-y/)acetic acid (13) :
To a magnetically stirred solution of the ester 12 (5.25 g, 28.8 mmol) in methanol (20 ml) was added a solution of sodium hydroxide (6 gin 20 ml water) and the reaction mixture was refluxed for 7 h. It was then cooled and washed with methylene chloride (10 ml). The aqueous portion was acidified with cone. HCI and extracted with methylene chloride (3 x 15 ml). The methylene chloride extract was washed with brine and dried (Na 2 S0 4 ). Evaporation of the solvent furnished the acid 13 ( 4. To a magnetically stirred, refluxing suspension of anhydrous copper sulfate (8 g) in dry cyclohexane ( 150 ml) was added, a solution of the diazoketone 15 (2.00 g, 11.2 mmol) in cyclohexane (20 ml) dropwise over a period of 30 min and refluxed for 5 h. The reaction mixture was cooled and filtered through a sintered funnel. Evaporation of the solvent and purification of the residue over a silica gel column using ethyl acetate-hexane (1 : 10) as eluent furnished the tricyclic ketone 16 (927 mg, 55%) as oil 10  To an ice-cold magnetically stirred solution of the tricyclic ketone 16 ( 100 mg, 0.67 mmol) in THF (5 ml) and methanol (5 ml) was added sodium borohydride (12.7 mg, 0.34 mmol) and stirred for 30 min. The solvent was evaporated under reduced pressure, the residue was taken in methylene chloride, washed with dilute HCI followed by brine and dried (Na 2 S0 4 ). Evaporation of the solvent and purification of the residue over a sili~a gel column using ethyl acetate-hexane (1 : 10) as eluent furnished a 6 : I epimeric mixture of the tricyclic alcohol 8 (89 mg, 88%